Sleep Medicine Reviews 16 (2012) 117e127

Contents lists available at ScienceDirect

Sleep Medicine Reviews

journal homepage: www.elsevier.com/locate/smrv

CLINICAL REVIEW

Sleep disturbances in children with multiple disabilities

Anna-Lena Tietze a, *, Markus Blankenburg a, d, Tanja Hechler a, Erik Michel b, Michelle Koh c,
Bernhard Schlter d, Boris Zernikow a
a
Vodafone Foundation Institute and Chair for Childrens Pain Therapy and Paediatric Palliative Care, Witten/Herdecke University, Childrens Hospital Datteln,
Dr. Friedrich Steiner Str. 5, 45711 Datteln, Germany
b
Childrens Hospital, Hospital Friedrichshafen, Friedrichshafen, Germany
c
Great Ormond Street Hospital for Children NHS Trust, London, UK
d
Childrens Hospital Datteln, Witten/Herdecke University, Germany

a r t i c l e i n f o s u m m a r y

Article history: Introduction: Although sleep disturbances in disabled children are of central clinical importance, there is
Received 10 October 2010 little research on that topic. There are no data available on frequency, severity or aetiology of sleep
Received in revised form disturbances and related symptoms in this specic patient group.
22 March 2011
Objective: To review the current state of research and outline future research objectives.
Accepted 22 March 2011
Available online 26 May 2011
Methods: We searched international scientic databases for relevant publications from 1980-2009. From
all papers qualifying for further analysis we retrieved systematic information on sample characteristics,
sleep assessment tools and their test quality criteria, and core ndings.
Keywords:
Agitation
Results: 61 publications including 4392 patients were categorized as mixed (reporting on heteroge-
Children with multiple disabilities neous diagnoses), or specied papers (specic diagnoses) based on international classication of
Sleep disturbances diseases (ICD) 10 classication. To assess sleep disturbances, most authors relied on subjective instru-
Sleep questionnaires ments with poor psychometric quality. Mean prevalence of sleep disturbances was 67% (76%,mixed
group; 65%, specied group). In children suffering severe global cerebral injury, the prevalence of sleep
disturbances was even higher (>90%). The most frequent symptoms were insomnia and sleep-related
respiratory disorders. Some of these symptoms were closely associated with specic medical syndromes.
Conclusion: There is an urgent need for sleep disturbance assessment tools evaluated for the patient
group of interest. By use of validated assessment tools, patient factors, which may be crucial in causing
sleep disturbances, may be investigated and appropriate treatment strategies may be developed.
2011 Elsevier Ltd. All rights reserved.

Introduction
Since the 1980s, sleep disturbance in healthy children has been
a signicant issue in paediatrics.1,2 With a prevalence of 25e40%,
sleep disturbance is frequent3e6 and has numerous negative effects
on physical symptoms, cognitive development, and daytime
behaviour.4,7e9
Clinical practice as well as research data show that sleep
disturbance is not only a problem in healthy children requiring
treatment, but is particularly signicant in children with physical
and mental disability.10 The more pronounced the disabilities in
these patients (co-existence of impairments), the more frequent
Abbreviations: ICSD, international classication of sleep disorders; PSG,
polysomnography; SBD, sleep-related breathing disorder; SD, standard deviation;
a, Cronbach's alpha.
* Corresponding author. Tel.: 49 2363 975 180; fax: 49 2363 975 181.
E-mail address: a.tietze@kinderklinik-datteln.de (A.-L. Tietze).
and severe are the sleep disturbances and the less likely is a spon-
taneous symptom relieve.6,11 Clinical studies and data on frequency,
type and symptoms (e.g., daytime restlessness) of sleep disturbance
are lacking in this patient group.6,10e13 Furthermore, there is
controversial discussion about the aetiological factors, which are
responsible for the high prevalence of sleep disturbance in children
with multiple disabilities. Some authors assumed factors depend-
ing on the specic diagnosis (e.g., brain abnormality)14e17 or
specic factors inherent to the main diagnosis (e.g., spasticity).18e20
Since diagnosis of the underlying pathophysiology is not possible in
about 50% of children suffering from severe motor or psychomotor
life-limiting disease,21 the feasibility of exploring the impact of the
underlying disease as an aetiological factor for sleep disturbance
may be disputed. However, information on prevalence, type and
severity of sleep disturbance with respect to the main diagnosis is
helpful for clinical practice.
In addition, there are other factors secondary to the disease
(e.g., pain), adverse effects of medication, psychosocial factors

1087-0792/$ e see front matter 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.smrv.2011.03.006
118 A.-L. Tietze et al. / Sleep Medicine Reviews 16 (2012) 117e127
Glossary
Disability, is the functional inability of an individual to
perform any activity in the manner or within the range
considered normal for any human being. It is a restriction
of activity or ability as a result of impairment and interferes
in the performance of daily activities by an individual.
Multiple disabilities, is the co-existence of two or more
disabilities such as intellectual impairment and physical
handicap.
Specified group: sample with specific disease
Mixed group: sample with heterogeneous diseases
(e.g., parental distress and behaviour) or environmental factors
(e.g., sleep environment, parentechild interaction) which nega-
tively impact on the quality of sleep.3,17,22 The diminished sleep
quality may further lead to increased daytime drowsiness, rest-
lessness, and aggravation of the underlying disease (i.e., lower
seizure threshold in epileptic disorders, increased level of distress,
or impaired regenerative processes). These processes creating
a vicious cycle with ever increasing sleep disturbance.
One reason for the lack of sleep research in children with
multiple disabilities may be the difculty in selecting a suitable,
validated instrument capable of reliably assessing sleep distur-
bance in this patient group. Most sleep assessment tools have been
designed for use in healthy children.23e25 However, their use in
children with multiple disabilities is questionable given the clinical
features and the complexity of disabilities and symptoms of these
children, which did not allow their parents to evaluate some sleep
disorders (e.g., sleep talking, somnambulism, nightmare). Addi-
tionally, questionnaires that have been designed for use in healthy
children do not consider factors that disrupt sleep which are
inherent to the main diagnosis (e.g., waking for treatment, spasm,
etc.) in children with multiple disabilities.24,26
The aim of this paper is to review the literature on prevalence,
symptoms and assessment of sleep disturbance in children with
multiple disabilities.
The following questions were addressed by a comprehensive
literature review:
1) How frequent and what type of sleep disturbance occurs in this
specic group of patients with respect to the underlying
pathology of diseases? We depicted frequency and type of
sleep disturbance in samples with heterogeneous diagnoses
(mixed group) and in samples with specic diagnosis (specied
group).
2) Which assessment tools have been implemented and what is
their psychometric quality?
Methods
Data sources
To identify the children suffering from various life-limiting
diseases from published papers, we used the following search
terms: cerebral haemorrhage, ischemia or inammation; chronic
disease; chronic metabolic or neurodegenerative disease; intellec-
tual or physical disability; sleep; sleep disorder; sleep problem; sleep
disturbance; syndrome; neurodevelopmental disorder; neuromus-
cular disease. We systematically searched the online databases
EBSCOhost, Psyndex, Pubmed and Web of Science (Thompson/
ISI) for relevant publications. All studies had to have been pub-
lished in English or German. We dened the following inclusion
criteria: i) type of study: prospective or retrospective clinical
study, randomized controlled study, controlled clinical study,
review article, comment, meta-analysis, practice guideline, orig-
inal work. ii) topic of the study: sleep or sleep disturbances; iii)
age range of the study population: ranging between birth and
young adulthood; iv) clinical characteristics of the study pop-
ulation: children or adolescents diagnosed with severe motor or
psychomotor life-limiting disease with associated multiple
disabilities. Publications on paediatric patients with a medical
condition as a primary diagnosis and associated psychiatric
symptoms (such as mental retardation, autism) were included in
the review. Letters to editors or case reports were not included
into the present review, nor were publications on paediatric
patients with primarily psychiatric and behavioural disorders
(e.g., Attention decit disorder, developmental disorders).
Procedure of study allocation
Based solely on title and abstract, two of the authors (A.T., M.B.)
independently classied each publication as being eligible for the
review or not. We also browsed the reference lists of the included
publications for further studies, and these were then allocated to
the review based on the dened inclusion criteria. In addition, we
included two very important monographs on sleep disturbances in
children with life-limiting chronic diseases.8,27
All publications were classied as either included, uncertain",
or excluded. If the classication required more information than
available from title or abstract, articles were read in full. Kappa
statistics were used to estimate inter-rater-agreement.28 Any clas-
sication discrepancies were discussed between the two classifying
authors in order to nd consensus. An independent arbitrator (T.H.)
settled any conicting decisions. All publications qualifying as
uncertain were repeatedly categorized in order to reach a denite
decision of included or excluded.
Mixed and specic group
Publications qualifying for in-depth analysis were categorized as
reporting either on mixed or specied patients. The mixed
group comprised studies reporting on heterogeneous diseases;
those studies mostly aimed to deliver a general view on sleep
disorders in children or adolescents suffering severe and chronic
primary diagnoses. The specied group comprised publications
on sleep disturbances in specied patient groups and diseases
based on international classication of diseases (ICD) 10 classi-
cation29 such as syndrome, neurodegenerative or metabolic
disease, neuromuscular disorders, cerebral palsy and other cerebral
disorder/injuries.
Outcome ndings
Finally, all articles qualifying for further analysis underwent
systematic information extraction on main outcome ndings with
respect to the diagnostic features of sleep disturbance: i) preva-
lence of sleep disturbance, ii) symptoms of sleep disturbance, iii)
pathophysiology.
For the presentation of the outcome ndings, we initially
highlight results independently of aetiological diagnosis, followed
by a disease specic analysis. As already mentioned above for our
disease specic analysis strategy, we distinguished between ve
aetiological groups: i) syndrome, ii) neurodegenerative or meta-
bolic disease, iii) neuromuscular disorder, iv) cerebral palsy and v)
other cerebral disorder/injury.
 A.-L. Tietze et al. / Sleep Medicine Reviews 16 (2012) 117e127 119

Results disturbance in specic main diagnoses groups (e.g., cerebral palsy,

Data collection
The database search yielded a total of 294 publications. In
a rst step, after checking titles and abstracts, 80/294 publica-
tions could be included. Publications had to be excluded because
of reporting on patient samples that did not full our patient
criteria (adults; healthy children; not matching diagnoses like
psychiatric disorder or idiopathic epilepsy), or because they
did not focus on sleep and sleep-associated disturbance (Fig. 1,
Study chart). Inter-rater-agreement was acceptable (Kappa, 0.59;
P < 0.05).28
68 additional articles depicted from reference lists of publi-
cations already identied were included after checking inclusion
criteria. Accordingly, full texts of a total of 148 publications
were investigated with regards to sample characteristics, main
outcome ndings, and assessment method(s). From those arti-
cles, 92 publications were on sleep and sleep-associated prob-
lems or sleep disturbances in children with severe and multiple
disabilities. 31 papers were reviews, narrative reviews, or
comments. Those 31 publications had to be excluded for analysis
of outcome ndings, leaving a total of 61 articles for in-depth
analysis.
Publication characteristics
There were 10 publications on sleep disturbance in mixed
samples of children suffering multiple disabilities.2,10,13,19,30e35 80%
reported outcome ndings of heterogeneous samples independent
of main diagnosis and did not differentiate between sleep
syndrome).2,10,13,19,32e35
51 publications reported on sleep disturbance in specied
patient groups. 26 of those publications investigated sleep distur-
bance in specic syndromes of childhood or adolescence such as
Prader Willi syndrome, cri du chat syndrome, Angelman syn-
drome.18,36e60 There were eight articles on sleep disturbance in
children with neurodegenerative or metabolic disease,61e68 seven
articles on sleep disturbance in children with neuromuscular dis-
orders,69e75 three articles on sleep disturbance in children with
cerebral palsy,16,76,77 and seven articles on sleep disturbance in
children with disabilities of other origin (e.g., cerebral inamma-
tion, drowning, or mechanical trauma).78e84 Most of those seven
studies attributed the reported sleep disturbance to mild brain
trauma (N 3).80,81,83
Table 1 further characterizes the articles qualifying for in-depth
analysis. The articles originated from 14 countries. Most studies
stemmed from the USA and UK, contributing half the studies (N 31;
51%). There were 3 articles on sleep disturbance from Germany.41,72,73
While most samples comprised clinical patients (N 37 articles;
62%), there were also studies which recruited their patients from
self-help groups or societies for families with ill children (N 14
articles; 23%), or from surveys in school or community (N 9
articles; 15%).
The 61 studies comprised a total of 4392 children and adoles-
cents. In the mixed group, median sample size was 105
(mean 129; SD 99). In the specied group, median sample
size was 34 (mean 60; SD 84). The study with the largest
sample size was an epidemiologic investigation, analyzing the sleep
behaviour of more than 500 patients suffering from neuromuscular
disorders.69

Citations identified from search of studies excluded

electronic data bases
duplicate 35
N = 294 articles case study / N < 3 11
inappropriate main diagnosis 41
inappropriate topic 55
inappropriate age-group 39
healthy sample 33

Articles retrieved for Total 214

potential inclusion
N = 80 articles depicted from reference lists

N = 68

studies excluded
Articles retrieved for
potential inclusion commentary / not peer-reviewed 5
N = 148 case study / N < 3 1
healthy sample 20
inappropriate main diagnosis 16
inappropriate topic 10
N = 92 inappropriate age-group 4

Total 56

excluded reviews

Articles for inclusion in analysis of N = 31

outcome findings
N = 61

Fig. 1. Study chart.

120 A.-L. Tietze et al. / Sleep Medicine Reviews 16 (2012) 117e127
Outcome ndings
Prevalence
51 of the studies reported prevalence data for sleep disturbance
(see Table 2). According to our classication of the studies, there
were ten studies classied as mixed and 42 articles reporting on
children with specic disorders. In all the studies, there was a high
prevalence of sleep disturbance (mean, 67%; SD, 22.7), which were
individually dened in each study. Independent of main diagnoses,
74.5% of the studies reported the prevalence of sleep disturbance as
> 50%. In half of the studies (N 23), the prevalence exceeded 70%.
According to data from mixed samples, 54e99% (mean, 76%) of
the children with life-limiting illness show clinically signicant
sleep disturbance.2,10,13,19,31e34 In specied samples, the prevalence
ranged between 28 and 100% (mean, 65%) (see Table 2).
As shown in Table 2, prevalence of sleep disturbance does not
vary much between patient groups. There is more variability within
the same type of patients as measured by different studies. The
highest prevalence of sleep disturbance, and lowest variability, is
found in children suffering Smith Magenis syndrome,49,53,55,60
hypoxic-ischemic encephalopathy, or CNS inammation.82 A
prevalence >50% is found in the paediatric population suffering
Angelman syndrome, cerebral palsy, or neuromuscular/neurode-
generative disorders. In traumatic brain injury, the prevalence of
sleep disturbance ranges between 31 and 76%80,81,83 and is slightly
lower in children with Downs syndrome.43,45,56
Symptoms
In 80% (N 49 articles) of the studies, data on the presence of
various types of sleep disturbance and symptoms of disturbed sleep
are given. The symptoms were categorized into the six main classes
according to the international classication of sleep disorders
(ICSD)-2 (see Table 3). Information on the underlying pattern of
sleep disorders was not analyzed because of limited number of
studies and lack of detailed information in the articles.
As shown in Table 3, the most frequent sleep disturbance was
difculty in initiating or maintaining sleep (insomnia; N 36 arti-
cles; 73%), followed by sleep-related respiratory disorders (SBD;
N 20 articles; 41%). 13 studies reported on reduced total sleep
duration.10,13,33,37e40,42,49,55,56,58,60 One study reported an extended
total sleep duration.44 73% of the studies reported on the presence of
more than two symptoms of sleep disturbance, while 56% reported
on the simultaneous presence of three or more symptoms. The
number of ICSD-2 symptoms per patient ranges between one and six.
The most inuential criteria for assessing the clinical signi-
cance of any sleep disturbance, or the need for treatment, is its
impact on daily constitution.85 24% of the studies report on daytime
sleepiness or naps in addition to the disturbance at
night.13,16,30,34,43,47,49,54,55,60,61
The scarce electroencephalographic data available show
changes in sleep architecture, diminished and shortened REM
episodes, reduced eye movements, a prolonged time span to rst
REM episode, an increased proportion of sleep stage 4 as well as
peculiarities with respect to shape and distribution of sleep
spindles.45,51,58e60,76,82
Relationship between symptoms and main diagnosis (specied
groups)
Syndromes. Twenty-three studies investigated the correlation
between specic medical syndromes and sleep disturbance.
Symptoms most often found were difculties in initiating or main-
taining sleep, sleep-related respiratory problems or parasomnias
(see Table 4). Obviously, some of the sleep disturbance was closely
associated with some specic syndromes. Difculties in initiating or
maintaining sleep are rather unspecic, whilst sleep-related
respiratory or movement problems, parasomnias and daytime
sleepiness are frequently seen in only a few syndromes. Children
with Angelman syndrome often reported difculties in initiating or
maintaining sleep, repeated awakening during the night, sleep-
related movement disorders and parasomnias.42,44,51 Prader Willi
syndrome is characterized by excessive daytime sleepiness, daytime
naps or sleep-related respiratory problems.41,52,57,59 By contrast,
girls suffering from Rett syndrome showed regular, continuous
breathing during sleep, but decreased percentages of rapid-eye-
movement sleep, decreased total night time sleep and more
daytime naps.37e40 In Williams syndrome,36,47 Cri du chat
syndrome,50 Smith Magenis syndrome,49,55 Cornelia de Lange
syndrome18 and Downs syndrome,30,43,45,48,56 sleep-related prob-
lems are closely associated to individual syndromes (see Table 4).
Neurodegenerative and metabolic disorders. Eight studies investi-
gated sleep disturbance in children with neurodegenerative or
metabolic disorders. In this patient group, sleep disturbance had
a severe negative impact on daily life.61,62,64 Five of the studies
presented a detailed analysis of the sleep-related symp-
toms.61,62,65,67,68 Most frequently, there were difculties initiating or
maintaining sleep,61,62,65,68 impaired circadian rhythm,61,62,68 par-
asomnia,61,68,87 or obstructive apnoea67 caused by degenerative
processes of CNS grey or white matter, especially functional
impairment of the brain stem or mesencephalon, resulting in
impaired secretion patterns of neurotransmitters (serotonin, GABA),
melatonin or cortisol.87,88
Neuromuscular disorders. Seven studies reported on sleep prob-
lems in children with neuromuscular disorders. Five of them
focused on respiratory problems during sleep.70e72,74,75 Presenting
a detailed analysis on sleep behaviour, the remaining 2 studies gave
an insight into the symptoms of insomnia and hypersomnia.69,73
Weakness of the respiratory muscles (thoracic wall, diaphragm)
seems to cause the reported sleep disturbances. Subsequently, this
weakness will lead to restricted respiratory capacity, impaired
respiratory control and inability to cough up their secretions.72
Since most disturbances of vegetative control manifest during
sleep, they are subsumed under the term sleep-related breathing
disorders (SBD).72 All studies reported on the presence of one of
the various SBD (obstructive sleep apnoea, central sleep apnoea,
hypopnoea, alveolar hypoventilation). Studies with a broader view
on sleep disturbance showed that children suffering neuromus-
cular disorders additionally experienced difculties initiating or
maintaining sleep, and exhibited a change in total duration of sleep,
and sleep architecture (diminished and impaired REM sleep).69,72
Cerebral palsy. Three studies provided an in-depth analysis of the
symptoms of impaired sleep in children suffering cerebral palsy.
Most frequently, there were difculties in initiating or maintaining
sleep, problems with changing from the sleep to wake state, or
SBD.16,76,77 The impaired ability of the patients to re-position him/
herself is thought to be the main factor provoking the sleep
disturbances, possibly in combination with sensory, mental,
communication, perception, behaviour impairment or epilepsy
across two studies.16,86 Newman et al. showed that children with
cerebral palsy and concomitant visual impairment or epilepsy are
more prone to sleep disturbances than their counterparts not
suffering those additional complications.16
Other cerebral disorders/injuries. It is reported in three studies that
after mild or severe traumatic brain injury,89 some types of sleep
disturbance may persist for years, in the form of difculty in initi-
ating or maintaining sleep, or excessive daytime sleepi-
ness.80,81,83,90 The psychological effect of the trauma may have
 A.-L. Tietze et al. / Sleep Medicine Reviews 16 (2012) 117e127 121

Table 1
Characteristics of the 61 studies undergoing in-depth analysis.

Authors Year of publication Country N Sample Mean age (years) Instrument Ref.
Mixed group (n 10 articles)
Piazza et al. 2008 USA 51 10.2 O 33
Cotton & Richdale 2006 Australia 16 9 Q 30
Coppola et al. 2004 Italia 27 10.5 Q 35
Bartlett et al. 1985 UK 214 n.a. Q 2
Didden et al. 2002 The Netherlands 286 8.3 Q 31
Keenan et al. 2007 UK 58 6 Q 32
MacCrosain & Byrne 2009 UK 152 7.6 Q 13
Quine 1991 UK 200 n.a. Q, I 10
Richdale et al. 2000 Australia 52 7.7 Q 34
Robinson & Richdale 2004 Australia 239 10.6 Q 19

Specied group (n 51 articles)

Syndrome (n 26 articles)
de Leersnyder et al. 2001 France 20 9.5 A 49
McArthur & Budden 1998 USA 9 10.1 A 38
McDougall et al. 2005 UK 9 12.3 I 39
Piazza et al. 1990 USA 20 9 O 37
de Miguel-Diez et al. 2003 Spain 108 7.9 PSG 45
Festen et al. 2006 The Netherlands 53 5.4 PSG 59
Miano et al. 2005 Italia 10 5.8 PSG 51
Glaze et al. 1987 USA 11 n.a. PSG 40
Schlueter et al. 1996 Germany 8 6.3 PSG 41
Williams et al. 2007 USA 37 9 PSG 57
Arens et al. 1998 USA 28 4.7 PSG, I 36
Carter et al. 2009 UK 58 8.6 Q 43
Conant et al. 2009 USA 290 n.a. Q 44
Dykens and Smith 1998 USA 35 9 Q 46
Goldman et al. 2009 USA 23 24 Q 47
Hall et al. 2008 USA 54 13.9 Q 18
Leavanon &Tarasiuk 1999 Israel 23 4.8 Q, PSG 48
Maas et al. 2009 The Netherlands 30 1.7 Q 50
Richdale et al. 1999 Australia 29 14.4 Q 54
Smith et al. 1998 USA 39 10.5 Q 55
Walz et al. 2005 USA 339 10.9 Q 58
Bruni et al. 2004 Italia 49 10.1 Q, A 42
Stores & Stores 2004 UK 46 2.8 Q, A 56
Odonoghue et al. 2005 Australia 13 n.a. Q, PSG 52
Potocki et al. 2000 USA 28 9.4 Q, PSG 60
Potocki et al. 2003 USA 58 9 Q, PSG 53

Neurodegenerative or metabolic disorder (n 8 articles)

Heikkil et al. 1995 Finland 14 15.6 A 61
Santavuori et al. 1993 The Netherlands 42 10.7 n.a. 68
Colville et al. 1996 UK 80 10.2 Q 62
Fraser et al. 2005 USA 141 13.5 Q 63
Lindblom et al. 2006 Finland 27 11 Q 65
Hunt & Burne 1995 UK 127 7 RDC 64
Maegawa et al. 2006 Brasilia 21 19.3 RDC 66
Nashed et al. 2009 Canada 11 5.2 RDC 67

Neuromuscular disorder (n 7 articles)

Suresh et al. 2005 Australia 34 10 RDC 74
Khan et al. 1996 UK 8 10 PSG 70
Kirk et al. 2000 Canada 11 n.a. PSG 71
Testa et al. 2005 Italia 14 11.7 PSG 75
Hemmingsson et al. 2009 Sweden 505 9.3 Q 69
Mellies et al. 2003 Germany 49 11.3 Q, PSG 72
Mellies et al. 2004 Germany 12 8.1 Q, PSG 73
Cerebral palsy (n 3 articles)
Kotagal et al. 1994 USA 9 3.7 PSG 76
Mobarak et al. 2000 Bangladesh 91 3.2 Q 77
Newman et al. 2006 UK 173 8.1 SD 16

Other cerebral disorder/injury (n 7 articles)

Osredkar et al. 2005 The Netherlands 191 n.a. PSG 82
Bruni et al. 1995 Italia 10 9.6 PSG, I 79
Hunt & Stores 1994 UK 40 n.a. Q 78
Pillar et al. 2003 Israel 98 13.5 Q 83
Milroy et al. 2007 UK 18 9.7 Q, A 81
Beebe et al. 2007 USA 109 n.a. Q, I 80
Florance et al. 2009 USA 32 14 RDC 84

A, actigraphy; I, interview; n.a., not available; O, observation; PSG, polysomnography; Q, questionnaire; RDC, retrospective data collection; SD, sleep diary.
122 A.-L. Tietze et al. / Sleep Medicine Reviews 16 (2012) 117e127

Table 2
Prevalence of sleep disturbances and main diagnosis.

Mixed Specied group

group
NMD NDG CP OCD/J Syndrome

AM CDC CDL D PW SM W R

% ref % ref % ref % ref % ref % ref % ref % ref % ref % ref % ref % ref % ref
57 34 71 72 78 62 44 16 90 79 70 42 30 50 55 18 40 43 100 57 100 55 36 47 - -
97 13 64 74 91 63 100 76 48 78 58 44 40 30 44 30 100 49 57 36
80 2 48 69 64 67 89 77 31 80 70 51 54 45 69 52 100 53
99 31 82 71 100 61 77 81 48 58 31 56 35 54 100 60
63 19 58 73 31 64 96 82
86 32 64 75 47 66 28 83
88 33 52 68 81 83
67 10 58 65
54 30

AM, Angelman syndrome; CDC, Cri du Chat syndrome; CDL, Cornelia de Lange syndrome; CP, cerebral palsy; D, Downs syndrome; NMD, neuromuscular disorder; NDG,
neurodegenerative or metabolic disorder; OCD/J, other cerebral disorder/injury; PW, Prader Willi syndrome; P, prevalence; ref, reference; R, Rett syndrome; SM, Smith
Magenis syndrome; W, Williams syndrome.

Table 3
Distribution of specic symptoms in sleep disturbance according to ICSD-2.

ICSD-2 main symptom Affected patient group Number of studies References

1.Insomnia All 36 2, 10, 13, 16, 19, 30, 31, 33, 34, 36e40, 42e44, 47e51, 54e56, 58, 60e62, 65,
a. Difculties initiating sleep 25 68, 69, 73, 77e79, 84
b. Difculties maintaining sleep 35
2.Sleep-related breathing disorder (SBD) CP; MS; NMD; S 19 13, 16, 34, 41, 43, 45, 50, 52, 56, 57, 59, 67, 69e76
3.Hypersomnia; daytime sleepiness CP; MS; NDG; S 14 13, 16, 30, 34, 37e39, 43, 47, 49, 54, 55, 60, 61
4.Impaired circadian rhythm MS; NDG; OCD/J; S 18 16, 37e40, 42, 44, 47e49, 55, 60e62, 73, 79, 82, 84
5.Parasomnia CP; MS; NDG; S 13 2, 16, 34, 36, 42e44, 50, 55, 58, 60, 62, 68, 84
6.Sleep-related movement disorder MS; S 7 34, 36, 42, 47, 48, 51, 65

CP, cerebral palsy; ICSD, international classication of sleep disorders; MS, mixed samples; NDG, neurodegenerative or metabolic disorders; NMD, neuromuscular disorders;
OCD/J, other cerebral disorder/injury; S, syndromes.

a more signicant impact in initiating or maintaining sleep than the
traumatic cerebral lesion itself.80,83
In children who have suffered cerebral hypoxia (hypoxic-
ischemic encephalopathy) or cerebral inammation (meningitis,
encephalitis) or in children with tuberous sclerosis, sleep distur-
bance has not been a subject of intensive investigation so
far.78,79,82,84 Four articles indicate a general tendency to show
difculties in initiating or maintaining sleep and changes in sleep
architecture as reected in electroencephalography, especially in
children who have had a hypoxic event.78,79,82,84
Assessment tools for sleep disturbance
41% of the studies used objective instruments like poly-
somnography (PSG; N 19), or actigraphy (N 6) to assess sleep
disturbances (Table 1). Of those studies, 11 additionally used
subjective instruments (questionnaire, interview) to assess sleep
quality and associated disturbances42,47,48,52,53,56,60,72,73,79,81; more
than half of the studies (57%; N 35) used questionnaires. 19
studies used internationally acknowledged sleep questionnaires
(Table 5). Another 14 studies relied on instruments newly devel-
oped or modied for the purpose of the study. However, the
psychometric quality of those instruments was not adequately
tested.2,19,30,35,42,46,48,55,63,65,69,72,73,83 Three studies used general
behaviour scales to measure sleep quality.52,77,80 Five studies relied
on retrospective data collection.64,66,67,74,84 One study used sleep
diaries,16 two studies implemented observation protocols.33,37 Five
authors used supplementary interviews with parents.10,36,39,79,80
One publication did not provide any data on the instruments
used.68 To summarize, the most frequently implemented assess-
ment method for sleep disturbance was subjective assessment
(questionnaire, interview). In questionnaire studies, 18 different
instruments were used. The psychometric quality of the imple-
mented assessment tools varied or was not adequately tested. In
addition, diagnostic criteria and cut-off values dening a sleep
disturbance differed between the questionnaires used.15,31,91

Table 4
Syndromes and associated symptoms of sleep disturbance.

Syndrome Symptom

Difculties Excessive Sleep-related Impaired Parasomnia Sleep-related Reduced total Increased level of
initiating or daytime breathing circadian movement sleep time irritation; anxiety
maintaining sleep sleepiness disorder rhythm disorders
Angelman x x x x
Cri du chat x x x x
Cornelia de Lange x
Downs x x x x x
Prader Willi x x x
Retts x x x x
Smith Magenis x x x x
Williams x x x x
 A.-L. Tietze et al. / Sleep Medicine Reviews 16 (2012) 117e127 123

Table 5
Implemented internationally consented questionnaire for sleep disturbances in disabled children in the studies.

Q Author(s) (ref.) Sample characteristics Psychometrics Samples where Q was

applied so far (ref.)
Reliability Validity
Behavioural evaluation of Schreck25 307 healthy subjects a .77 (i.c.), rt-r  .87 Construct Angelman syndrome44,58
disorders of sleep (BEDS)
Children sleep habits Owens et al.23 496 healthy subjects a .62e.78 (i.c.), rt-r .62e.79 Specicity Mixed sample13
questionnaire (CSHQ) 154 clinic patients sensitivity OCD/J81
Downs syndrome 43
Epworth sleepiness scale (ESS) Johns 107
104 healthy adult subjects a .73e.88 (i.c.), rt-r .82 Construct Williams syndrome47
150 adult clinic patients Smith Magenis syndrome53,60
Prader Willi syndrome54
Mixed sample34
Infant Sleep Questionnaire (ISQ) Morell26 289 healthy subjects rt-r .92 Criterion Cornelia de Lange syndrome18
Specicity
Sensitivity
Sleep disturbance scale (SDSC) Bruni et al.24 1157 healthy subjects a .71e.79 (i.c.), rt-r .71 Construct Cerebral palsy16
147 clinic patients
Sleep questionnaire (SQ) Simonds & Parraga108 309 healthy subjects rt-r .83e1.0 Face Mixed sample32
Downs syndrome 56
Interview based on SQ Hunt & Stores78 40 clinic patients n.a. Criterion OCD/J78,79
Modied SQ Wiggs & Stores91 209 patients with learning n.a. n.a. Mixed sample31
disabilities Cri du chat syndrome50
The Sleep Index Quine10 200 patients with disabilities a .77 (i.c.) Construct Mixed sample10

i.c., internal consistency; n.a., not available; OCD/J, other cerebral disorder/injury; Q, questionnaire; ref., reference; r t-r, test-retest validity; a, Cronbachs alpha109.

Discussion presumed to be due to differences in the degree of brain damage or

Although scientic interest in sleep disturbance in disabled
children is increasing - 60% of the studies origin from 2003 or later-,
this paper is one of the rst structured reviews on sleep disturbance
in children with multiple disabilities.
According to medical practice, in a rst step, we tried catego-
rizing children with multiple disabilities in aetiological groups for
better understanding underlying processes. Classication was not
explicit. This is reected in relatively low to moderate values of
inter-rater-agreement (k .59) regarding study allocation
based on underlying main diagnosis. Results reect the challenge
in identifying aetiology in complex disorders with multiple
disabilities.
Despite the large number of studies on sleep disturbance in
children with multiple disabilities, the cause of mental retardation
or developmental delay in many children remain unclear: an
aetiological diagnosis is identied in less than 50% of affected
patients.21 Accordingly, most studies present mixed samples of
children with multiple disabilities and do not differentiate between
different aetiologies.13,19,31,34 Studies in specic sub-populations
are scarce and mostly based on a small sample size (median of 34
children, see Table 1).
We had intended to presenting disease-specic results as
information on prevalence, type and severity of sleep disturbances
with respect to the main diagnosis would be of great benet for
clinical practice. This was an ambitious aim. Due to high rates of co-
morbidity, we could not eliminate possible confounding effects of
different aetiological factors in our results.
Outcome ndings
Prevalence
In all the studies, there was a high prevalence of sleep distur-
bance. More than two thirds of children with severe multiple
disabilities suffer from severe sleep disturbance, a number which is
substantially higher than in healthy children (3e40%) or children
with isolated mental impairment or primary psychiatric disorders
(30e54%).19,92-94
The observed differences in the prevalence of sleep disturbance
between the studies investigating comparable patient groups are
differences in the assessment tools used. Generally, the severity of
the sleep disturbance correlates with the degree of brain damage
caused by the main diagnosis. The differences in prevalence of sleep
disturbance between patient groups with different primary diag-
noses such as cerebral palsy, syndromes or neuromuscular disor-
ders, etc., were minimal. In children suffering severe generalized
cerebral degeneration (i.e., severe neurodegenerative disorder or
hypoxic-ischemic encephalopathy), the prevalence of sleep
disturbance of 90e100% far exceeded the average prevalence of
other patient groups with localized central or peripheral nervous
system involvement.49,53,55,82
Symptoms
More than half the studies reported patients who simulta-
neously had more than three sleep disturbances. Compared to
healthy children or patients with a primary psychiatric diagnosis,
in our patient group, the symptoms are much more
pronounced.13,95 Children with severe and multiple disabilities
most frequently suffer difculties initiating or maintaining sleep.
73% of the studies reported a high prevalence of insomnia, inde-
pendent of patient group. Difculties initiating or maintaining
sleep are not uncommon in healthy children during their rst
years of life.4,96 These difculties are not perceived as being
pathological. In contrast, children with multiple disabilities suffer
from profound and long lasting insomnia, not comparable with
normal stages in development. It is still unclear if this profound
insomnia in children with multiple disabilities is primarily caused
by cerebral degeneration, impairment of cerebral maturation,97,98
or increased psychosocial burden on those patients and their
families.3
Sleep-related respiratory problems were specically investi-
gated in children with neuromuscular disorders, and were reported
in all 6 studies.69e75 The most frequent problems were obstructive
apnoea due to muscular weakness, leading to repeated episodes of
hypoxia with a severe negative impact on the quality of sleep, and
quality of life of the affected patients.71e73
Since in other patient groups PSG was rarely performed, it is
debatable if disordered breathing during sleep is specic for
patients with neuromuscular disease.99 The few papers on PSG in
children with different syndromes (PradereWilli syndrome, Down
124 A.-L. Tietze et al. / Sleep Medicine Reviews 16 (2012) 117e127
syndrome, Cri du Chat syndrome) also detected sleep-related
problems.41,48,50,51,57 Obstructive apnoea is seen more frequently
than central apnoea.48,51 To date, there are few PSG studies on
children with neurodegenerative or metabolic disease.67 As a rule,
the ability of those patients to communicate is severely affected,
making it difcult to reliably estimate the impact of repeated
episodes of hypoventilation on their well-being. This is further
complicated by the frequent presence of concomitant sleep
problems.
Disturbances of the sleep-wake-cycle were predominantly seen
in children with severe and global cerebral damage and may result
in a total phase inversion of the cycle.60,62,82 These disturbances
should be differentiated from sleep cycle instability (delayed sleep
phase or onset) seen in children with mild sensory disabilities6 and
to a lesser extent in healthy children.4,96
Prevalence and symptoms of sleep disturbance with reference to the
underlying pathology of diseases
The factors responsible for the high morbidity of the patients are
still to be determined. We found no differences in prevalence of
sleep disturbances related to the underlying pathology of diseases.
Further, there were no sleep-related problems denitively and
exclusively linked to specic diagnoses such as syndromes,
neuromuscular or neurodegenerative disorders, etc. It seems more
likely that prevalence and degree of sleep disturbance are related to
the severity of brain impairment. Global cerebral impairment
presents a higher risk for the development of a severely disturbed
sleep-wake-cycle. Impairment of centres that control vigilance
within the brain stem (formatio reticularis) and mesencephalon
(hypothalamus) may cause dysregulation of endogenous or exog-
enous timing circuits. Other focal or milder global cerebral
impairments are more frequently related to difculties in initiating
or maintaining sleep, similar to what is seen in healthy children.
There is no clear correlation between sleep-related respiratory
problems and neuromuscular disease, though further PSG studies
may help clarify this.
It may be hypothesized that the extent of the cerebral distur-
bance (global vs. focal) is far more important than the underlying
main diagnosis3,20,34 in determining sleep disturbance. Further-
more, secondary factors such as pain, restlessness, epilepsy or
spasticity and psychosocial factors may cause sleep disturbance in
children with multiple disabilities.12,14-17,19,69 The inuence of these
factors needs to be explored in future studies.
Assessment
The main problem with the assessment of sleep disturbance in
children with severe and multiple disabilities is the lack of an
adequate diagnostic tool that is universally applicable on patients
with different main diagnoses, allowing for the comprehensive
assessment of symptoms and disturbances.
For the vast majority of this patient cohort, self-assessment is
not possible, and symptoms have to be interpreted by parents or
caregivers. The limited and undifferentiated behavioural repertoire
of most of those children makes the task even more difcult and
results in over-interpreting or under-reporting of symptoms. Thus,
in those patients, the reported frequency of sleep disturbance is
heavily dependent on the assessment instrument used and the
parents perception of and tolerance for the observed
symptoms.13,100
Nineteen articles used PSG for assessment of sleep disturbance.
PSG was the only way to reliably detect SBD. Objective measures
like PSG are expensive and difcult to obtain in children with
multiple disabilities, and still leave general diagnostic uncertainty.
Accordingly, PSG ndings sometimes do not correlate with clinical
sleep problems as reported by patients or parents.101,101 In contrast
to normal children, children with multiple disabilities cannot
express if changes in sleeping pattern affect their subjective mood
and quality of life. In clinical practice, the discrimination between
the characteristics and quality of distinct sleep disorders is partic-
ularly difcult for the observer.101 Although PSG is the gold stan-
dard and a valid tool in detecting sleep architecture abnormalities,
the subjective pathology should take priority over objective diag-
nostic ndings.
Most of the analyzed studies (57%) relied on questionnaires for
the assessment of sleep disturbance, and a variety of them were
used (18 different questionnaires in 35 studies). Many of the
questionnaires did not full standard quality criteria.2,19,34 Few
studies delivered data on sensitivity, specicity, or positive and
negative predictive values (see Table 5). Some of the questionnaires
were validated in healthy subjects only.31,91 Some of the studies
only looked for selected symptoms common in sleep medicine (e.g.,
daytime somnolence),48,102 others used non-specic behaviour
scales.80 Diagnostic criteria and cut-off values for dening a sleep
disturbance differed between the questionnaires used.15,31,91 There
is no dened standard for questionnaires used in assessing quality
of sleep and sleep disorders in children with multiple disabilities.103
There is urgent need to investigate the validity, reliability, and
utility of questionnaires in use, or to develop new instruments, in
order to improve the quality of assessment of sleep disturbance in
this patient group.96
Limitations
Results of our review should be considered in the context of the
following limitations. One should be cautious with the interpre-
tation of prevalence data, since there was no uniform denition of
what was considered a sleep disturbance in articles reviewed.
Sleep disturbance was dened based on the implemented
assessment tool, which varied across articles. Two third of the
studies indicated that they based their diagnoses of sleep distur-
bance on the international classication criteria ICSD,104,105 or they
relied on internationally acknowledged and validated sleep ques-
tionnaires. In addition, we did no qualitative analysis of the
studies,106 thus any outlying result in prevalence should be
regarded with caution since it may have resulted from methodo-
logical aws of the specic study or individual peculiarities of the
investigated sample.
Conclusions
Our results reect that sleep disorders in children with multiple
disabilities are a signicant clinical problem irrespective of the
underlying diagnosis. There are multiple pathogenic factors with
respect to sleep disturbance: the site and extent of any cerebral
damage, symptoms related to the patients main diagnosis (mental
retardation, spasticity, paresis, epilepsy) and secondary factors
(pain). Further psychosocial factors (parental insecurity, distress
and behaviour) and environmental factors (individual patients
circadian rhythm) playing a decisive part.3,17,22,88 Therefore, it is
important to meticulously investigate all confounding factors in
order to isolate the most signicant ones, facilitating the develop-
ment of the most appropriate approach to treatment. Most of the
studies analyzed in this paper did not explore those co-variates.
This was mainly due to the lack of suitable and validated
questionnaires.
The complexity of sleep disturbance as depicted in the present
review is essential in the design and development of standardized
assessment tools. Given that sleep disturbance poses a problem for
a variety of children with multiple disabilities, we suggest that
 A.-L. Tietze et al. / Sleep Medicine Reviews 16 (2012) 117e127
assessment tools should be structured to be more symptom-
oriented (i.e., specically designed for symptoms of sleep distur-
bances) rather than disease-specic. Ideally, the assessment tools
should be feasible for use in all patient groups and validated
within a large heterogeneous sample of children with multiple
disabilities.
We suggest the following standards for assessment tools of
sleep disturbances in children with multiple disabilities:
 The construct and aim of the test must be clearly stated.
 Items should be generated by experts and include suggestions
from parents.
 The broad domains of sleep behaviour that are to be assessed
should be clearly specied and based on the patterns dened in
ICSD.
 The proposed domains of the scale must necessarily be rele-
vant and exhaustive with regard to the target group.
 The domains selected should be mutually exclusive, to prevent
ambiguity in scoring, administration and interpretation.
 Because self-assessment is rarely feasible, symptoms and
behaviour described should be written in observable terms for
parents or caregivers.
 It is important to meticulously investigate all confounding
factors for sleep disturbances (bio-psycho-social model).
Assessment of psychological factors of the child (anxiety,
restlessness or distress) and social factors (parents insecurity,
distress and behaviour) should be given particular
importance.
 The questionnaires should be validated in a sample of children
with different types and symptoms of disabilities to ensure
applicability independent of underlying disease.
Practice points
More than two-thirds of children with multiple disabilities
suffer from severe and sustained sleep disturbance.
1) The prevalence and type of sleep disturbance depends
largely on the extent and severity of cerebral impair-
ment, while the specific cause of damage (i.e., the
primary diagnosis) has a smaller impact.
2) Difficulties in initiating or maintaining sleep are most
common in children with cerebral damage. An impaired
sleep-wake-cycle is predominant in children with global
and severe cerebral damage or with mesencephalon or
brain stem damage.
3) To understand, differentiate and determine treatments
for sleep problems, special attention must paid to
physical, psychological and social influences on the
childs sleep.
4) Sleep disturbance in children with multiple disabilities
poses a significant social and medical problem with
severe impact on various areas of life (i.e., mental
function, mood, behaviour, physical development,
child and familys quality of life).
5) The standardized evaluation of sleep disturbance by
a sensitive and validated questionnaire is important for
clinical management of affected patients as well as for
research studies. Through the implementation of such
a tool, observer bias may be reduced, the severity of the
symptom may be adequately assessed and observed
over time in an individual, and comparisons between
different individuals and populations is then feasible.
125
Research agenda
Future research on the clinical implications of sleep disor-
ders in children and adolescents with multiple disabilities
should focus on the following:
1) While it is known that SBD is frequent in children with
neuromuscular disorders, it has not been investigated
in children with neurodegenerative disorders. Further
PSG studies are warranted in this cohort of children.
2) Future reports should represent results according to the
different underlying conditions following ICSD. The
information on the underlying sleep disorder would
then be informative in formulating treatment strategies.
3) Detection and classification of sleep disorders should
be based on validated questionnaires, which should
include a detailed sleep history, and be compared with
results from objective tools.
4) The comprehensive assessment of patient factors on
the basis of bio-psycho-social model (developmental,
medical, psychological and family factors) is crucial in
isolating the most important factors and in developing
an effective treatment approach.
5) We need to define correlations between specific diag-
noses and qualified, sophisticated diagnostic tools in
order to select, or develop, optimal therapy. To this end,
the development of robust questionnaires for the
assessment of sleep disturbance is of utmost
importance.
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