Transcript Slide 1
Sleep in Children with Neurodevelopmental Disorders:
What Can We Do in the Community Setting?
SHHCC Sleep(y) Rounds
October 22, 2009
Judith Owens MD MPH
Alpert Medical School of Brown University
Disclosures
Grants: Shire, Boehringer-Ingleheim
Speakers Bureau: Lilly, Shire
Consultant/Advisory Board: Lilly, Shire, Isis
Biopolymer, Sanofi-Aventis
The material presented in this lecture has no
relationship with any of these potential conflicts
Off-label use of medications will be discussed
Objectives
Summarize common sleep issues in children with
various neurodevelopmental disorders
Attention Deficit Hyperactivity Disorder
(ADHD)/Tourette Syndrome (TS)
Autism Spectrum Disorders (ASD)
Syndromes: Down, Prader-Willi, Angelman, Williams,
Smith-Magenis
Provide general clinical recommendations for
managing sleep problems in these populations
ADHD: Background
Most common childhood psychiatric condition
Affects 3-5% (8-10% school-aged; 3-6% adults)
ADHD subtypes
Predominantly hyperactive-impulsive (<15%)
Predominantly inattentive (20-30%)
Combined subtype (50-75%)
M:F
4:1 (hyperactive/impulsive); 2:1 (Inattentive);
9:1 (clinical pop)
60% of patients diagnosed in childhood continue
to exhibit symptoms into adulthood
Sleep in ADHD: Subjective
Measures
Measure observations of sleep behavior in naturalistic
settings (sleep quantity/quality, sleep problems,
symptoms sleep disorders (ie, SDB, RLS)
Parent surveys/interviews, sleep diaries, self-report
Sleep problems in 25-50%
Increase in wide variety sleep problems compared to healthy and
psychiatric control groups; more night-to-night variability
More problematic evening/bedtime behavior
Increase snoring, bruxism, parasomnias, enuresis, PLMs
Sleep in ADHD: Actigraphy
Measures sleep patterns in naturalistic settings over
time
SOL, TIB, SE, NW (frequency, duration), MT, SD
Actigraphy:
No consistent differences in ADHD/controls sleep onset
latency, duration
Variable increased nocturnal activity, awakenings ADHD
Increased night-to-night variability
No differences by ADHD severity, subtype, ODD
Inconsistent med-related differences
Sleep Measures in ADHD
What factors potentially account for the discrepancies
between subjective and objective findings regarding
sleep in children with ADHD?
Parental perception of sleep problems may be heightened
Evening behavior may be qualitatively different
Clinicians may have decreased threshold for identifying sleep
problems
Parents may be primed to report sleep problems concomitant
with ADHD medication
PSG, actigraphy, parent report measure different sleep
parameters
Summary: PSG in ADHD
Meta-analysis
PLMs only significant effect size overall
(d=0.26, p<.05)
Many studies show modest REM
differences; clinical significance?
Summary: Sleep in ADHD
2009 meta-analysis 16 studies ADHD
(exclusion meds/comorbidity) vs controls
10/13 ’87-05; 6/31 ’05-08; N=722
Subjective: increase BR, SOD, NW, DTS,
symptoms SDB
Objective:
PSG: increase sleep stage shifts, AHI;
decrease SE
Actigraphy: increase SOL; decrease SD
Sleep in ADHD:
Intrinsic Impairments?
Impaired sleep
ADHD-related homeostatic dysregulation
(altered sleep drive)
Circadian dysfunction (phase delay)
Studies suggest delayed endogenous circadian
pacemaker in children with ADHD
Sleep onset, morning wake time significantly later
(actigraphy)
Melatonin onset significantly later
Positive response to bedtime dose exogenous
melatonin
Sleep-Alertness Studies in ADHD
Increased daytime sleepiness (MSLT)
No consistent group nocturnal sleep differences sleep
architecture
Decreased mean SOL, more likely to have
SOL<10,<5min
HI fall asleep more quickly
Fall asleep in more naps
Inattentive fall asleep on more naps
Relative risk for falling asleep 1.57 ADHD vs controls
Sleep Disordered Breathing (SDB)
and ADHD
Significant differences in observed sleepiness,
mood, externalizing/internalizing behaviors,
attention, learning difficulties
Academic performance compromised
Less consistent specific neurocognitive deficits
At least partial resolution of deficits posttreatment (T&A)
SDB and ADHD: Clinical Studies
Percent of hyperactive/impulsive children with symptoms
of SDB may be as high as 25%
SDB more likely to resemble “mild” ADHD
Primary snoring as well as OSA at risk for neurobehavioral
deficits
Compared to controls, children scheduled for T&A
More likely to meet ADHD diagnostic criteria (22% vs 7%)
T&A group significant improvement, no between-group differences
1-year post-op; 50% no longer met ADHD criteria
PSG did not predict baseline neurobehavioral impairment nor
correlate with improvement (except sleepiness)
Case Study 1
10-year-old male with mild inattentive symptoms and
declining school performance referred for ADHD
evaluation
Medical history significant for moderate tonsillar
hypertrophy, seasonal allergies, GER, BMI 30
Snores “just like dad,” sweats during sleep
Parents report difficulty in morning waking, occasional
dozing off in school
Case Study 1: Key Points
Severity and onset of ADHD symptoms
Multiple OSA risk factors
OSA symptoms
Presence of daytime sleepiness
RLS/PLMD in Children
RLS clinical diagnosis; PLMD PSG diagnosis
Brief (0.5-10 sec) repetitive jerking movements
of lower extremities at 20-40 sec intervals
during Stage 1 and 2 sleep
Early-onset high hereditability
Iron deficiency (serum ferritin<50) risk
factor
Prevalence “definite” RLS 2% in 8-17yo
Definition (International RLS
Study Group 2003)
Urge to move legs, usually accompanied by
uncomfortable/unpleasant sensations
Urge to move/unpleasant sensations beginning or
worsening periods rest/inactivity
Urge to move/ unpleasant sensations worse or
only occur evening, night
Urge to move/ unpleasant sensations
partially/totally relieved by movement, at least as
long as activity continues
Pediatric definition includes child’s description,
family history, PLMs on PSG
A Child’s Eye View of RLS…
“They (my legs) like feel weird, and
they want to kick” 7 y.o. boy
“OK, I'm in bed, and my legs
really, really hurt. So I say, help,
Mom, I need you.” 7 y.o. boy
“It’s like my legs are wiggly”
8 y.o. boy
“Well, sometimes it feels like little tiny
nails are just lightly poking my legs at
certain times, like whenever I get into
the bed.” 11 y.o. boy
RLS/PLMD and ADHD
44% children with PLMs on PSG with symptoms ADHD
8/32 RLS children with inattentive symptoms
26% adults with RLS have ADHD/symptoms
In clinical samples (literature review) RLS/PLMs more
prevalent in children with ADHD
Up to 44% ADHD children/20% adults have RLS
symptoms
26-64% children with ADHD have PLMI > 5
Treatment case studies suggest response to DA agents, iron
RLS/PLMD and ADHD
Potential mechanisms
Sleep disruption→ADHD symptomatology
Diurnal RLS manifestations mimic ADHD;
nocturnal ADHD symptoms mimic RLS
Common CNS pathology: dopaminergic
dysfunction, iron deficiency
Comorbid ADHD-RLS/PLMD
Case Study 2
12-year-old girl with mostly inattentive symptoms
Medical history of “growing pains,” iron deficiency
anemia
Maternal history of RLS
Complains of difficulty falling asleep and “funny
feelings” in her legs at night, relieved by movement
Bedclothes “all over the place” in the morning;
wakens unrefreshed
Case Study: 2 Key Points
Sleep-onset symptoms suggestive of
RLS
Sleep maintenance symptoms
suggestive of PLMD
Multiple risk factors for RLS/PLMD
Medications and ADHD
Medications used to treat ADHD or comorbid conditions
may affect sleep and wakefulness
Psychostimulants
Subjective and parent reports inconsistent
Objective effects on sleep architecture (PSG)
and other sleep variables (actigraphy) duration
variable; rebound effects
Nonstimulants
Other psychotropics (eg, SSRIs, mood stabilizers);
may also affect REM sleep
Comorbid Disorders
Comorbid disorders may contribute to sleep
problems
Bedtime resistance/sleep onset delay related to
ODD (60%)*, anxiety disorders (30%)*, OCD
Insomnia, early morning awakening related to
depression (10-30%)*
Decreased need for sleep related to
BPD (11-20%)*
*Percent of ADHD patients with comorbid condition.
Case Study 3
8-year-old male with ADHD, combined type and difficulty
falling asleep; currently on Concerta
72 mg taken at 7:00AM
Psychiatric: ODD, mild dyslexia
Previous medications: mixed amphetamine salts
(Adderall XR), dextroamphetamine, methylphenidate
Sleep patterns
Bedtime variable; typically falls asleep past midnight;
“snacks” during the night; awakened
with difficulty at 7:00AM for school
Case Study: 3 Key Points
Role of stimulant medication: type,
dose, rebound
Role of comorbid ODD
Contribution of insufficient sleep to
ADHD
Role of inadequate sleep hygiene
Tourette’s Syndrome (TS)
Characterized by chronic motor/vocal tics
Frequent comorbidities:
ADHD in TS 40-60%; TS in ADHD 10-30%
OCD, anxiety disorders
Subjective increase sleep disturbances,
especially sleep wake transition disorders,
difficulties initiating/maintaining sleep;
increased with comorbid ADHD
PSG in TS
Children/mixed samples:
Decreased TST, SE; increase night wakings
Variable effects architecture:
PSG sleep parameter profiles vary with symptom
complex (ADHD, OCD)?
Variable differences REM parameters
Variable MT; variable association with nocturnal
tics
Autism Spectrum Disorders (ASD)
Autism, Pervasive Developmental Disorder NOS,
Asperger
Definition - neurodevopmental disorders characterized
by:
Impairments social interaction
Communication deficits and severe language delays
Restricted, repetitive, rigid, and stereotypic behaviors and
routines
Majority severe cognitive impairments
Asperger syndrome (AS):
Normal cognitive level
No significant language delay but problems pragmatic
language skills
Sleep Disturbances in ASD:
Subjective
Estimates range from 34 to 89%
Autism 44-89% past or concurrent
Similar rates PDD NOS
Parent/self-report increase sleep onset problems, short
SD
Rates largely independent of IQ
High-IQ (> 55) children with autism have more
sleep problems than normal controls
Normal IQ ASD children have significantly more
sleep problems (p < .002) than normal controls
Sleep Disorders in Children with
Severe Intellectual Disability (ID)
Sleep problems in these children are common
with prevalence rates ranging from 44% to 86%
Majority persist over time
Increased sleep problems with more severe ID
and younger age
More sleep problems in adolescents and young
adults with severe ID with autism vs. severe ID
without autism
Sleep Disturbances in ASD:
Subjective
Most commonly include
Highly irregular sleep-wake cycles
Unusual, problematic sleep routines (often
accompanied by repetitive behaviors)
Difficulty settling, delayed sleep onset
Frequent and prolonged nightwakings
Short sleep duration
Early morning wake times
Possibly parasomnias (sleepwalking, bruxism, RBD)
more common
Sleep Disturbances in ASD:
Subjective
Association with severity daytime
behavior problems, communication
impairments
Increased severity, chronicity, relapse
rate
Significant impact on caregivers
Sleep Problems in ASD: Biological
Etiology
Circadian rhythm abnormalities
Disturbance in melatonin production in autism
Precursor (tryptophan, serotonin) levels
altered
Daytime elevation, decreased amplitude,
nighttime decrease
Anamolies in clock genes; ?motor planning/sleep
Less entrainment by social/environmental cues
Greater sensitivity changes in photoperiod;
?seasonal variations
Sleep Problems in ASD:
Biological Etiology
Secretin hypothesis
Endogenous GI polypeptide; ?role language,
behavior, sleep
Activation inflammatory response system
Increased markers in autism; ?sleep effects
Primary arousal dysfunction; ?altered homeostasis
Dysfunction aminergic (DA, serotonin) pathways
Decreased sleep duration
Sleep Problems in ASD:
Psychosocial Etiology
Learned maladaptive sleep patterns
Anxiety-related; high levels autistic children
Inadequate parent limit-setting
Parents may be more aware of difficulties than
parents of typically developing children
Many patients have more than one etiology
Sleep Disturbances in ASD:
Objective
Discrepancy between parent report of
sleep problems & actigraphy
Adolescents and adults with high
functioning autism
Sleep Latency, Sleep Efficiency, Wake
After Sleep Onset
Down Syndrome
Subjective difficulties with sleep onset (up to 70%)
PSG:
Increased AI, stage shifts
Increased movement arousals, periodic limb movements
Decreased TST, REM (negatively correlated IQ)
Increased SDB
OSA prevalence 30-80%
Risk factors:
Generalized hypotonia
Obesity, central distribution of adipose tissue
Midfacial hypoplasia, glossoptosis
Adenotonsillar hypertrophy
Hypothyroidism
Central sleep apnea, Cheyne-Stokes
Prader-Willi Syndrome
Genetic disorder characterized by
Paternal inherited abn chromo-15 (q11-q13)
FTT, hypotonia (infants)
Hypogonadism, short stature
Hyperphagia/obesity,
MR behavioral problems
Increased prevalence sleep disordered breathing
Rates SDB highly variable (0-100%)
Hypoventilation, obstructive/central sleep apnea esp in REM
Oxygen desaturation; correlated BMI
Severity SDB may correlate with BMI; improvement with weight
loss
Delayed psychomotor development infants assoc with
obstructive rather than central sleep apnea
SDB in PWS
High rates post-op complication T&A
Possible increased risk sudden death GH
therapy
Occurs initial treatment period
Linked OSA, concurrent URI
Prader-Willi Syndrome: EDS
Daytime sleepiness common
Increase subjective complaints; correlated MSLT
MSLT: severe EDS frequent (40% studies
MSOL<5), SOREMPs, increased duration/depth
(SWS) sleep
May occur independently of obesity, SDB
CPAP improves EDS
Generally more severe adults vs children;
increases adolescence
Possible link hypothalamic dysfunction
Angelman Syndrome
Genetic disorder (abn maternal chromo 15 characterized
by severe dev/exp language delays, motor impairments,
seizures, behavioral phenotype (“happy puppet”)
Subjective caregiver report sleep problems 20-80%
Decreased sleep duration, frequent NW
Irregular sleep-wake cycles
Increased younger patients (2-6y); may improve in adolescence
PSG:
Increased SOL, WASO
Decreased REM%, increased SWS
Sleep fragmentation associated with seizures, esp REM
? Increase PLMs
William Syndrome
Deletion chromo 7q11.23, elastin/CNS development effect
Characterized by MR, visual motor deficits, ADHD,
alterations connective/vascular tissue
Subjective sleep complaints inc DIMS, restless sleep
PLMs
16/28 screened symptoms suggestive movement
disorder
PSG N=7 vs controls:
PLMI 14.9 vs 1.9; increased PLMAI
Increased WASO (2x), SWS
No differences respiratory parameters; 1 with SDB
Clinical response clonezapam
Smith-Magenis Syndrome
Genetic syndrome (deletion chromo 17p11.2)
associated with severe developmental delay,
behavioral difficulties including extreme hyperactivity
and aggression
Subjective significant sleep difficulties (60-100%)
Caregivers report difficulty falling asleep, short
sleep duration, frequent and prolonged night
wakings, snoring, daytime sleepiness, nocturnal
enuresis
PSG studies
Early sleep onset/offset with inversion circadian
rhythm of melatonin
Decreased TST, REM
Clinical Issues
Maintain high index of suspicion for sleep
problems
Systematically and regularly screen all
children as part of routine care
Recognize daytime sequelae (mood,
behavior, cognition)
Recognize impact on family functioning
Clinical Issues
Develop a systematic approach to evaluation
Insomnia is a symptom, not a diagnosis; multiple
potential causes
Judicious use diagnostic tools (sleep logs,
actigraphy, PSG)
Consider comorbid sleep diagnoses (OSA and
parasomnias, insomnia and PLMS)
Consider underlying contributing factors (meds,
sensory deficits, nocturnal seizures)
Clinical Issues: Treatment
Avoid the “inevitability/untreatable trap”
Use empirically-supported behavioral
management strategies
Support parents – consider respite care
Consider judicious use of medication in
combination with behavioral therapies
PAY ATTENTION TO SLEEP HYGIENE!
Management of Sleep
Problems
Sleep hygiene1
Sleeping position: GER, immobility
Sleep environment:
Sensory issues: weighted blankets/vests, “white
noise” machines
Temperature dysregulation: absorbent bedding
Safety concerns: fortified cribs
Scheduling: bedtime/waketime, napping,
daytime activities
1Jan et al Pediatrics 2008
Behavioral Insomnia of
Childhood: ICSD-II Definition
Sleep Onset Association subtype
Falling asleep is an extended process that
requires special conditions
Sleep-onset associations are highly problematic
or demanding
In the absence of the associated conditions,
sleep onset is significantly delayed or sleep is
otherwise disrupted
Nighttime awakenings require caregiver
intervention for the child to return to sleep
Behavioral Insomnia of
Childhood: ICSD-II Definition
Limit Setting subtype
The child has difficulty initiating or maintaining
sleep
The child stalls or refuses to go to bed at an
appropriate time or refuses to return to bed
following a nighttime awakening
The caregiver demonstrates insufficient or
inappropriate limit setting to establish
appropriate sleeping behavior in the child
Management BIC: Sleep Onset
Association
Establishment of appropriate sleep onset
associations that will be available to the child
during the night
Consistent, developmentally-appropriate bedtime
routine, transitional objects
Behavioral interventions
Extinction
Graduated extinction
Scheduled awakenings
Management BIC: Limit
Setting
Education and support of parents regarding
developmentally appropriate limit setting
Appropriate consistent bedtime, routine
Clear, concise, and firm bedtime rules with limited
choices
Behavioral interventions
Bedtime fading
Positive reinforcement
“Bedtime pass”
Behavioral Interventions:
Graduated Extinction
Graduated extinction (“sleep training”,
“checking” or “Ferber method”): variety
of techniques in which parents are
typically instructed to ignore bedtime
crying and tantrums for specified periods
of time
Involve gradual shaping of appropriate
behaviors and fading of interventions
Behavioral Interventions:
Graduated Extinction
Put child to bed “drowsy but awake”
Use fixed or progressively longer interval
schedule tailored to the child’s age and
temperament, parental tolerance
Minimize interactions during check-ins that may
reinforce child’s attention-seeking (reassuring,
brief, boring)
Checking method at bedtime only; generalization
to night wakings
Variations on Graduated
Extinction
Parent stays with child at sleep onset, gradually
fades attention, assistance, and presence
Parent sits in chair at sleep onset, gradually
moves chair out of room
Parent sleeps beside child’s bed, gradually moves
bed out of room
Child allowed to sleep on separate bed in
parent’s room during night wakings
Bedtime pass
Other Treatment Issues
Common for crying/protest to briefly intensify
2nd or 3rd night (“extinction burst”)
Avoid intermittent reinforcement (the “lottery
theory”)
Avoid increasing reinforcement during checks
Do not allow child to extend day sleep
Improvement in one week if parents
consistent
Bedtime Fading
Temporarily delay of bedtime to ensure
rapid sleep initiation; bedtime then
moved earlier by small increments (ie,
15 minutes) over successive nights
(“fading”) until pre-established bedtime
goal is achieved
Management of Sleep
Problems
Circadian rhythm disruption
Chronotherapy
Bright light phototherapy
Pharmacologic treatment
Melatonin ASD, ADHD, blind, MR, Rett,
Angelman
Risperidone ASD
Clonidine ADHD
Percent of respondents prescribing
Child Psychiatry Survey: Prescription
Medications in MRDD
80
70
60
50
40
30
20
10
0
MRDD
Owens, unpublished data
Barbituate
Chloral Hydrate
Benzo
Anticonvulsant
Hypnotic
TCA
SSRI
Antihistamine
Antipsychotic
Sedating Antidep
Trazadone
Alpha Agonist
Sleeping Children Around the
World
(SCAW)
What is SCAW?
Registered Canadian charity based in Toronto
founded in 1970 by Murray and Margaret Dryden
Goal: “A world in which every child benefits from
the comfort of a good night’s sleep.”
Mission: Through free-will donations and in
partnership with volunteers, to give bedkits to
needy children in developing countries, thus
helping them to face the challenges of the
coming day.
Scope*
Bangladesh
Chennai
Honduras
Kenya
Kolkata
Mumbai
Togo
Uganda
Sri Lanka
Philippines
Tanzania
SCAW has provided bedkits for more than
one million children
*Less than $2,000 U.S. average per capita income
Bedkits
Mat/mattress
Pillow (pillowcase)
Sheet, blanket/quilt
Insecticide-treated mosquito netting
Clothing: t-shirts, shorts, sweater,
nightclothes, sandals, raincoat
School supplies: workbooks, pencils, crayons,
compass, bookbag, lunchbox
Other: plastic bucket, pitcher, water bottle,
umbrella, plates, cups
Carrying bag
How to Help
Donate bedkits ($35 Canadian funds)
Donate to Investment Account
Purchase greeting cards
Fund raise
Volunteer
Spread the word
www.scaw.org
“The comfort of a bed is a basic right for every child.”
Murray Dryden, founder SCAW
Thanks!
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