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Review Article
Review of the Possible Relationship and Hypothetical Links Between Attention
Deficit Hyperactivity Disorder (ADHD) and the Simple Sleep Related Movement
Disorders, Parasomnias, Hypersomnias, and Circadian Rhythm Disorders
Arthur S. Walters, M.D.1; Rosalia Silvestri, M.D.2; Marco Zucconi, M.D.3; Ranju Chandrashekariah, M.D.1; Eric Konofal, M.D., Ph.D.4
1
New Jersey Neuroscience Institute at JFK Medical Center, Seton Hall University School of Graduate Medical Education, Edison, NJ; 2Sleep
Medicine Center, Dept of Neurosciences, Psychiatric and Anaesthesiological Sciences, Messina, Sicily, Italy; 3Sleep Disorders Center, Department
of Neurosciences, H San Raffaele Hospital, Milan, Italy; 4Pierre and Marie Curie University, Paris, France
Recent evidence has been accumulating that the sleep of individuals
with attention deficit hyperactivity disorder (ADHD) is not only disrupted in a nonspecific way but that ADHD has an increased association
with simple sleep related movement disorders such as restless legs
syndrome/periodic limb movements in sleep (RLS/PLMS), rhythmic
movement disorder (body rocking and head banging), and parasomnias, such as disorders of partial arousal (sleep walking, sleep terrors, and confusional arousals). In addition increased associations
have been reported between ADHD and hypersomnias such as narcolepsy and sleep apnea as well as circadian rhythm disorders, such
as delayed sleep phase syndrome. These relationships are reviewed
and the implications for such associations are explored. Patients with
sleep disorders should be queried about the symptoms of ADHD and
vice versa.
Keywords: Restless legs syndrome, periodic limb movements in
sleep, rhythmic movement disorder, sleep walking, confusional arousals, night terrors, narcolepsy, sleep apnea, delayed sleep phase syndrome
Citation: Walters AS; Silvestri R; Zucconi M; Chandrashekariah R;
Konofal E. Review of the Possible Relationship and Hypothetical Links
Between Attention Deficit Hyperactivity Disorder (ADHD) and the Simple Sleep Related Movement Disorders, Parasomnias, Hypersomnias,
and Circadian Rhythm Disorders. J Clin Sleep Med 2008;4(6):591600.
T
his review arises out of a clinical workshop run by 4 of
the authors of this article (ASW, RS, MZ, EK) on June 21,
2006, at the Associated Professional Sleep Societies meetings
in Salt Lake City, Utah. The workshop entitled “Relationship of
Attention Deficit Hyperactivity Disorder (ADHD) to Sleep Disorders” had the stated purpose of understanding “the relationship of Attention Deficit Hyperactivity Disorder to: Restless
Legs Syndrome and Periodic Limb Movements in Sleep; Sleep
Apnea; Narcolepsy; Disorders of Partial Arousal; Rhythmic
Movement Disorder; and Sleep-Related Epilepsy.” The workshop concluded that symptoms of inattention and hyperactivity
or ADHD occur commonly in a variety of specific sleep disorders and, in turn, that patients with ADHD commonly have a
number of specific sleep disorders.
The seminar was well received, and because of the frequency
of the association between ADHD and specific sleep disorders,
we feel that it is time for a written review of this material. The
potential therapeutic implications of such associations are obvious. Unlike so many articles and reviews that focus on the sleep
disruption in pure ADHD, this review summarizes the growing
literature showing the relationship between ADHD or ADHD
symptoms and very specific sleep disorders. To the topics discussed at our original seminar, we add evidence showing a relationship between ADHD and delayed sleep phase syndrome.
Sleep related epilepsy is not covered in this review. To our
knowledge, this is the first review summarizing the relationship between ADHD and all 6 of the disorders listed. Table 1
summarizes the results of this survey and will be available as
an online supplement.
Narcolepsy
Narcolepsy is characterized by excessive daytime drowsiness with or without sudden loss of body tone under conditions
of strong emotion (cataplexy).1 Hypnagogic hallucinations and
sleep paralysis are frequently associated features.
ADHD Symptoms in Narcolepsy
Inattention in Narcolepsy
The prevalence of ADHD symptoms in patients with narcolepsy approaches 18.9% in one study.1 It is obvious that patients
with narcolepsy can have decreased attention because they are
drowsy during the day. This is captured in abnormalities of
tests of arousal /alertness. Arousals can be divided into phasic
(tasks that require immediate attention) and tonic (tasks that re-
Submitted for publication September, 2007
Accepted for publication July, 2008
Address correspondence to: Arthur S. Walters, M.D., Department of Neurology, Vanderbilt University Medical Center, MCN-A-0118, 1161 21st Ave
South, Nashville, TN, 37232-2551; Tel: (615) 322-0283, Fax: (615) 9360223, E-mail: [email protected]
Journal of Clinical Sleep Medicine, Vol. 4, No. 6, 2008
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AS Walters, R Silvestri, M Zucconi et al
quire sustained attention).2 Patients with narcolepsy do poorly
on tests of arousal as can be shown by poor performance on
the Critical Flicker Fusion test,3 which measures the frequency
at which a rapidly changing on-off light signal is perceived as
stationary by a subject. In an overall sense, the Critical Flicker
Fusion test is thought to be a measure of tonic arousal.3
Patients with narcolepsy also do poorly on tests of selective
attention. Selective attention is divided into focused attention
(continuous focus on a single task), flexible attention (one must
switch from one task to another) and divided attention (one must
do 2 tasks at once).2 Examples would be poor performance on
Strub and Black’s List of Letters, a digit symbol substitution
test, and a visual tracking test, all of which measure focused
attention.3,4 Deficits in flexible attention have also been shown
in tests in which patients are asked to respond to a number or
a letter which are presented simultaneously but with a shifting
paradigm; sometimes the patient has to respond to the number
and sometimes the letter.2 Divided attention in narcolepsy is abnormal, as shown by difficulties in performing separate visual
and auditory tasks simultaneously.2
Patients with narcolepsy do worse on simple tests that take
more time and are boring and better on tests that require less
time and are complex and interesting.2,5 For example, patients
do well on the Paced Auditory Serial Addition Test (PASAT)
which is complex but short and measures divided attention.4
However, in many instances the length of the task and the complexity are confounded, e.g., the more complex tasks may also
be the ones that are shorter. In addition, complex tasks are more
demanding and interesting, and therefore could be more alerting. Thus, the level of attention may be confounded with the
level of alertness. Others have pointed out that narcoleptics may
have cognitive difficulties as well, particularly in the area of
executive function, which is the ability to organize, plan, prioritize, and execute various activities in an appropriate sequence.
Deficits in executive function may be a result of the drowsiness
narcoleptics experience. Because of drowsiness, narcoleptics
have to spend so much of their mental energy focusing on even
simple tasks that they do not have mental residual to focus on
the greater complexities of task integration.6 Hood and Bruck
examined narcoleptics in both high and low states of arousal
and found that complex cognitive tasks are the most sensitive
to arousal fluctuation.7
Abnormalities in narcolepsy have also been found in the
Sustained Attention to Response Task (SART) and in the automobile driving simulation task “Steer Clear.8,9 Both of these
probe multiple aspects of the attentional matrix simultaneously.
Neurophysiological tests such as the measurement of the P300
and mismatch negativity have also been used to explore the attentional matrix in narcolepsy.10
Nauman and Daum have summarized the research on cognition and narcolepsy nicely up to 2003. In summary, narcoleptics have trouble with memory (additional examples include response latency, word recall, estimation of frequency), attention
(additional examples include Wilkinson auditory vigilance task,
10-minute choice reaction time test) and executive function (an
additional example is Sternberg’s STM Scanning task). However, it is important to remember that these kinds of deficits are
not found in all studies. 4
Journal of Clinical Sleep Medicine, Vol. 4, No. 6, 2008
Hyperactivity in Narcolepsy
One of the glaring deficits in this area of research is that there
has been no attempt to see if narcoleptic patients are also hyperactive. It is theoretically possible that narcoleptics move more
in order to stay alert, but this has not been formally tested.
Narcolepsy Symptoms in ADHD
More than a third of adults with ADHD are drowsy, as determined by a score >12 on the Epworth Sleepiness Scale according to one study.1 In ADHD patients, inattention scores
correlated with the excessive daytime sleepiness scores. Of
course, daytime drowsiness may be caused by disorders (such
as sleep apnea) other than narcolepsy. In another study, 34
children with ADHD (average age 12.4 y) were objectively
more drowsy than controls on a modified multiple sleep latency test, in which naps were not terminated at 20 minutes
(21.9 min vs 27.9 min), p < 0.05, but half of the ADHD group
had symptoms of obstructive sleep apnea as opposed to only
22% of the control group. In addition, the authors did not state
whether or not they looked for 2 sleep onset REM periods,
which is the hallmark of narcolepsy on MSLT.11 In another
study by Lecendreux et al on an unselected population of 30
boys with ADHD, aged 5-10 years, results were similar with
shorter sleep latencies for ADHD patients than controls in
naps 1, 2, and 3. Number and duration of sleep onsets measured by the MSLT correlated significantly with hyperactivityimpulsivity and inattentive-passivity indices, as measured by
the Conners Parent and Teacher rating scales. None of these
differences could be attributed to any differences in nocturnal
sleep. Again, the authors did not state whether they looked for
2 sleep onset REM periods on the MSLT.12 In a later study by
the same group, in which corrections were made for the presence of anxiety and depression in 45 obese children aged 1016 years (not selected for ADHD), drowsiness still remained
associated with ADHD symptoms in those children from the
group that had ADHD symptoms.13 To our knowledge, there is
no study that systematically evaluates individuals with ADHD
for the presence of either the MSLT findings of narcolepsy
or secondary features of narcolepsy (sleep paralysis, hypnagogic/hypnopompic hallucinations, or cataplexy).
Summary: To summarize, symptoms of inattention are common in narcolepsy, but symptoms of hyperactivity in narcolepsy need to be further explored. Drowsiness is common in
ADHD, but the prevalence of narcolepsy in ADHD remains to
be determined.
Rhythmic Movement Disorder
Rhythmic Movement Disorder (RMD) primarily occurs in
young children and is characterized by head banging or body
rocking prior to sleep onset and sometimes during sleep itself.
Most children outgrow the disorder. It is not truly considered a
disorder unless sleep-related injury is present (which is uncommon), or daytime consequences related to reduced sleep quality
are present (ICSD-2). The disorder often disappears as children
age.14
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Review of the Relationship between ADHD and Specific Sleep Disorders
ADHD Symptoms in Rhythmic Movement Disorder
Taken from the opposite perspective, 150 children and adolescents with various psychiatric problems were compared to a normal control group of 309 subjects from the general population.
Fourteen of the psychiatric patients had ADD, and 6 of these 14
had head banging, compared to none in the control group.17 This
result will obviously have to be verified in a larger study.
Summary: ADHD seems to be more common in RMD and,
in turn, RMD seems to be more common in ADHD. The sample
sizes tested are small, and results need to be confirmed in larger
series. Whether sleep disruption from RMD leads to symptoms
of ADHD, or whether a program for increased motor activity
has a common diathesis in both RMD and ADHD bears further
investigation.
al of chronotherapy in the morning along with a behavioral
modification program resulted in significant improvement in
ADD symptomatology.18 Gruber et al in 2000 pointed out that
28 children with ADHD who were monitored with actigraphs
and sleep diaries for 5 consecutive nights often had evidence
of sleep onset insomnia.20 Van der Heijden et al in 2005 specifically characterized this sleep onset insomnia as a component
of delayed sleep phase syndrome (DSPS).21 They compared 87
children with ADHD and sleep onset insomnia to 33 children
with ADHD and no sleep onset insomnia. Salivary melatonin is
a marker of circadian phase and is secreted only in the dark. The
onset of secretion of melatonin under conditions of reduced illumination can be measured as the DLMO (dim light melatonin
onset).The DLMO in the ADHD insomnia patients occurred at
a much later time in the evening than in the ADHD patients
without insomnia. This strongly implies that the sleep onset
insomnia in ADHD is due to delayed sleep phase syndrome.
Wake up time was also later in the ADHD insomnia group,
again suggesting delayed sleep phase syndrome. The quality
of sleep was comparable in both groups, thus suggesting that
sleep quality was not a confounding issue. In 2006 Rybak et al
performed an open trial of bright light therapy in the morning in
29 adults with ADHD. There was a significant phase advance in
bedtime preference with comparable improvements in ADHD
symptomatology.22
Summary: ADHD seems to be characterized, in some cases,
by a sleep onset insomnia characteristic of delayed sleep phase
syndrome. On the other hand, the reverse relationship does
not seem to hold, as a preliminary study suggests that ADHD
symptoms are not common in delayed sleep phase syndrome. It
may be that hyperactivity at night in ADHD causes a delayed
sleep onset characteristic of Delayed Sleep Phase Syndrome,
but that the sleep disruption from a delayed sleep onset is not
enough to cause daytime inattention and hyperactivity characteristic of ADHD.
Circadian Rhythm Disorders—Delayed Sleep Phase
Syndrome
Restless Legs Syndrome and Periodic Limb
Movements in Sleep (RLS/PLMS)
Delayed sleep phase syndrome occurs primarily in adolescence and is characterized by sleep onset insomnia if the individual tries to go to sleep early. However, if the individual
is allowed to go to bed later and sleep later, the insomnia and
subsequent daytime drowsiness disappear. In delayed sleep
phase syndrome, the individuals with a propensity to sleep at
a later time than normal is thought to be mediated through the
biological clock located in the suprachiasmatic nucleus of the
hypothalamus.18
Restless legs syndrome (RLS) is a common sensorimotor
disorder characterized by an irresistible urge to move the legs,
which is often accompanied by uncomfortable sensations in the
legs or, less frequently, other body parts. These sensations are
worse at rest, relieved by movement, and worse in the evening
or night and at rest. In RLS, patients frequently experience insomnia from the leg discomfort and the need to move around.
The diagnosis of RLS is based on the revised RLS criteria developed by the International Restless Legs Syndrome Study
Group (IRLSSG).23 Although RLS is traditionally considered
a disorder of middle to older age, several case series show that
it may occur in childhood.24 In addition, one large survey of
10,523 families in Britain and the United States showed that
clinically significant RLS occurs in 0.5% of children and 1%
of adolescents.25 However, children may report RLS symptoms
differently than adults, in part because of their limited ability to
describe RLS sensations. Moreover, the clinical presentation of
RLS may differ in children. Considering these particularities,
the IRLSSG has proposed a set of criteria specific for childhood.23
Dyken et al were the first to note the association between
ADHD and RMD. They reported that 3 of 7 children, aged 1-12
years, with video-polysomnographically documented RMD
had attention deficit disorder (ADD) by past medical history.15 No attempt was made to confirm the ADD diagnosis, and
the observation went without further comment. Stepanova et
al confirmed these results: ADHD was present in 6 of 10 children with RMD who were formally assessed for the presence of
ADHD symptoms.16 The authors found the inattentive subtype
in 4 of the 6 children with ADHD and the combined inattentive
and hyperactive type in 2 of the 6 children with ADHD. The
authors suggest that immaturity of premotor and striatal circuits
may be involved in both RMD and ADHD, or that RMD may
be yet another sleep disorder potentially causing symptoms of
ADHD. The subjects in this study were beyond the age range at
which RMD usually disappears (average age in this study 14.7
years) and one of the subjects was an adult, aged 24 years.16
Rhythmic Movement Disorder in ADHD
ADHD Symptoms in Delayed Sleep Phase Syndrome
A preliminary study did not find ADHD to be present in 5
adults with delayed sleep phase syndrome.19 This relationship
remains to be further explored.
Delayed Sleep Phase Syndrome in ADHD
In 1991 Dahl et al described a 10-year-old girl with ADD
and a 5-year history of delayed sleep phase insomnia. A triJournal of Clinical Sleep Medicine, Vol. 4, No. 6, 2008
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AS Walters, R Silvestri, M Zucconi et al
Patients with RLS also frequently have a related sleep disorder called periodic limb movements in sleep (PLMS). PLMS
are defined as movements that last 0.5–10 seconds and recur
every 5 to 90 seconds in a series of ≥ 4.26 They more commonly
affect the legs, although the arms may be involved as well. Typical movements consist of simultaneous flexions of the hips,
knees, and ankles. Eighty percent of adult patients with RLS
have PLMS.23 PLMS have been reported in children with RLS
although their prevalence in children has not been adequately
studied.23 In RLS, the role of PLMS in the production of insomnia or daytime symptoms of fatigue is controversial. However, periodic leg movements sometimes occur in wakefulness
(PLMW) in RLS and may contribute to the insomnia.23
In last decade, there has been growing research in sleep disruption associated with ADHD.6 It has been correctly pointed
out that sleep disturbances may (1) mimic ADHD symptoms in
the evening or (2) be associated with ADHD symptoms.27,28 In
both cases, the appropriate treatment of sleep disturbances may
significantly improve diurnal ADHD symptoms.
Given the relationship between RLS and sleep fragmentation, some clinicians started to look for a potential association
between ADHD and RLS symptoms. Since then, interest in the
link between ADHD and RLS has progressively grown. In a
survey of the literature completed in 2005, Cortese et al29 reviewed available evidence on the relationship between RLS
and ADHD.29-35 In addition, new studies have emerged since
then.36-38
In light of these considerations, the aims of this section are
(1) to critically review evidence on the relationship between
ADHD and RLS; (2) to examine the potential mechanisms underlying this relationship; and (3) to present some future directions for the research in this area.
which all adult RLS patients were examined and interviewed
personally, administered all 18 questions of the DSM-IV criteria for ADHD, and given a full battery of psychometric studies.35 Moreover, as acknowledged by the Gamaldo et al, public
awareness of ADHD has changed considerably in the last 40
years. As the mean age of their subjects was 47, the ADHD
diagnosis may have been largely unrecognized in most of them
during their childhood.38 In addition, as opposed to the study by
Gamaldo et al, the study by Wagner et al took note of symptoms
of ADHD that began in adulthood as well as in childhood.35,38
Of the 20 RLS patients with a Brown ADHD adult rating scale
>40, one-fourth had onset of ADHD symptoms in adulthood.35
It may therefore be that those ADHD symptoms that began in
adulthood are truly secondary to RLS. Further epidemiological
studies using more rigorous criteria are welcome to better assess the relationship between ADHD and RLS.
RLS in ADHD
After reviewing the literature, Cortese et al concluded that up
to 44% of children with ADHD have RLS or RLS symptoms.29
One study in adults showed that 20 % of adults with ADHD
have RLS as opposed to only 7.2% of controls (p < 0.01).37 The
average age of the patients was 43.5 years (range 19-65 years).
However, the data on ADHD in RLS and RLS in ADHD
should be considered with caution given some limitations of
the reviewed studies. Firstly, with the exception of some of the
studies, e.g., that of Picchietti et al, where ADHD was very
prominent in RLS children in the U.S. population, these studies
were performed in clinical samples.25 Therefore, possible selection bias cannot be ruled out.
Second, not all studies used full standard criteria for the diagnosis of ADHD or RLS, particularly RLS in children. Therefore,
in some studies it is not clear whether the association between
ADHD and RLS symptoms is the expression of a real comorbidity between 2 disorders (diagnosed according to formal criteria) or, alternatively, whether RLS mimics some symptoms
of ADHD and vice versa. However, as correctly pointed out by
Wagner et al, where standard diagnostic criteria were used, it
is unlikely that the association between ADHD symptoms and
RLS is simply an artifact of overlapping hyperactivity.35 In their
study, the authors reported that RLS was associated with symptoms of inattention as well as of hyperactivity. Moreover, the
leg discomfort characteristic of RLS has not been reported in
classic idiopathic ADHD.
Restless Legs Syndrome
ADHD in RLS
In a recent study in children by Kotagal and Silber, 8 (25%)
of 32 patients with childhood RLS demonstrated inattentiveness.36 In a large community-based cross-sectional survey of
866 children, symptoms of ADHD, by objective indices, were
almost twice as likely to occur with symptoms of RLS than
would be expected by chance alone.33 There was a high hyperactivity index in 18% of children with RLS and 11% of children
without RLS. The odds ratio between a high hyperactivity index
and other parameters was 1.6 for PLMS, 1.9 for RLS, and 1.9
for growing pains. Results were similar for inattention. It has
been noted in other studies that “growing pains” may be a misdiagnosis for childhood RLS. In another study by Wagner et al,
up to 26% of adult subjects with RLS (average age 60.8 y [age
range 47.7-73.9 years]) were found to have ADHD or ADHD
symptoms, compared with 6% of patients with insomnia and
5% of normal controls (p < 0.01).35 A recent large epidemiological study by Gamaldo et al. showed no increased prevalence
of ADHD in adults with RLS.38 However, the conclusions of
this survey should be taken cautiously since the diagnosis of
ADHD was based on one item only (“Attention or hyperactivity
problems as a child”) from a retrospective telephone interview
of adults. This is in contrast to the study by Wagner et al, in
Journal of Clinical Sleep Medicine, Vol. 4, No. 6, 2008
Periodic Limb Movements in Sleep
A number of studies have examined the relationship of
ADHD to PLMS31,33,34,39-44 A recent meta-analysis summarizing
several such studies showed an intimate link between ADHD
and PLMS.45
ADHD in PLMS
Children with PLMS on polysomnography have more
ADHD. Approximately 44% of children with PLMS have been
found to have symptoms of ADHD.42 In a second polysomnographic study, the prevalence of ADHD in children with PLMS
594
Review of the Relationship between ADHD and Specific Sleep Disorders
>5/h was even higher, with 117 of 129 meeting objective criteria for ADHD.43 However, there is some degree of selection bias
in this second study, as the center also studies ADHD patients
polysomnographically in addition to patients with other sleep
disorders
lying down. According to Picchietti et al., some children who
are seriously affected with RLS cannot sit in school during the
day for extended periods because they get up and walk around
to relieve their leg discomfort.31 This hyperactivity might thus
lead to inattention through the mechanism of leg discomfort in
a subgroup of patients.
Alternatively, both RLS and ADHD might be manifestations of a common central nervous system disease. Children
with RLS and a subset of children with ADHD might share a
common dopaminergic deficit. Several lines of evidence have
shown a dopaminergic dysfunction in the midbrain, frontal, and
prefrontal regions of the brain in patients with ADHD.48 It has
also been demonstrated that dopamine deficiency is involved
in the pathophysiology of RLS.49 Iron deficiency might also
contribute to the pathophysiology underlying the association
between RLS and ADHD. The group of Konofal et al first reported significantly lower serum ferritin levels in children with
ADHD than in controls without ADHD.50 MRI, CSF, and autopsy studies have also shown that iron deficiency is involved in the
pathophysiology of idiopathic RLS.51,52 The hypothesis of iron
deficiency is compatible with the hypothesis of dopaminergic
dysfunction, since iron is a cofactor for tyrosine hydroxylase,
the rate-limiting enzyme for dopamine synthesis. Moreover,
iron deficiency has been described to alter dopamine D1 and D2
receptor density and activity in animals. Improvement of RLS/
PLMS with dopaminergic agents and iron lend support to the
idea that RLS and PLMS may be characterized by dopamine
and iron deficiency states.53-57 In addition, treatment of RLS/
PLMS with dopaminergic agents not only improves the RLS/
PLMS but also improves ADHD symptoms.53 This suggests
that RLS/PLMS and ADHD may share a common dopaminergic deficit or that the sleep disruption from RLS/PLMS may
lead to symptoms of ADHD. Moreover, we and other groups
of researchers, have seen a familial aggregation for ADHD and
a familial aggregation for RLS. One possibility to be further
explored is whether RLS and ADHD are genetically linked, explaining their more common co-occurrence.
Summary: Clinical experience suggests that RLS/PLMS
and ADHD symptoms may co-occur, in both children and in
adults. Clinical and basic research on the exciting but usually
overlooked relationship between RLS/PLMS and ADHD is still
limited.
Large cross-sectional and longitudinal studies using rigorous
standard diagnostic criteria for RLS and ADHD are necessary
to better understand the relationship between these disorders.
Research on potential mechanisms underlying the association between RLS/PLMS and ADHD are needed. In particular,
genetic studies to gain insight into potential common genetic
underpinnings are welcome. Such research should help us understand if ADHD and RLS coexist as comorbid disorders with
distinct etiopathogenesis, if they share common underlying
pathophysiological alterations, or if one of the disorders leads
to symptoms of the other one.
All this body of research should lead to a better understanding of the relationship between ADHD and RLS, allowing a
better and more specific clinical management of patients who
present with both of these disorders. We suggest that clinicians
systematically look for RLS in patients with ADHD, and, inversely, to look for ADHD symptoms in patients with RLS.
PLMS in ADHD
In two different series, between 26% and 64% of children
with ADHD had PLMS greater than 5/h of sleep.31,39 In the first,
in which 69 ADHD patients were studied, 8 (44%) of 18 children with ADHD and PLMS >5/h of sleep had both a personal
and parental history of RLS.31 In the second, 8 (32%) of 25
parents of the children with ADHD had symptoms of RLS as
opposed to none of the control parents.39 In that same study, 6
(67%) of 9 children who had both ADHD and PLMS >5/h of
sleep had a parent with RLS.39 These data suggest a possible genetic link between RLS-PLMS and ADHD. Martinez and Guilleminault showed that 7 of 11 prepubertal children with ADHD
had PLMS.40 Golan and colleagues showed that 5 (15%) of 34
ADHD patients but none of 32 controls had PLMS.41 The previously mentioned studies are largely polysomnographic and
objective, but a survey of possible PLMS in 283 school children
aged 7-14 years by Gaultney et al also found an association
between PLMS and ADHD. There was an additional association between SDB and ADHD, but the link between PLMS and
ADHD was stronger 44
Theoretical Links between RLS/PLMS and ADHD
Several Hypotheses may explain the Relationship Between RLS
and ADHD.
The first hypothesis takes into consideration the sleep disruption associated with RLS. Patients with RLS often have severe
insomnia because of leg discomfort and periodic limb movements while trying to fall asleep (PLMW). Moreover, associated PLMS may possibly, but less frequently, disrupt sleep because of associated multiple arousals. Although in adults, sleep
disruption from any cause results in excessive daytime sleepiness, such disruption in normal children can lead to symptoms
of inattention, impulsivity, and motor hyperactivity. According
to the hypoarousal theory of ADHD, children with ADHD are
actually sleepier than controls and therefore use motor hyperactivity as a strategy to stay awake and alert, in order to counteract
the tendency to fall asleep.46 Lecendreux et al. were the first to
lend possible evidence to this hypothesis with objective measures of daytime sleepiness (i.e., using the MSLT) in a sample
of children with ADHD.12 The findings of two other research
groups are in line with these results.11,47 Therefore, RLS might
lead, in some patients, to symptoms of ADHD through sleep
disruption. Thus, a circular relationship could exist between
RLS and ADHD with RLS exacerbating or leading to ADHD
through the mechanism of sleep disruption. The attendant daytime drowsiness or fatigue from sleep disruption could, in turn,
exacerbate the motor restlessness of RLS.
Another hypothesis is that diurnal manifestations of RLS
may lead to ADHD symptoms. Although RLS occurs primarily
at night, it may occur during the day when patients are sitting or
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AS Walters, R Silvestri, M Zucconi et al
Obstructive Sleep Apnea
control group exhibited an AHI > 1 in only 4% of the cases.67
The study also showed that individuals with both ADHD and
OSA have poorer attention, slower response, and higher hyperactive subscale scores on the CBCL, compared with to ADHD
children without SDB (OSA worsens ADHD symptoms?). This
is an important study, although it has some limitations, as the
high prevalence of ADHD in Taiwan (5% to 10%), the craniofacial predisposition to OSA (shorter cranial base), and the high
incidences of respiratory allergies, mean that the results cannot
be currently generalized to all patients with ADHD. The same
authors studied a group of 66 children with ADHD who also had
mild OSA (AHI > 1 < 5). These children had a compromise in
daytime symptoms (including attention span) and in subscales
for impulse control and response time that was reversed by surgical treatment of OSA (adenotonsillectomy). These results were
favorable in comparison to two other non-surgical ADHD/OSA
groups who were treated with methylphenidate or not treated at
all.68 O’Brien et al evaluated children with the Conners Parent
Rating Scale and polysomnography. Forty-four children with significant symptoms of ADHD, 27 with mild symptoms of ADHD,
and 39 with no symptoms of ADHD were analyzed. Polysomnography in these children showed an AHI >5 in 26% of those
children with mild ADHD symptoms, compared to 5% of those
with significant ADHD and 5% of controls.59 This has lead to the
suggestion that sleep disordered breathing leads to a mild mimic
of true ADHD rather than true ADHD itself.
An opposite position is that of Sangal et al who recently performed a PSG study in a group of 40 prospectively recruited 6to 14-year-old DSM-IV diagnosed ADHD children. After exclusion of those with an RDI <5, the authors found no OSA in the
ADHD group and concluded that OSA is not a common finding
or an etiological factor in ADHD.69 However, with less narrow
PSG criteria for the diagnosis of apnea, 57% of the sample had
an AHI >1, with results similar to the other studies. Also Cooper et al, in two small groups of ADHD children (n = 18, mean
age 10.5 years) and controls (n = 20, mean age 10.0 years) did
not find a difference in AHI between the two groups.70
Obstructive sleep apnea (OSA) is characterized by relaxation
of throat muscles during sleep and temporary obstruction of the
airway for ≥ 10 sec. An apnea/hypopnea index >30/h is considered severe and, over time, patients with OSA are possibly
more subject to hypertension, heart disease, and stroke.32,58-60
A number of studies have examined the relationship between
sleep disordered breathing and ADHD.45,47,58-71
ADHD in Obstructive Sleep Apnea
Li et al measured the impact of adenotonsillectomy on sleep
related adverse events and behavioral problems in children with
sleep disordered breathing.64 After surgery, all the measures
(AHI, Tests of Variable Attention (TOVA) scores, and Child
Behavior Checklist scores) improved, but with no correlation
between AHI and TOVA score.64 The indication of the existence
of SDB-related ADHD or an exacerbation of idiopathic ADHD
by SDB came from this paper, with a further recommendation
to explore ENT surgery for ADHD children with OSA.
Obstructive Sleep Apnea in ADHD
Starting from subjective measures, there are some clear indications that parents of ADHD children more frequently report sleep
related problems in their children than parents of controls.32,58-60
However, when we take in to account studies that objectively
measure sleep disorders, this conclusion is not so clear, and a
definite association between OSA and ADHD is far from ascertained. Different factors confound the results of the research
and prevent a clear conclusion in the field: the difference in the
definition of ADHD and, consequently, different patient populations enrolled in the studies; the age range and gender of children
included; different sources of recruitment of ADHD children;
and, finally, differences in the methodological approach for PSG
studies. In a recent meta-analysis of PSG studies in ADHD children, Sadeh et al found that one of the sources of variations in the
relationship between OSA and ADHD was the definition and the
measurement of apnea and hypopnea in children.45 The authors
were hopeful that some differences between ADHD and controls
would emerge with standardization of definitions for abnormal
respiratory events in children, including upper airway resistance
syndrome. On the other hand, another meta-analysis found that
children with ADHD have a mean AHI that is 1 per hour greater
than controls.27 Although this data is of statistical significance,
the implication for clinical practice is not clear.
Goodwin et al., evaluating 1494 children with an age range
from 4 to 11 years by questionnaire, found that learning problems were associated with snoring, witnessed apnea, and excessive daytime sleepiness, and were more frequent in Hispanic than
in Caucasian children.66 A more recent case-control study using
polysomnography showed more SDB in ADHD children (50%,
mean RDI 9.9 ± 6.9) than in controls (22%, mean RDI 0.8 ±
1.0).11 In a larger sample of consecutive Taiwanese children with
ADHD, observed in a specialized University Center and diagnosed according to the DSM-IV criteria, Huang and colleagues
found that nearly 57% of the ADHD children had an elevated
apnea-hypopnea index (AHI > 1), and 20% had an AHI > 5. A
Journal of Clinical Sleep Medicine, Vol. 4, No. 6, 2008
Theoretical Links Between OSA and ADHD
The possible mechanisms for the link between OSA and ADHD
are sleep fragmentation and episodic hypoxia. Sleep disruption
leads to nonrestorative sleep that, together with intermittent hypoxia or hypercarbia and the consequent disruption of cellular or
chemical homeostasis, may induce alterations in the neurochemical substrate of the prefrontal cortex. This in turn may result in
executive dysfunction with adverse daytime effects such as poor
planning, disorganization, rigid thinking, difficulty in maintaining attention and motivation, emotional lability, and overactivity/
impulsivity.61 Another point in favor of this hypothesis are the
improvements in behavior, neuropsychological functioning, and
sleepiness after treatment of SDB.59,62-65
The results to date suggest that it is generally the milder
forms of SDB rather than the more severe ones that tend to be
more common in ADHD children than in controls. This may
be due both to the more frequent occurrence of milder as opposed to more severe OSA in the pediatric community, and to
somnolence during the day in the severe cases, masking hyperactivity.71 Intermittent hypoxia and sleep fragmentation, if pres596
Review of the Relationship between ADHD and Specific Sleep Disorders
Disorders of Partial Arousal in ADHD
ent, may change the behavioral phenotype from mild SDB with
ADHD symptoms to severe SDB with somnolence.12,47,69 This
may explain the lack of correlation between objective measures
of SDB and ADHD symptoms.71 It is also the milder forms of
ADHD that tend to be more common in SDB. Thus the etiology
of ADHD may vary: There is a “primary” ADHD with no OSA
or other sleep disorders characterized by a reduced sleep fragmentation at night (hypoarousal) and increased levels of daytime sleepiness on MSLT, and a “secondary” ADHD, i.e., due
to sleep disorders (OSA, PLMS), that, when treated result in
improvement of the ADHD symptoms. As mentioned, studies
looking at the association of SDB and ADHD suggest that sleep
disordered breathing may cause a mild mimic of true ADHD
rather than true ADHD itself.59 Also, as summarized earlier, the
results of recent studies do indeed indicate that ADHD may improve with treatment of OSA.61,68,72
To our knowledge, no studies in obese children with ADHD
have considered the effect of weight reduction on the symptoms
of ADHD in parallel with the improvement of sleep disordered
breathing. Although the literature suggests that ADHD symptoms improve with the treatment of sleep apnea, no studies have
tried to find out whether treatment of ADHD affects the severity
of OSA. For example, there is no mention of a parallel treatment effect on OSA for the nonstimulants used to treat ADHD,
e.g. atomoxetine, bupropion, the α-2 adrenergic agents guanfacine and clonidine, tricyclic antidepressants, or modafinil.
Summary: It is possible that OSA can cause mild inattention
or hyperactivity, but it is still questionable whether children
with a diagnosis of moderate to severe ADHD suffer from inattention or hyperactivity as a result of OSA. SDB may contribute
to some mild ADHD-like symptoms that can be readily misperceived and may be the theoretical basis of overlap between the
2 diagnoses. This indicates the impact of a low level of SDB not
only on sleep parameters but also on cognitive tasks, and consequently on behavioral and neurocognitive functions of children
with ADHD. Therefore, the search for a respiratory disorder by
PSG and the treatment, when present, are measures to take into
account before starting long-term drug treatment for ADHD.
Longitudinal and prospective studies evaluating the treatment
effect of both the disorders may eventually clarify the relationship between OSA and ADHD.
Disorders of Partial Arousal share several common mechanisms with ADHD including familial predisposition, increased
numbers of arousals, sleep fragmentation and discontinuity, increased slow wave sleep, increased prevalence of sleep disordered breathing and an increased prevalence of rolandic foci.7275
Nonetheless, very few reports so far, in addition to that of
Silvestri et al,75 have investigated the prevalence of disorders of
partial arousal in ADHD.76,77 In one of these studies (Ishii et al.),
there was a low incidence of night terrors (NT) and sleepwalking (SW) in ADHD (2.9%) in 68 patients (mean age 9.7 y).76
In that paper, the authors explored via clinical interview a vast
range of comorbidities in ADHD from mood to conduct disorders, sleep disorders, and epilepsy. The authors found an overall
lower prevalence of comorbidities in their ADHD subjects than
those conventionally reported in North America. They attribute
this disparity to a possible bias towards milder cases, since their
children were all outpatients from a clinic without inpatient facilities. On the other hand, Gau et al. surveyed 2284 first-year
college students and found an odds ratio between sleep terrors
and inattention of 2.4 (95% CI 1.3 to 4.5) among subjects with
definite ADHD compared to non-ADHD subjects, and 1.8 (95%
CI 1.4 to 2.3) among subjects with probable ADHD compared
to non-ADHD subjects. Between sleep terrors and hyperactivity she found an odds ratio of 2.4 (95% CI 1.5 to 4.1) for subjects
with definite ADHD and 2.0 (95% CI 1.3 to 3.1) for subjects
with probable ADHD compared to non-ADHD subjects (all results at least p < 0.01). Results for sleepwalking were similar,
but the relationship was not as strong.77
Miano et al47 found indirect evidence of sleep pattern immaturity in ADHD children recorded by PSG overnight compared
to normal controls. In particular the authors report a lower cyclic alternating pattern (CAP) rate and a lower number of CAP
sequences, with longer duration of A1 subtypes in patients versus controls, supporting the hypothesis of a hypoarousal state
in these patients. Thirty-five percent of these patients had a report of “parasomnias,” which were not further specified. Two
other groups also found an increased overall prevalence of
parasomnias, which included SW and NT in association with
ADHD.78,79
In a recently published paper Silvestri et al75 interviewed 42
newly diagnosed, untreated ADHD children and their parents.
The children were then studied polysomnographically. There
was a 50% prevalence of Disorders of Partial Arousal on clinical interview (28.5% CA, 47.6% SW, 38% NT). On video-PSG,
CA were recorded in 45.2% of their patients, SW in 2.3%, and
NT in 4.7%. One patient reported frequent SW episodes, had
a CA on video-PSG and later exhibited subclinical REM sleep
behavior disorder, thus meeting criteria for parasomnia overlap
disorder. In two children (10.5% of DOA + ADHD patients)
who displayed confusional arousals on PSG, Silvestri et al. also
recorded, as separate events, nocturnal hypermotor, atypical
rolandic seizures. Both children had good evidence of interictal epileptiform discharges (IEDs) on right centro-temporal
and right centro-parietal-occipital regions respectively. Several
other patients (53.1%) in the ADHD sample had IEDs (28.2%
rolandic spikes, 12.5% frontal spikes, 9.3% temporal occipital spikes, and 2.3% generalized abnormalities), accounting for
Disorders of Partial Arousal
Disorders of Partial Arousal (DOA) consist of complex behaviours arising out of stage N3 that are outside the conscious
awareness of the individual. Patients with DOA are difficult to
arouse and have little recollection of the events the next day.
Subjects with DOA may walk (sleep walking- SW), talk in a
confused way (Confusional arousals- CA) or run in a confused
terror while screaming (Sleep Terrors- ST or Night TerrorsNT). Children usually outgrow DOA but DOA may recur in
adulthood under conditions of emotional or physical stress.73-82
ADHD in Disorders of Partial Arousal
To our knowledge, there are no studies looking at the prevalence of ADHD symptoms in patients with disorders of partial
arousal.
Journal of Clinical Sleep Medicine, Vol. 4, No. 6, 2008
597
AS Walters, R Silvestri, M Zucconi et al
42% of the DOA positive group. One more patient within the
whole sample of 42 ADHD children had nocturnal seizures but
did not report nor show any evidence of DOA on PSG.
Of course, it is well known that frontal lobe epilepsy may
mimic Disorders of Partial Arousal. However, despite the large
number of patients in this series who had both interictal discharges as well as complex behaviors during sleep, the authors
looked carefully for ictal discharges during the behaviors and did
not find them. In addition, the complex behaviors did not have
the stereotypy often found with seizures. The authors, therefore,
conclude that the majority of these ADHD patients had both epileptogenic interictal discharges as well as true Disorders of Partial Arousal. The possibility of misdiagnosing true ictal events as
parasomnias has been raised by several authors, especially when
episodes of confusion accompany frontal or temporal lobe epilepsy80 or epileptic nocturnal wondering.81 Also Disorders of Partial Arousal could express a liability to future seizure occurrence
in predisposed children who later in life could develop frontal or
temporal lobe epilepsy.82 Thus, it is no surprise that in the sample
of Silvestri et al, sleepwalking was associated with the presence
of nocturnal seizures and night terrors with frontal IEDs.
The authors gave levetiracetam 750 to 1000 mg per day to
ADHD children with nocturnal seizures, or RLS (26% of the
whole sample) and/or IEDs. This proved effective not only in
controlling seizures and RLS symptoms but also, unexpectedly,
in controlling Disorders of Partial Arousal. Levetiracetam also
reduced the frequency of IEDs by over 50% during a follow-up
period ranging from 12 to 24 months. There were only minimal
and tolerable side effects that subsided over time.
Summary: Despite scanty reports on Disorders of Partial
Arousal in ADHD, this type of parasomnia seems to be quite
prevalent in ADHD, and probably depends on chronic sleep
deprivation via sleep fragmentation due to multiple arousals.
Disorders of Partial Arousal frequently coexist with IEDs, but
less so with nocturnal seizures. Levetiracetam exerts a positive
overall effect not only upon epilepsy but also upon IEDs and
Disorders of Partial Arousal. The reverse prevalence, i.e., the
prevalence of ADHD in Disorders of Partial Arousal remains
to be studied.
future investigations should explore whether narcolepsy is characterized by paradoxical hyperactivity, whether ADHD patients
have a higher prevalence of narcolepsy, and whether patients
with DOA more frequently have ADHD symptoms
Abbreviations
ADHD
iADHD
hADHD
RMD
DSPS
DOA
RLS/PLMS
OSA
IED
NT
SW
CA
Acknowledgment
We would like to thank Stephany Fulda for her helpful comments on this manuscript.
Disclosure Statement
This was not an industry supported study. Dr. Walters has
received research support from Schwanz Pharma, BoehringerIngelheim, GlaxoSmithKline, Kyowa, and Xenoport; is on the
speaker’s bureau for Boehringer Ingelheim and GlaxoSmithKline; and is on the advisory board of Schwanz Pharma, Boehringer-Ingelheim, GlaxoSmithKline, Orion, Kyowa, and Xenoport. The other authors have indicated no financial conflicts of
interest.
REFERENCES
1.
Conclusions
2.
ADHD symptoms occur frequently in the setting of several
specific sleep disorders and vice versa. We would recommend
that clinicians be aware of the potential connection between
ADHD and the specific sleep disorders mentioned. We have
two general recommendations. First, because the various sleep
disorders mentioned more frequently have symptoms of ADHD
than control populations, we recommend that patients with
these sleep disorders be queried about the symptoms of ADHD.
Second, since ADHD patients more frequently have symptoms
of the various sleep disorders in question, we also recommend
that patients with ADHD be queried about the sleep disorders
in question. If these sleep disorders are present in patients with
ADHD, they should be addressed. In addition, there remains
the possibility that treatment of the associated sleep disorder
may lead to adjunctive improvement of the ADHD symptoms
in conjunction with stimulant therapy
In addition to strengthening already established connections,
Journal of Clinical Sleep Medicine, Vol. 4, No. 6, 2008
attention deficit hyperactivity disorder
Inattentive ADHD
Hyperactive ADHD
rhythmic movement disorder
delayed sleep phase syndrome
Disorders of Partial Arousal
restless legs syndrome/periodic limb movements in sleep
obstructive sleep apnea
interictal discharges
night terrors
sleepwalking
confusional arousals
3.
4.
5.
6.
7.
8.
9.
598
Oosterloo M, Lammers GJ, Overeem S, et al. Possible confusion
between primary hypersomnia and adult attention-deficit/hyperactivity disorder. Psychiatry Res 2006;143:293-7.
Rieger M, Mayer G, Gauggei S. Attention deficits in patients with
narcolepsy. Sleep 2003;26:36-43.
Schneider C, Fulda S, Schulz H. Daytime variation in performance and tiredness/sleepiness ratings in patients with insomnia, narcolepsy, sleep apnea and normal controls. J Sleep Res
2004;13:373-83.
Naumann A, Daum I. Narcolepsy: pathophysiology and neuropsychological changes. Behav Neurol 2003;14:89-98.
Schulz H, Wilde-Frenz J. The disturbance of cognitive processes
in narcolepsy. J Sleep Res 1995;4:10-4.
Naumann A, Bellebaum C, Daum I. Cognitive deficits in narcolepsy. J Sleep Res 2006;15:329-38.
Hood B, Bruck B. Sleepiness and performance in narcolepsy. J
Sleep Res 1996;5:128-34.
Fronczek R, Middelkoop HA, van Dijk JG, et al. Focusing on vigilance instead of sleepiness in the assessment of narcolepsy: high
sensitivity of the Sustained Attention to Response Task (SART).
Sleep 2006;29:187-91.
Findley LJ, Suratt PM, Dinges DF. Time-on-task decrements in
Review of the Relationship between ADHD and Specific Sleep Disorders
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
“steer clear” performance of patients with sleep apnea and narcolepsy. Sleep 1999;22:804-9.
Naumann A, Bierbrauer J, Przuntek H, et al. Attentive and preattentive processing in narcolepsy as revealed by event-related
potentials (ERPs). Neuroreport 2001;12:2807-11.
Golan N, Shahar E, Ravid S, et al. Sleep disorders and daytime
sleepiness in children with attention-deficit/hyperactive disorder.
Sleep 2004;27:261-6.
Lecendreux M, Konofal E, Bouvard M, et al. Sleep and alertness in
children with ADHD. J Child Psychol Psychiatry 2000;41:803-12.
Cortese S, Maffeis C, Konofal E. Patient reports of sleep/alertness
problems and ADHD symptoms in a sample of obese adolescents.
J Psychosom Res 2007;63:587-90.
International Classification of Sleep Disorders. Diagnostic and
Coding Manual Second Edition. Westchester, IL: American
Academy of Sleep Medicine, pages; 2005:193-5.
Dyken ME, Lin-Dyken DC, Yamada T. Diagnosing rhythmic
movement disorder with video-polysomnography. Pediatr Neurol
1997; 16: 37-41,
Stepanova I, Nevsimalova S, Hanusova J. Rhythmic movement
disorder in sleep persisting into childhood and adulthood. Sleep
2005;28:851-7.
Simonds JF, Parraga H. Sleep behaviors and disorders in children
and adolescents evaluated at psychiatric clinics. J Dev Behav Pediatr 1984;5:6-10.
Dahl RE, Pelham WE, Wierson M. the role of sleep disturbances
in attention deficit disorder symptoms: a case study. J Pediatr Psychol 1991;16:229-39.
Chandrashekariah R, Mulkanoor S, Couvadelli B, Walters A. Relationship between delayed sleep phase syndrome (DSPS), disorders of partial arousal (night terrors, sleep walking and confusional arousals) (DOA) and Attenion Deficit Hyperactivity Disorder
(ADHD), Seton Hall School of Graduate Medical Education Research Day. 19th Annual Research Colloquium. Abstract May 9,
2008;19: 8.
Gruber R, Sadeh A, Raviv A. Instability of sleep patterns in children with attention-deficit/hyperactivity disorder. J Am Acad
Child Adolesc Psychiatry 2000;39:495-501.
Van der Heijden KB, Smits MG, van Someren EJ et al. Idiopathic
chronic sleep onset insomnia in attention-deficit/hyperactivity disorder: a circadian rhythm sleep disorder. Chronobiol Int
2005;22:559-70.
Rybak YE, McNeely HE, Mackenzie BE et al. An open trial of
light therapy in adult attention-deficit/hyperactivity disorder. J
Clin Psychiatry 2006;67:1527-35.
Allen RP, Picchietti D, Hening WA, et al. Restless legs syndrome:
diagnostic criteria, special considerations, and epidemiology. A
report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med
2003;4:101-19.
Walters AS, Picchietti DL, Ehrenberg BL, et al. Restless
legs syndrome in childhood and adolescence. Pediatr Neurol
1994;11:241-5.
Picchietti D, Allen RP, Walters AS, Davidson JE, Myers A, Ferini-Strambi L. Restless legs syndrome: prevalence and impact
in children and adolescents -- The Peds REST study. Pediatrics
2007;120:253-66.
American Academy of Sleep Medicine. The international classification of sleep disorders. diagnostic and coding manual. 2nd
edition. Westchester, IL: American Academy of Sleep Medicine;
2005:182-6.
Cortese S, Konofal E, Yateman N, et al. Sleep and alertness in
children with attention-deficit-hyperactivity disorder: a systematic review of the literature. Sleep 2006;29:504-11.
Mindell JA, Owens JA. Diagnosis and management of sleep
problems. Lippincott Williams & Wilkins; 2003.
Journal of Clinical Sleep Medicine, Vol. 4, No. 6, 2008
29. Cortese S, Konofal E, Lecendreux M, et al. Restless legs syndrome
and ADHD: a review of the literature. Sleep 2005;28:1007-13.
30. Konofal E, Lecendreux M, Arnulf I, et al. Restless Legs Syndrome and serum ferritin levels in ADHD children. Sleep
2003;26:A136.
31. Picchietti DL, England SJ, Walters AS, et al. Periodic limb movement disorder and restless legs syndrome in children with attentiondeficit hyperactivity disorder. J Child Neurol 1998;13:588-94.
32. Chervin RD, Dillon JE, Bassetti C, et al. Symptoms of sleep
disorders, inattention, and hyperactivity in children. Sleep
1997;20:1185-92.
33. Chervin RD, Archbold KH, Dillon JE, et al. Associations between
symptoms of inattention, hyperactivity, restless legs, and periodic
leg movements. Sleep 2002;25:213-8.
34. Harnish MJ, Boyer S, Kukas L, et al. The relationship between
sleep disorders and attention deficit hyperactivity disorder
(ADHD): objective findings. Sleep 2001;24:A14.
35. Wagner ML, Walters AS, Fisher BC. Symptoms of attention-deficit/hyperactivity disorder in adults with restless legs syndrome.
Sleep 2004;27:1499-1504.
36. Kotagal S, Silber MH. Childhood-onset restless legs syndrome.
Ann Neurol 2004;56:803-7.
37. Zak R, Fisher B, Moss N, Couvadelli B, Walters A. Prevalence of
restless legs syndrome (RLS) in subjects with adult ADHD. Sleep
2007;30:A280.
38. Gamaldo CR, Benbrook AR, Allen RP, Scott JA, Hening WA,
Earlely CJ. Childhood and adult factors associated with restless
legs syndrome diagnosis. Sleep Med 2007;8:716-22.
39. Picchietti DL, Underwood DJ, Farris WA, et al. Further studies
on periodic limb movement disorder and restless legs syndrome
in attention deficit hyperactivity disorder children. Mov Disord
1999;14:1000-7.
40. Martinez S, Guilleminault C. Periodic leg movements in prepubertal children with sleep disturbance. Dev Med Child Neurol
2004;46:765-70.
41. Golan N, Shahar E, Ravid S, et al. Sleep disorders and daytime
sleepiness in children with attention deficit/hyperactivity disorder. Sleep 2004;27:261-6.
42. Crabtree VM, Ivanenko A, O’Brien LM, et al. Periodic limb movement disorder of sleep in children. J Sleep Res 2003;12;73-81.
43. Picchietti DL, Walters AS. Moderate to severe periodic limb
movement disorder in childhood and adolescence. Sleep
1999;22:297-300.
44. Gaultney JF, Terrell DF, Gingras JL. Parent-reported periodic
limb movement, sleep disordered breathing, bedtime resistance
behaviors, and ADHD. Behav Sleep Med. 2005;3:32-43.
45. Sadeh A, Pergamin L, Bar-Haim Y. Sleep in children with attention-deficit-hyperactivity disorder: A meta-analysis of polysomnographic studies. Sleep Med Rev 2006;10:381-8.
46. Weinberg WA, Harper CR. Vigilance and its disorders. Neurol
Clin 1993;11:59-78.
47. Miano S, Donfrancesco R, Bruni O. et al. NREM sleep instability
is reduced in children with attention-deficit/hyperactivity disorder. Sleep 2006;29:797-803.
48. Solanto MV. Dopamine dysfunction in AD/HD: integrating clinical and basic neuroscience research. Behav Brain Res
2002;130:65-71.
49. Trenkwalder C, Paulus W, Walters AS. The restless legs syndrome. Lancet Neurol 2005;4:465-75.
50. Konofal E, Lecendreux M, Arnulf I, et al. Iron deficiency in children with attention-deficit/hyperactivity disorder. Arch Pediatr
Adolesc Med 2004;158:1113-5.
51. Connor JR, Boyer PJ, Menzies SL, et al. Neuropathological examination suggests impaired brain iron acquisition in restless legs
syndrome. Neurology 2003;61:304-9.
599
AS Walters, R Silvestri, M Zucconi et al
52. Earley CJ, Connor JR, Beard JL, et al. Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome.
Neurology 2000;54:1698-1700
53. Walters AS, Mandelbaum DE, Lewin DS, et al. Dopaminergic
therapy in children with restless legs/periodic limb movements in
sleep and ADHD. Dopaminergic Therapy Study Group. Pediatr
Neurol 2000;22:182-6.
54. Konofal E, Arnulf I, Lecendreux M, et al. Ropinirole in a child
with attention-deficit hyperactivity disorder and restless legs syndrome. Pediatr Neurol 2005; 32:350-1.
55. Konofal E, Lecendreux M, Deron J, et al. Effects of Iron supplementation on attention deficit hyperactivity disorder in children.
Pediatr Neurol 2008; 38:20-6.
56. Konofal E, Cortese S. Restless legs syndrome and attention-deficit/hyperactivity disorder. Ann Neurol 2005;58:341-2.
57. Picchietti DL. Is iron deficiency an underlying cause of pediatric
restless legs syndrome and of attention-deficit/hyperactivity disorder? Sleep Med 2007;8:693-4.
58. Chervin RD, Archbold KH. Hyperactivity and polysomnographic
findings in children evaluated for sleep disorder breathing. Sleep
2001;24:313-20.
59. O’Brien LM, Holbrood CR, Mervis CB, et al. Sleep and neurobehavioural characteristics of 5 to 7 year old children with parentally reported symptoms of attention-deficit/hyperactive disorder.
Pediatrics 2003;111:554-63.
60. O’ Brien LM, Ivaneko A, Crabtree VM, Holbrook CR, et al. Sleep
disturbances in children with attention deficit hyperactivity disorder. Pediatr Res 2003;54:237-43.
61. Beebe DW, Gozal D. Obstructive sleep apnea and the prefrontal
cortex: towards a comprehensive model linking nocturnal upper
airway obstruction to daytime cognitive and behavioural deficits.
J Sleep Res 2002;11:1-16.
62. Avior G, Fishman G, Leor A, Sivan Y, Kaysar N, Derowe A. The
effect of tonsillectomy and adenoidectomy on inattention and impulsivity as measured by the test of variables of attention (TOVA)
in children with obstructive sleep apnea syndrome. Otolaryngol
Head Neck Surg 2004;131:367-71.
63. Guilleminault C, Li K, Khramtsov A, Relayo R, Martinez S. Sleep
disordered breathing: surgical outcomes in prepubertal children.
Laryngoscope 2004;114:132-7.
64. Li HY, Huang YS, Chen NH, Fang TJ, Lee LA. Impact of adenotonsillectomy on behaviour in children with sleep-disordered
breathing. Laryngoscope 2006;116:1142-7.
65. Chervin RD, Archbold KH, Dillon JE, et al. Inattention, hyperactivity and symptoms of sleep disordered breathing. Pediatrics
2002;109:449-56.
66. Goodwin JL, Babar SI, Kaemingk KL, et al. Symptoms related
to sleep-disordered breathing in white and Hispanic children:
the Tucson Children’s assessment of sleep apnea study. Chest
2003;124:196-203.
Journal of Clinical Sleep Medicine, Vol. 4, No. 6, 2008
67. Huang YS, Chen NH, Ly HY, Wu YY, Chao CC, Guilleminault
C. Sleep disorders in Taiwanese children with attention deficit/
hyperactivity disorder. J Sleep Res 2004;13:269-77.
68. Huang YS, Guilleminault C, Li HY, Yang CM, Wu YY, Chen NH.
Attention-deficit/hyperactivity disorder with obstructive sleep apnea: a treatment study. Sleep Med 2007;818-30.
69. Sangal RB, Owens J, Sangal J. Patients with attention-deficit/
hyperactivity disorder without observed apneic episodes in sleep
or daytime sleepiness have normal sleep on Polysomnography.
Sleep 2005;28:1143-8.
70. Cooper J, Tyler L, Wallace I, Burgess KR. No evidence of sleep
apnea in children with attention deficit hyperactivity disorder.
Clin Pediatr 2004;43:609-14.
71. Chervin R. How many children with ADHD have sleep apnea or periodic leg movements on polysomnography. Sleep
2005;28:1041-2.
72. Guilleminault C, Korobkin R, Winkle R. A review of 50 children
with obstructive sleep apnea syndrome. Lung 1981;159:275-87.
73. Holtmann M, Becker K, Kentner-Figura B, Schimdt MH. Increased frequency of rolandic spikes in ADHD children. Epilepsia 2003;44:1241-4.
74. Duane DD. Increased frequency of rolandic spikes in ADHD children. Epilepsia 2004; 45: 564-5;
75. Silvestri R, Gagliano A, Calarese T, et al. Ictal and interictal EEG
abnormalities in ADHD children recorded over night by videopolysomnography. Epilepsy Res 2007;75:130-7.
76. Ishii T, Takahashi O, Kawamura Y, Ohta T. Comorbidity in attention deficit-hyperactivity disorder. Psychiatry Clin Neurosci
2003;57:457-63.
77. Gau SSF, Kessler RC, Tseng W-L, et al. Association between
sleep problems and symptoms of Attention-Deficit/Hyperactivity
Disorder in young adults. Sleep 2007;30:195-201.
78. Gau SS. Prevalence of sleep problems and their association with
inattention/hyperactivity among children aged 6-15 in Taiwan. J
Sleep Res 2006;15:403-14.
79. Kraenz S, Fricke L, Wiater A, Mitschke A, Breuer U, Lehmkuhl G.
Prevalence and stress factors of sleep disorders in children starting
school. Prax Kinderpsychol Kinderpsychiatr 2004;53:3-18.
80. Silvestri R and Bromfield E. Recurrent nightmares and disorders of
arousal in temporal lobe epilepsy Brain Res Bull 2004;63:369-76.
81. Gaggero R, Devescovi R, Nobili L, Baglietto MG, Zucconi
M, Schinardi A. Benign parasomnias and nocturnal frontal
epilepsy: differential diagnosis in a case report. J Child Neurol
2001;16:628-31.
82. Silvestri R, De Domenico P, Mento G, Laganà A, Di Perri R.
Epileptic Seizures in subjects previously affected by disorders of
arousal. Neurophysiol Clin 1995;25:19-27.
600
AS Walters, R Silvestri, M Zucconi et al
Review of the Relationship between ADHD and Specific Sleep Disorders
Study
Diagnosis
Study design
No of Patients
Age
Method
Intervention
Results
Journal
Naumann and
Daum
Narcolepsy vs
Controls
Review of
Case Control
Studies
Review— group
sizes vary
Review—Age
Groups vary
Review of Case
Control Studies
None
Difficulties with
memory (response
latency, word
recall, estimation of
frequency), attention
(Wilkinson auditory
vigilance task, Strub
and Black’s list
of letters, 60-min
auditory vigilance
test, 10-min choice
reaction test, 20min digit symbol
substitution test),
executive function
(Sternberg’s STM
Scanning task).
However, these kinds
of deficits were not
found in all studies.
Behav Neurol
2003
Schneider et al
Narcolepsy, OSA,
psychophysiologic
insomnia, controls
Case-control
10 in each of 4
groups
Avg age 52.7 y
CFF, Visual line
tracking test, VAS,
TSS
None
Defects in alertness,
selective attention in
narcolepsy, OSA
J Sleep Res 2004
Schulz and WildeFrenz
Narcolepsy vs
controls
Case control
10 narcolepsy
10 controls
Avg age 42 y
both groups
CFF (vigilance
test)
None
Narcolepsy worse
than controls
J Sleep Res 1995
Naumann et al
Narcolepsy vs
controls
Case control
15 narcolepsy
15 controls
38.3 y
narcolepsy, 38.8
y controls
Attention, memory,
executive control
tasks
None
Difficulties with
executive control in
narcolepsy
J Sleep Res 2006
Hood and Bruck
Narcolepsy vs
controls
Case control
8 narcolepsy
8 controls
Narcolepsy
53 y, Controls
age- and sexmatched
Tasks of automatic,
attentional and
complex cognitive
functioning
None
Level of arousal
determines level of
performance
J Sleep Res 1996
Naumann et al
Narcolepsy vs
controls
Case control
12 narcolepsy 12
controls
41.3 y
narcolepsy, 41.5
y controls
P 300, MMN
None
Differences in ERPs
Neuroreport
2001
Findley et al
Narcolepsy, OSA
Case control
31 OSA, 16
narcolepsy, 14
controls
45 y OSA, 38 y
narcolepsy, 43 y
controls
Number of
simulated car
crashes
None
Narcolepsy crashes
4 x OSA and 100 x
controls
Sleep 1999
Fronczek et al.
Narcolepsy
Case control
15 narcolepsy
15 controls
Adults
SART
None
Difficulties with
SART in narcolepsy
Sleep 2006
Rieger et al
ADHD in narcolepsy
Case control
19 narcolepsy, 20
controls
Mean age 40 y
both groups
Matrices of
Attention
None
Deficits in divided
and flexible
attention but not
other measures of
attention
Sleep 2003
Lecendreux et al
Hypersomnia in
ADHD
Case control
30 ADHD, 22
controls
5-10 yrs
MSLT, CPRS,
CTRS
None
Shorter Sleep
latencies for ADHD
J Child Psychol
Psychiatry 2000
Sadeh et al
PLMS in ADHD
Meta-analysis
227 ADHD vs
132 controls
3.5-16
PSG
No
PLMS more
common in ADHD
Sleep Med Rev,
2006
Chervin et al
Snoring in ADHD
Crosssectional
survey
143
2-18 y
Questionnaire
None
Snoring more
common in ADHD
(P< .01)
Sleep 1997
Cortese et al
SDB, EDS,
movement in ADHD
Meta-analysis
13 studies
140 ADHD vs 69
controls
6-15
PSG, MSLT
No
More SDB, EDS,
movement in ADHD
Sleep 2006
Konofal et al
ADHD+RLS vs
controls vs ADHD
alone
Case control
12 ADHD + RLS
vs 10 controls vs
10 ADHD alone
5-8
RLS criteria,
CPRS, ferritin
No
Lowest ferritin in
ADHD+RLS vs
ADHD alone vs
controls
Sleep Med, 2007
Konofal et al
ADHD (with or
without RLS)
Clinical trial
DBPLC
18 ferrous sulfate
vs 5 placebo
5-8
ADHD RS,
CPRS,CTRS,
ferritin
Ferrous sulfate (80
mg/d) 12 weeks
Significant
effectiveness on
ADHD
Pediatr Neurol,
2008
O’Brien et al
OSA in ADHD
Crosssectional study
5728 children in
public schools
5-7
Questionnaire,
PSG,
neurocognitive
tests
No
SDB more prevalent
among children with
mild symptoms of
ADHD (26%) than
severe ADHD (5%)
than controls (5%)..
Pediatrics 2003
Cooper et al
SDB in ADHD
Case control
18 ADHD vs 20
non-ADHD
4-16 y
PSG
No
No significant effect
size
Clin Pediatr
2004
Chervin et al.
RLS in ADHD
Crosssectional
survey
866
2-13.9 y
PSQ
None
RLS more
commonly
associated with
hyperactivity and
inattention
Sleep 2002
Journal of Clinical Sleep Medicine, Vol. 4, No. 6, 2008
S1
AS Walters, R Silvestri, M Zucconi et al
Review of the Relationship between ADHD and Specific Sleep Disorders
Study
Diagnosis
Study design
No of Patients
Age
Method
Intervention
Results
Journal
Gaultney et al.
PLMS in ADHD
Crosssectional
survey
283 school
children
7-14 y
PSQ and own
questionnaire
None
PLMS more
commonly
associated with
ADHD than SDB
with ADHD
Behav Sleep
Med 2005
Huang et al
SDB and PLMS in
ADHD
Case Control
88 ADHD vs 27
Controls
Mean 8.6
PSG, DSM-IV
criteria for ADHD
No
AHI >1 in 56.8%
of ADHD group
and 3.7% of control
group, PLMS index
>5/h in 10.2% of
ADHD and no
controls
J Sleep Res 2004
Huang et al
3 groups Children
with ADHD and AHI
>1<5
Treatment
66 total with
ADHD
6-12
PSG, TOVA,
WISC-III, CBCL,
ENT evaluation
T & A versus
methylphenidate
versus no Rx.
Surgery improved
ADHD more than
methylphenidate or
no treatment
Sleep Med 2007
Li et al
SDB
Treatment
40 SDB with
adenotonsillar
hypertrophy
Mean 8.4
PSG, TOVAs,
Child Behavioral
Checklist
A&T
A & T improved
TOVA score but no
correlation between
AHI and TOVA
changes
Laryngoscope
2006
Goodwin et al
SDB
Crosssectional
Survey
1494
4-11
Questionnaire
Not reported
Association of
learning problems
with SDB symptoms
Chest 2003
Melendres et al
Suspected SDB and
controls
Case control
108 with
suspected SDB,
72 controls
SDB Mean 7 ±
4 y and controls
8±4y
PSG, ESS, CASQ
Not reported
Children with SDB
sleepier and more
hyperactive than
controls
Pediatrics 2004
Sangal et al
ADHD without
clinical SDB
Crosssectional study
40
6-14
PSG, ADHD-RS
No drug treatment
No OSA in ADHD
without clinical
symptoms of SDB.
Sleep 2005
Picchietti et al
ADHD in RLS
Crosssectional
survey
10,523 families
8-17 y
Survey
None
ADHD more
common in RLS
Pediatrics 2007
Picchietti et al
PLMS in ADHD
Case control
study
69 patients and
38 controls
2-15 y
Survey and PSG
No
PLMS more
common in children
with ADHD
J Child Neurol
1998
Picchietti et al
PLMS in ADHD
Case control
14 ADHD, 10
controls
5-12 y
PSG
None
PLMS more
common in ADHD
than controls (p <
0.0015)
Mov Disord
1999
Picchietti and
Walters
ADHD in PLMS
Crosssectional study
of ADHD
prevalence
129
<20 y
DSM-IV criteria
for ADHD
None
ADHD very
common in children
with PLMS
Sleep 1999
Wagner et al
ADHD in RLS
Case control
62 RLS, 77
controls, 32
insomnia
Avg age 68 y
DSM-IV criteria
for ADHD, Brown
Adult ADHD scale
None
ADHD more
common in adult
RLS (26%) than
in insomnia (6%)
or normal controls
(5%)
Sleep 2004
Gamaldo et al
ADHD in RLS
Crosssectional
survey
973 family
members of RLS
probands
Avg Age 47 y
Retrospective
recollection of
inattentiveness as
child
None
No association
between ADHD and
RLS
Sleep Med 2007
Martinez and
Guilleminault
PLMS in ADHD
Crosssectional
study in sleep
disordered
children
252
15 months–11 y
PSG
None
7/11 children with
ADHD had PLMS
Dev Med Child
Neurol 2004
Golan et al.
SDB and PLMS in
ADHD
Case control
study
34 ADHD, 32
controls
ADHD avg age
12.4 y, controls
12 y
PSG
None
50% of children with
ADHD had SDB as
opposed to 22% of
controls (p <0.05).
15% of ADHD
group had PLMS vs
none of the controls.
Sleep 2004
Crabtree et al
PLMS and SDB in
ADHD
Retrospective
review of PSG
studies
69 with ADHD
Avg age 8.3 y
PSG
None
PLMS in 36%, SDB
in 7%
Clin Pediatr
2003
Crabtree et al
ADHD in PLMS
Crosssectional
Study
90 with PLMS
5-7 y
PSG
None
44% of those with
PLMS had ADHD
J Sleep Res 2003
Kotagal and
Silber
ADHD in RLS
Crosssectional
survey
538 subjects
from sleep
disorder center
Children <18 y
Question on
Inattentiveness
None
25% of subjects with
inattentiveness
Ann Neurol
2004
Journal of Clinical Sleep Medicine, Vol. 4, No. 6, 2008
S2
AS Walters, R Silvestri, M Zucconi et al
Review of the Relationship between ADHD and Specific Sleep Disorders
Study
Diagnosis
Study design
No of Patients
Age
Method
Intervention
Results
Journal
Chervin and
Archibold
Relationship of
SDB and PLMS to
Hyperactivity
Case control
59 SDB, 54
controls
2-18 y
PSG
None
PLMS but not SDB
showed a linear
association with
hyperactivity
Sleep 2001
Oosterloo et al
ADHD in
Hypersomnia and
Hypersomnia in
ADHD
Crosssectional
survey
67 narcolepsy, 7
IHS, 61 ADHD
48 y
hypersomnia,
35 y ADHD
ADHD rating
scale, ESS
None
18.9% of
hypersomnia patients
have ADHD, 37.7%
of ADHD patients
have hypersomnia
Psychiatry Res
2006
Dyken et al
ADHD in RMD
Observational
7 with RMD
1 -12 y
PSG, ADHD
by past medical
history
None
3 of 7 children with
RMD by PSG had
ADHD
Pediatr Neurol
1997
Stepanova et al
ADHD in RMD
Observational
10 RMD
7-24 y
PSG, DSM-IV
criteria for ADHD
None
6 of 10 subjects had
ADHD
Sleep 2005
Simonds and
Parraga
RMD (head banging)
in ADHD
Case control
150 psychiatric
problems, 309
controls
4-18 y
DSM-III for
ADHD, at least
one head banging
episode in last 6
months
None
6 of 14 patients
with RMD had head
banging and none of
controls.
J Dev Behav
Pediatr 1984
Chandrashekariah
et al
ADHD in DSPS
Observational
5 DSPS
Adults
DSM-IV for
ADHD
None
None met criteria for
ADHD
Seton Hall
Research
Abstracts 2008
Dahl et al
Patient with ADHD
and DSPS
Treatment
One patient
with ADHD and
DSPS
10 y
Measured
improvement in
both conditions
Chronotherapy
Improvement in
DSPS and ADHD
J Pediatr Psychol
1991
Van der Heijden
et al
DSPS in ADHD
Case Control
87 ADHD with
sleep onset
insomnia, 33
ADHD with
no sleep onset
insomnia
6-12 y
Salivary melatonin,
wake up times
None
DLMO and wake up
times much later in
ADHD patients with
sleep onset insomnia
suggesting DSPS
Chronobiol Int
2005
Rybak et al
ADHD
Treatment
29
18-60 y
DSM-IV,
Adult Brown,
Conners, Horne
Ostberg morning
eveningness
questionnaire,
Therapeutic study.
Bright light therapy
Improvement in
ADHD and phase
advance of sleep
time suggesting
DSPS
J Clin Psychiatry
2006
Ishii et al
ADHD
Crosssectional
survey
68
9.7
Parental and
pediatric interview
No intervention
2.9% DPA in ADHD
Psychiatry Clin
Neurosci 2003
Gau et al
Prevalence of
Historical Sleep
Disorders in ADHD
vs non-ADHD
Cross
sectional
survey
2284 first-year
college students
18-20 y
Questionnaires,
ADHD scale
None
Snoring,
sleepwalking, ST
more common in
ADHD
Sleep 2007
Gau et al
Prevalence of
historical sleep
disorders in ADHD
vs non-ADHD
Crosssectional
survey
2463 first
through ninth
graders
6-15 y
CPRS, CTRS,
CHQ, Sleep Habits
Questionnaire
None
PLMS, SDB,
parasomnias more
common in ADHD
J Sleep Res 2006
Kraenz et al
ADHD in
Parasomnia
Survey of
parents of
children
starting school
----------
5-6 y
Comparison of
ADHD symptoms
in parasomnia vs
non-parasomnia
Children
None
Hyperactivity
increased in
parasomnia
Prax
Kinderpsychol
Kinderpsychiatr
2004
Miano et al
ADHD vs controls
Case control
20 ADHD vs 20
controls
9.3
Clinical Interview
and PSG
No intervention
35% parasomnias,
lower CAP rate and
CAP sequences in
ADHD
Sleep 2006
Silvestri et al
ADHD vs controls
Case Control
42
8.9
Clinical interview
and PSG
No intervention
50% DPA in ADHD,
26% RLS in ADHD
Epilepsy Res
2007
Legend: Polysomnography (PSG), Attention Deficit Hyperactivity Disorder Rating Scale (ADHD RS), Conners Parents Rating Scale (CPRS); Conners Teachers Rating Scale (CTRS), Double Blind Placebo Controlled (DBPLC), Test of Variable Attention (TOVA), Adenoidectomy and Tonsillectomy (A&T), Sleep
Disordered Breathing (SDB), Obstructive Sleep Apnea (OSA), Hypopnea Index (AHI), Epworth Sleepiness Scale (ESS), Conners Abbreviated Symptom
Questionnaire (CASQ), Child Behavior Check List (CBCL), Disorders of Partial Arousal (DPA), Cyclic Alternating Pattern (CAP), Idiopathic Hypersomnia
(IHS), Multiple Sleep Latency Test (MSLT), Rhythmic Movement Disorder (RMD), Delayed Sleep Phase Syndrome (DSPS), Chinese Health Questionnaire
(CHQ), Sustained Attention to Response Task (SART), Mismatch Negativity (MMN), Event Related Potentials (ERPs), Critical Flicker Fusion (CFF) Test,
Visual Analogue Scale (VAS), Tiredness Symptoms Scale (TSS), Pediatric Sleep Questionnaire (PSQ), Pediatric Sleep Questionnaire (PSQ)
Journal of Clinical Sleep Medicine, Vol. 4, No. 6, 2008
S3