The Visual Scoring of Sleep and Arousal in Infants and Children

43 Pages·2007·1.01 MB·English

The Visual Scoring of Sleep and Arousal in Infants and Children
Madeleine Grigg-Damberger, M.D.1; David Gozal, M.D.2; Carole L. Marcus, M.B.B.Ch.3; Stuart F. Quan, M.D.4; Carol L. Rosen, M.D.5; Ronald D. Chervin, M.D.6; Mer-
rill Wise, M.D.7; Daniel L. Picchietti, M.D.8; Stephan H. Sheldon, D.O.9; Conrad Iber, M.D.10
1University of New Mexico School of Medicine, Albuquerque, NM; 2 University of Louisville School of Medicine, Louisville, KY; 3Children’s Hospital
of Philadelphia, University of Pennsylvania, Philadelphia, PA; 4Sleep Disorders Center, University of Arizona, Tucson, AZ ; 5Case Western Reserve
University School of Medicine, Cleveland, OH; 6University of Michigan School of Medicine, Ann Arbor, MI; 7Methodist Healthcare Sleep Disorders
Center, Memphis, TN; 8University of Illinois and Carle Clinic, Urbana, IL; 9Northwestern University, Feinberg School of Medicine, Chicago, IL;
10University of Minnesota, Minneapolis, MN
Abstract: Age is probably the single most crucial factor determining how central (C) EEG derivation. About 50% of sleep spindles within a par-
4
humans sleep. Age and level of vigilance significantly influence the elec- ticular infant’s PSG are asynchronous before 6 months of age, 30% at 1
troencephalogram (EEG) and the polysomnogram (PSG). The Pediatric year. Based on this, we recommend that: 1) sleep spindles be scored as
Task Force provide an evidence-based review of the age-related devel- a polysomnographic signature of NREM stage 2 sleep (N2) at whatever
opment of the polysomnographic features of sleep in neonates, infants, age they are first seen in a PSG, typically present by 2 to 3 months post-
and children, assessing the reliability and validity of these features, and term; 2) identify and score sleep spindles from the frontal and centropa-
assessing alternative methods of measurement. We used this annotated rietal EEG derivations, especially in infants and children younger than
supporting text to develop rules for scoring sleep and arousals in infants 13 years. NREM sleep in an infant or child can be scored if the dominant
and children. A pediatric EEG or PSG can only be determined to be nor- posterior rhythm occupies <50% of a 30-second epoch, and one or more
mal by assessing whether the EEG patterns are appropriate for matura- of the following EEG patterns appear: 1) a diffuse lower voltage mixed
tional age. Sleep in infants at term can be scored as NREM and REM frequency activity; 2) hypnagogic hypersynchrony; 3) rhythmic anteri-
sleep because all the polysomnographic and EEG features of REM sleep or theta of drowsiness; 4) diffuse high voltage occipital delta slowing;
are present and quiet sleep, if not NREM sleep, is at least “not REM 5) runs or bursts of diffuse, frontal, frontocentral, or occipital maximal
sleep.” The dominant posterior rhythm (DPR) of relaxed wakefulness rhythmic 3-5 Hz slowing; 6) vertex sharp waves; and/or 7) post-arousal
increases in frequency with age: 1) 3.5-4.5 Hz in 75% of normal infants hypersynchrony. K complexes first appear 5 months post-term and are
by 3-4 months post-term; 2) 5-6 Hz in most infants 5-6 months post- usually present by 6 months post-term, whereas clearly recognizable
term; 3) 6 Hz in 70% of normal children by 2 months of age; and 3) 8 Hz vertex sharp waves are most often seen 16 months post-term. Vertex
(range 7.5-9.5 Hz) in 82% of normal children age 3 years, 9 Hz in 65% sharp waves are best seen over the central (C, C, C) and K complexes
z 3 4
of 9-year-olds, and 10 Hz in 65% of 15-year-old controls. Sleep spindles over the frontal (F, F, F) electrodes. Slow wave activity (SWA) of slow
z 3 4
in children occur independently at two different frequencies and two dif- wave sleep (SWS) is first seen as early as 2 to 3 months post-term and
ferent scalp locations: 11.0-12.75 Hz over the frontal and 13.0-14.75 Hz is usually present 4 to 4.5 months post-term. SWA of SWS in an infant
over the centroparietal electrodes; these findings are most prominent in or child often has a peak-to-peak amplitude of 100 to 400 μV. Based
children younger than 13 years. Centroparietal spikes are often maximal on consensus voting we recommended scoring N1, N2, and N3 cor-
over the vertex (C), less often maximal over the left central (C) or right responding to NREM 1, 2, and SWS whenever it was recognizable in
z 3
an infant’s PSG, usually by 4 to 4.5 months post-term (as early as 2-3
months post-term). Epochs of NREM sleep which contain no sleep spin-
Disclosure Statement dles, K complexes, or SWA would be scored as N1; those which contain
This is was not an industry supported study. Dr. Grigg-Damberger has fi- either K complexes or sleep spindles and <20% SWS as N2, and those
nancial interests in GlaxoSmithKline and Sanofi-Aventis. Dr. Gozal is on the in which >20% of the 30-second epoch contain 0.5 to 2 Hz >75 μV (usu-
speakers bureau for Merck. Dr. Marcus has received research support and ally 100-400 μV) activity as N3. The DPR should be scored in the EEG
use of equipment from Respironics. Dr. Quan has participated in speaking channel that is best observed, (typically occipital), but DPR reactive to
engagements for Takeda and has received research support and/or use of eye opening can be seen in central electrodes. Because sleep spindles
equipment from Respironics. Dr. Rosen has received research support from occur independently over the frontal and central regions in children, they
Cephalon. Dr. Chervin is on the scientific advisory board of Pavad Medical should be scored whether they occur in the frontal or central regions.
and is a consultant for Alexa Pharmaceuticals. Drs. Wise, Picchietti, Shel- Because sleep spindles are asynchronous before age 2 years, simul-
don, and Iber have indicated no financial conflicts of interest.
taneous recording of left and right frontal and central activity may be
warranted in children 1-2 years of age. Simultaneous recording of left,
Submitted for publication February 1, 2007
right, and midline central electrodes may be appropriate because of the
Accepted for publication March 15, 2007
asynchronous nature of sleep spindles before age 2 years, but reliability
Address correspondence to: Madeleine M. Grigg-Damberger, M.D., Uni-
testing is needed. Evidence has shown that the PSG cannot reliably be
versity of New Mexico School of Medicine, Department of Neurology, 915
used to identify neurological deficits or to predict behavior or outcome in
Camino de Salud, NE, ACC-2, Albuquerque, NM 87131-0001, Tel: (505)
infants because of significant diversity of results, even in normal infants.
272-3342; Fax: [phone]; E-mail: [email protected]
Journal of Clinical Sleep Medicine, Vol. 3, No. 2, 2007 201
M Grigg-Damberger, D Gozal, CL Marcus et al
Normal sleep EEG patterns and architecture are present in the first year better inform clinicians and families exactly what meaning a PSG has in
of life, even in infants with severe neurological compromise. Increasing evaluating a child’s suspected sleep disorder.
evidence suggests that sleep and its disorders play critical roles in the Keywords: Children, EEG, infants, REM, NREM, pediatric, PSG, scor-
development of healthy children and healthy adults thereafter. Reliabil- ing, sleep, visual.
ity studies comparing head-to-head different scoring criteria, recording Citation: Grigg-Damberger M; Gozal D; Marcus CL et al. The visual
techniques, and derivations are needed so that future scoring recom- scoring of sleep and arousal in infants and children: development of
mendations can be based on evidence rather than consensus opinion. polygraphic features, reliability, validity, and alternative methods. J Clin
We need research comparing clinical outcomes with PSG measures to Sleep Med 2007:3(2);201-240
1.0 HISTORICAL PERSPECTIVE ee et al described how EEG patterns in premature infants evolved
with age.13 In 1968, Parmelee et al provided a detailed catalog
Age is probably the single most crucial factor that determines of EEG frequencies, amplitudes, and patterns demonstrating how
how humans sleep. Infants spend half their time sleeping, the characteristic EEG patterns of sleep change in premature in-
adults only about one-third. Age and level of vigilance also in- fants with increasing conceptional age (CA).13 Using this catalog,
fluence the electroencephalogram (EEG) and the polysomnogram they were able to predict an infant’s CA within 2 weeks in 85%
(PSG). Development, maturation, and involution characterize the of infant EEGs scored blindly.13 These early EEG masters applied
curve of our lives, and our sleep patterns change accordingly. power spectra analysis to confirm the validity of their visual in-
Aserinsky (as a graduate student at the University of Chicago) terpretations.12
was first assigned by his advisor, Kleitman, to study sleep not in They found that quiet sleep in infants by the time they reach
adults, but infants. At that time, experimental studies of sleep in term is characterized by one of two EEG patterns: tracé alter-
infants were based solely on behavioral observations.1,2 Between nant or high voltage slow (HVS) activity. Tracé alternant is an
1949 and 1952, Aserinsky sat watching about two dozen infants EEG pattern in which 3-8 second bursts of moderate to high
sleep, studying whether eye movements in infants correlated with voltage 0.5-3.0 Hz slow waves intermixed with 2-4 Hz sharply
sleep depth. He found that sleeping infants exhibited a recurring contoured waveforms alternate with 4- to 8-second intervals of
“motility cycle manifested by ocular and gross bodily activity.”3 attenuated mixed frequency EEG activity; because this pattern
These observations prompted study of whether these changes alternates between activity and much less activity it is considered
also occurred in adults. Kleitman then encouraged Aserinsky to to be “discontinuous.”12 In contrast, HVS consists of continuous
learn Jacobson’s technique for recording eye movements in hu- moderately rhythmic 50-150 μV 0.5-4 Hz slow activity, without
man subjects while awake.4 Aserinsky and Kleitman then used the bursting activity of tracé alternant. HVS represents the more
this approach for recording eye movements (electro-oculogra- mature pattern of quiet sleep in infants. Two EEG patterns are ob-
phy, [EOG]) and coupled it with EEG to record a “two-channel served in active sleep in infants at term: a continuous EEG pattern
polygraph” which confirmed that rapid eye movements occurred called activité moyenne which consists of either low voltage (<50
in regular recurring cycles across the night during sleep, and μV) 5-6 Hz activity or a mixture of high and low voltage activity
that these movements were accompanied by increased peaks of including delta activity called mixed (M).9,16-18
gross bodily activity, a low voltage mixed frequency EEG, and Credit for applying a developmental perspective to the study of
more rapid respiration.5 Further investigation led to the landmark sleep in humans belongs to Roffwarg, Muzio, and Dement who
1957 paper of Dement and Kleitman, in which they coined the published their classic description of sleep state ontogenesis in
term, “REM sleep,” identifying it by the presence of rapid eye Science in 1966.19,20 As a psychiatrist, Roffwarg, was interested
movements and low voltage fast EEG activity and observing in the relationship between dreaming and REM sleep physiol-
that NREM and REM sleep alternated cyclically across a night ogy.20 Anders reported that Roffwarg initially presumed neonates
of sleep.6 All of these seminal discoveries began by watching in- would not have REM sleep because they did not dream.20 Instead,
fants sleep. Aserinsky said that when he presented his work on the Roffwarg and colleagues found infants spend half of their total
study of sleep in infants as part of his doctoral thesis defense, his sleep time in REM sleep, double that of young adults; findings
examiners told him that doctorates are awarded not for obtained which prompted them to theorize that REM sleep must play an
findings but in hope of future results.7 How fortunate for those of important role in fostering development and maturation of the im-
us who practice sleep medicine this proved true. mature brain.
Beginning in late 1950s, Dreyfus-Brisac and Monod8-10 and In 1969, the Association of the Psychophysiological Study of
Parmalee et al11-13 began to study and report the distinctive EEG Sleep (APSS) chartered an ad hoc committee to develop a guide
patterns of sleep in infants. These investigators found that normal for scoring sleep in infants because the sleep scoring criteria
post-term infants demonstrated 2 distinctive sleep states which published by Rechtschaffen and Kales21 were “applicable only
they called “active” sleep and “quiet” sleep: quiet sleep (QS) is to the adult” and had “not taken into account the unique features
characterized by preserved chin EMG, few body movements, of the developing infant.”22 This committee chaired by Anders,
regular respiration and heart rate, and no eye movements; active Emde, and Parmelee, was composed of investigators with “con-
sleep (AS) is characterized by rapid eye movements, frequent siderable expertise in infant sleep research.” Under the auspices
small face and limb movements, irregular respiration and heart of the UCLA Brain Information Service, they met several times
rate, and the absence of or minimal chin EMG activity. These ob- in 1969-1970, and developed consensus-derived terminology,
servations remain valid today. scoring criteria, and a manual containing illustrative examples
By the late 1960s, the distinctive EEG patterns of sleep in neo- for scoring sleep in normal newborn term infants. A Manual for
nates and infants were delineated: Dreyfus-Brisac14,15 and Parmel- Standardized Terminology, Techniques, and Criteria for Scoring
Journal of Clinical Sleep Medicine, Vol. 3, No. 2, 2007 202
Sleep scoring in infants and children
of States of Sleep and Wakefulness in Newborn Infants, first 2.0 METHODS
published in 1971,22 was designed to increase “comparability
of research results.” Like the Rechtschaffen and Kales scoring In November 2005, the Pediatric Task Force recommended a
manual, it was not intended for clinical purposes. The authors separate pediatric review paper on visual scoring of sleep and
hoped it would “be complemented in the future by manuals deal- arousals in infants and children; the Scoring Manual Steering
ing with premature and older infants.” Committee agreed with this recommendation. For the purpose of
Since the 1971 publication of what this paper calls the An- this review, the Pediatric Task Force, like other task forces was
ders manual, several criteria for scoring sleep in infants and/or to: 1) use an evidence-based medicine process for identifying and
children have been published, but none have been widely ac- grading evidence; 2) produce tables following methods used by
cepted or used. Guilleminault and Souquet23 first published in the American Academy of Sleep Medicine (AASM) Standards of
1979 their criteria for scoring sleep in infants between 6 weeks Practice Committee; 3) develop a referenced evidence review pa-
and 12 months of age because they thought the Anders manual per that would serve as annotated supporting text for the manual
overlooked “much information contained in the EEG of older recommendations; and 4) provide a ranked list of considerations
infants.” They reported they had used these rules to score sleep to the steering committee for developing scoring rules.
in over 400 nocturnal or 24-hour PSGs. Hoppenbrouwers re- The Pediatric Task Force did a systematic and comprehensive
ported in 1987 that she and her colleagues at the University of evidence-based review of the medical literature. In order to review
California in Los Angeles had used their sleep scoring crite- relevant literature amenable to evidence-based analysis, the Pedi-
ria in over 400 overnight-PSG studies in infants between birth atric Task Force first formulated the following questions regarding
and 6 months of age.24 Crowell et al (1997) published a set of analysis and scoring of sleep and wakefulness in neonates, infants,
sleep, arousal, and respiratory scoring criteria which they used and children. The questions we formulated are shown in Table 1.
to score PSG recorded at home in 415 infants (35 to 64 weeks With these questions in mind, we performed our first com-
conceptional age) as part of a multi-center prospective study.25 puter-based Medline literature search using the PubMed search
In 1999, Scholle and Schäfer26 published guidelines developed engine on November 29, 2005 using the following key words:
by the Pediatric Task Force of the German Sleep Research Soci- REM sleep, stage 4 sleep, stage 3 sleep, stage 2 sleep, stage 1
ety, which they reported represented an age-appropriate adapta- sleep, sleep onset, alpha AND sleep, delta AND sleep, drowsiness
tion of Rechtschaffen and Kales.21 AND normal, eye blinks, eye movements AND sleep, K complex,
Despite this rich legacy of scientific endeavor, those who spindles, sleep staging, arousal, sleep disruption. We restricted
study sleep in children still have no universally accepted cri- the search to child (0 to 18 years) and all human studies pub-
teria for scoring sleep in pediatric populations. Most clinicians lished in English between 1995 and 2005 year-to-date. The first
use Rechtschaffen and Kales rules, which were never developed search yielded 1,658 citations. A second search covering the time
for pediatric subjects. In 2004, the Board of Directors of the period of 1966 to 2004, done on December 27,2005, identified
American Academy of Sleep Medicine (AASM) decided that a 160 additional citations. These two searches found 1,818 articles;
new sleep scoring manual was needed.27 They hoped the new of these, 242 were deemed relevant to this topic after review of
manual would be based on digital PSG recording techniques, the title and the abstracts. Additional topic-focused searches were
incorporate the effects of age and pathology, and address not performed. The most recent on August 16, 2006, using a process
only visual sleep stage scoring, but also scoring rules for arous- known as “pearling” in which additional articles were identified
als, movements, and respiratory and cardiac events during sleep. from the bibliographies of the articles previously cited and the
Six task forces were organized, one of which was devoted to articles we used to write this paper. We reviewed all abstracts rel-
pediatric issues. evant to pediatric sleep scoring or arousal reliability and valid-
The Pediatric Task Force (see page 233) initially acted as a ity. We assessed reliability by evaluating test-retest reliability and
liaison to other task forces, assisting them in addressing issues inter- and intrascorer reliability. Validity evidence was evaluated
unique to pediatric populations. We reviewed position papers, by identifying physiological correlates, outcome effects, and/or
participated in consensus voting, and assisted in the develop- comparison to a standard. Ultimately, a total of 344 references
ment of rules by the other task forces. We helped develop spe- were used as evidence and as a basis to write this review.
cific pediatric rules for respiratory and cardiac events which are In general, included papers had to present evidence relevant to
summarized in the respiratory and cardiac review papers. As we the scoring of sleep and arousals in infants and children. Exclu-
reviewed the adult visual sleep stage scoring and arousal scor- sion criteria included abstracts, case studies, editorials, reviews,
ing papers, it became apparent to the Pediatric Task Force and and theoretical papers. However, when relevant, we considered
the Scoring Manual Steering Committee that it was important to and sometimes used the latter types of citations as background
write specific rules and terminology for visual scoring of sleep information to help write the general introduction and discus-
in infants and children. Although in the end, the Pediatric Task sion sections of this review paper. The Pediatric Task Force then
Force provided no different rules for scoring arousals in infants prepared evidence tables which helped the Pediatric Task Force
and children than those recommended for adults, we performed and Scoring Manual Steering Committee to develop terminology,
an evidence-based review of this material, discussed it at length, rules, standards, guidelines, and recommendations for scoring
and cite it here to explain the decisions we eventually reached sleep and arousals in infants and children. Evidence tables for this
regarding scoring arousals in infants and children. This review paper will be placed on the AASM website (which can be ac-
paper summarizes the evidence used to support the terminology cessed on the web at www.aasmnet.org). We graded the evidence
and rules contained in the new scoring manual for visual scoring using a classification approach used by the AASM Standards of
of sleep and arousals in infants and children. Practice Committee (Table 2), which is a modification of the clas-
sification system developed by Sackett.28
Journal of Clinical Sleep Medicine, Vol. 3, No. 2, 2007 203
M Grigg-Damberger, D Gozal, CL Marcus et al
Table 1—Questions formulated by the Pediatric Task Force: analyz- Table 2—Evidence classification used by the Pediatric Task Force
ing and scoring sleep/wakefulness in infants, children, and adoles-
cents Evidence Study Design
Levels
1. How should we define the following: neonate, preterm, full term,
1 Randomized well-designed trials with low-alpha & low-
infant, conceptional age (CA), and child?
beta errors
2. Are there existing criteria for scoring sleep in infants and chil-
2 Randomized trials with high-beta errors
dren?
3 Nonrandomized controlled or concurrent cohort studies
3. Are active sleep and quiet sleep immature forms of REM and
NREM sleep, respectively? which study a reasonably well defined sample of adequate
4. At what age following term birth are sleep spindles usually pres- sample size, using standardized techniques
ent? 4 Nonrandomized uncontrolled historical cohort or obser-
5. Are there features of sleep spindles that evolve by age in infants, vational studies
children, and adolescents ? 5 Case reports, case series, or observational studies not ful-
6. At what age following term birth are K complexes and vertex filling the criteria of Level 4
sharp waves usually present?
7. At what age does slow wave activity (SWA) of slow wave sleep
Pediatric Task Force researched, wrote, and submitted portions of
(SWS) appear in normal infants following term birth?
the review paper. A subgroup of the task force (listed as authors)
8. After what age following term birth can we identify and score
NREM sleep as stages 1, 2, and SWS? reviewed and edited this work and wrote this review paper.
9. How does the dominant posterior rhythm (DPR) of relaxed All members of the Pediatric Task Force* were directors or
wakefulness develop and change with age in infants, children, members of sleep disorders centers which either exclusively, usu-
and adolescents?
ally, or often record sleep in infants and children. All members
10. How does the waking EEG background change with age in in-
of the Task Force and the steering committee completed detailed
fants, children, and adolescents?
11. Are there distinctive paroxysmal EEG patterns seen in pediatric conflict-of-interest statements, none of whom reported inherent
subjects in the transition between wake/sleep and stage 1 NREM conflicts of interest related to this subject. The Pediatric Task
sleep? Force met by telephone conference call 10 times between June
12. How does the waking EEG background change with age in in-
21, 2004, and April 9, 2006, for evidence review and RAND/
fants, children, and adolescents?
UCLA consensus voting.
13. What are the characteristic EEG backgrounds of drowsiness and
stage 1 NREM sleep (stage N1) in infants and children?
14. Are there distinctive paroxysmal EEG patterns seen in pediatric 3.0 THE VISUAL SCORING OF SLEEP AND AROUSAL IN INFANTS
subjects in the transition between wake/sleep and stage 1 NREM AND CHILDREN
sleep?
15. What is known about the ontogeny of the development of the 3.1 Definitions of age, term, and conceptional age in infants and
non-EEG physiological measures of REM sleep (rapid eye children
movements, chin EMG and limb atonia, irregular respiration,
phasic muscle twitches, and gross body movements in infants?
Normalcy of an infant’s EEG or PSG can only be determined
How can we use these to identify REM sleep in infants?
by assessing whether the EEG patterns are appropriate for matu-
16. What is the evidence for the reliability of recording and scoring
sleep in in-laboratory polysomnograms in infants and children? rational age.30 Normalcy of an infant EEG is determined not by
17. What are the indications for polysomnography in infants, chil- chronological age (number of days or weeks following birth) but
dren, and adolescents? by conceptional age (CA). The American Academy of Pediatrics
18. What is the evidence for the validity of scoring sleep in infants
(AAP) published in 2004 recommendations for age terminology
and children?
to more accurately define length of gestation and age in neonates,
19. Until what age following term birth should we use the Anders
infant sleep scoring criteria? infants and children.31 The AAP recommends that gestational age
20. Which epoch length should be used to score sleep in infants and (GA) be defined as the time elapsed in completed weeks between
is there compelling evidence that the scoring interval should be the first day of the last normal menstrual period and the day of
different than adults?
delivery. A fetus with a GA of 25 weeks, 5 days is still considered
21. Over which EEG electrodes are dominant posterior rhythm,
a 25-week fetus; rounding the GA up to 26 weeks is regarded as
sleep spindles (SS), K complexes (KC), slow wave activity
(SWA), sawtooth waves best seen in pediatric subjects? Is the inconsistent with national and international norms.32 If the preg-
scalp topography of these distinctive polysomnographic features nancy was achieved using assisted reproductive technology, GA
different in infants, children, or adolescents, compared with is calculated by adding 2 weeks to the CA. Chronological age is
adults?
the time in days, weeks, months, or years from birth.
22. Are significant first night effects observed when recording a
The AAP policy statement recommends abandonment of the
single night of in-laboratory PSG in a child?
23. What technical considerations are appropriate when recording term “conceptional age” because of its many inherent inaccura-
PSG in pediatric subjects? Are any of these different from those cies.33 However, conceptional age (CA) must be defined for this
recommended for adults? paper because much of the evidence we present defines age-ap-
propriate EEG patterns in neonates and infants in relation to con-
When insufficient evidence was available for specific items, the
ceptional age. CA is calculated by adding the estimated gesta-
Pediatric Task Force used the UCLA/Appropriateness Method29 to
tional age to the chronological age.
develop consensus agreement. We submitted our evidence review
The AAP policy now recommends we use the following ter-
and consensus balloting of the Pediatric Task Force to the steering
minology: 1) When a neonate is still in the hospital following
committee who, with the Pediatric Task Force chair, crafted the
birth, “postmenstrual age” is the preferred term defined by the
final scoring rules, standards, guidelines, consensus recommen-
gestational age plus the chronological age in weeks; 2) After this
dations, and technical specifications. Different members of the
Journal of Clinical Sleep Medicine, Vol. 3, No. 2, 2007 204
Sleep scoring in infants and children
perinatal period, “corrected age” is the preferred term, defined as
the chronological age in weeks or months reduced by the number Concept of Surface-Negative and Surface-
of weeks born before 40 weeks of gestation. Corrected age should Positive Deflection in EEG and PSG
be used only for children born prematurely and only until 3 years Negative deflection
of age. In future studies, we recommend reporting data using this of a K-complex
new age-related terminology.
By convention, prematurity is conceptional age less than 38
wks, and full term is 38 to 42 weeks CA. A neonate is a child
during the first 28 days after birth. An infant is a child age 1 to 12
months of age. A child is someone younger than 18 years of age.
From a physiological standpoint, an adolescent is probably best
defined using Tanner sexual maturity staging.34 Positive deflection
The importance of defining an infant’s conceptional age arises of a K-complex
because the EEG (or a PSG) of a normal infant is more dependent
Figure 1—Concept of surface-negative and surface-positive de-
upon the age of the brain following conception than the number
flection in EEG and PSG. By convention, upward pen (or digital)
of days following birth.35,36 Except when stressed, or in situations deflections mean a net negative potential difference between two
involving encephalopathy or medication-related factors, the EEG electrodes; a downward deflection means a positive electrical dif-
or PSG of a neonate reflects the actual developmental age of the ference between two electrodes. A biphasic K complex waveform
brain.37 The brain, EEG, and PSG of an infant continue to develop has two phases, an initial upward “negative” deflection followed by
and mature at a similar rate, independent of whether the infant a positive “downward” deflection. Sometimes, the waveform which
is predominantly upward is described as “surface negative” and
is in utero or post-delivery. An EEG or PSG of a normal prema-
downward as “surface positive” because much of the EEG is a radial
ture infant born at 32 weeks gestational age whose chronologi-
electrical dipole.
cal age is 8 weeks should resemble that of a normal infant born
at 40 weeks gestational age two days earlier. The EEG and PSG
2 electrodes (e.g., F-C which links the midline frontal [F] to the
patterns observed in infants 6 months or younger correlate most z z z
midline central [C] electrode).
closely with the infant’s CA; after that the number of months in z
By convention, upward pen (or digital screen) deflections
age post-term birth usually suffices.
indicate a negative potential difference between 2 electrodes; a
downward deflection indicates a positive electrical difference be-
3.2 Definitions of electroencephalography crucial to understanding
tween the 2 electrodes. For example (Figure 1), a K complex is
arguments in this review
a biphasic wave (i.e., the “complex” crosses the EEG baseline
The frequency range for scalp-derived EEG in humans lies be- twice, once up (negative) then down (positive). Sometimes, we
tween 0.3 to 70 Hz (cycles per second).38 By convention, normal call the waveform which is predominantly upward “surface nega-
EEG background is divided into 4 main frequency bands: delta tive” and downward “surface positive” because most of the nor-
(0.5 to <4 Hz); theta (4 to <8 Hz); alpha (8 to 13 Hz); and beta mal background EEG is a radial electrical dipole.
(>13 Hz).39 Most EEG laboratories use the International 10/20
system to place electrodes in standardized scalp locations. This 3.3. Earlier criteria for scoring sleep and wakefulness in pediatric
system places electrodes at 10 and 20 percent deviations from subjects
four anatomical landmarks (the nasal bridge (nasion), the inion
3.3.1 The Anders manual for scoring sleep/wake states in full-term
(occipital proturberance), and the right and the left preauricular
newborns
points (depression in front of each ear). Electrodes are named by
their location (e.g., F, C, O for frontal, central, and occipital, re-
The Anders manual defined sleep scoring criteria and termi-
spectively); those on the left side of the head are given odd num-
nology only for normal full-term newborns. It differs from the
bers; those on the right are even; and the midline derivations are
Rechtschaffen and Kales manual in that it provides a system for
denoted with “z.” Electrode names of particular interest to those
coding only sleep/wake states (and their behavioral correlates),
involved with PSG are: frontal (F, F), central (C, C), occipital
3 4 3 4 leaving “specific criteria for scoring states… to the investiga-
(O, O), and midline (F, C, O). These standard deviations and
1 2 z z z tor.”22 The Anders manual provides a system for coding respira-
electrode position names are used in this paper. There are 2 fun-
tion, eye movements, muscle tone, respiration, movements, and
damental methods of representing EEG activity: referential and
vocalizations to distinguish states of sleep and wakefulness. Like
bipolar derivations (also called montages). A referential montage
Rechtschaffen and Kales, the criteria proposed by the Anders
links an “active” electrode placed over a “biologically active” site
manual were consensus-based, reflecting the views, experience,
to a “reference” electrode placed over a relatively inactive site
and medical research available to the authors.
such as the earlobe (A, A) or the mastoid (M, M). The signal
1 2 1 2 Anders and his coauthors classified sleep into 3 states: active
represents a recording of the electropotential difference between
sleep (AS), quiet sleep (QS), and indeterminate sleep (IS); they
the recording site of interest and the reference (comparison) site.
further presumed that QS and AS were, respectively, antecedents
The Rechtschaffen and Kales scoring manual recommended cen-
of NREM and REM sleep.22 The authors recognized and defined
tral EEG derivations (C-A, C-A) for scoring sleep stages; these
3 2 4 1 3 states of wakefulness (“crying,” “active awake,” and “quiet
are referential derivations. 21 A bipolar montage links two biologi-
awake”) and 4 EEG patterns of sleep (tracé alternant and HVS in
cally active electrodes to each other, and the signal represents the
quiet sleep, low voltage irregular (LVI) or M in active sleep) in
net electrical negative or positive potential difference between the
post-term infants. The Anders criteria emphasized that behavioral
Journal of Clinical Sleep Medicine, Vol. 3, No. 2, 2007 205
M Grigg-Damberger, D Gozal, CL Marcus et al
observations were necessary to differentiate between states of sleep EOG, chin EMG, and behavior correlates, using 30-second ep-
and wakefulness in the infant and were critical for accurate interpre- och lengths.23 Their scoring criteria reflect how EEG patterns of
tation of polysomnographic recordings (PSG) in infants.16,19,40 The wakefulness, sleep onset, NREM, and REM sleep change with
minimum behavioral notations needed to interpret each epoch of an age. Sleep onset in infants 3 to <6 months post-term was her-
infant PSG were: 1) eyes open or closed; 2) presence or absence of alded by a high amplitude burst of >100 μV theta activity. Stage
body movements; and 3) crying (when present). The Anders man- 1 NREM sleep in infants 3 to <6 months post-term consisted of
ual recommended scoring an entire sleep record from “Lights Out” a wide range of mixed 1-15 Hz EEG frequencies, if <20% of the
to “Lights On” using either 20-second or 30-second epochs. 30-second epoch contained delta slow waves >150 μV. If sleep
The authors thought the most useful polysomnographic charac- spindles were present, the epoch would be scored as stage 2.
teristic for scoring sleep in infants was the regularity or irregular- Sleep onset in infants 6 to 12 months post-term was heralded
ity of respiration. They defined regularity or irregularity of respi- by a burst of “regular high amplitude theta waves” and stage 1
ration by measuring the variability in respiratory rate between the by mixed (1-12 Hz) EEG frequencies, but with a predominance
longest and shortest respiratory cycle within a 20- or 30-second of 3-7 Hz theta activity. They distinguished stage 1 from stage
epoch, extrapolating these rates for one minute. Regular respira- 2 by the absence of sleep spindles in stage 1 and by <20% SWS
tion was then a period in which the respiratory rate varied <20 (>150 μV <2 Hz delta waves) in the 30-second epoch. Char-
breaths per minute; irregular respiration when it varied by >20 acteristic for stage 2 sleep in infants 6-12 months of age was
breaths per minute.10 Appendix Table 1 (which can be accessed predominant theta activity, 12-14 Hz sleep spindles, and <20%
on the web at www.aasmnet.org) summarizes the EEG and poly- of the epoch with >150 μV <2 Hz delta waves. SWS was scored
somnographic features of active sleep (AS), quiet sleep (QS), and whenever >20% of the 30-second epoch contained >150 μV <2
indeterminate sleep (IS) of the Anders manual.22 Hz delta waves.
Their criteria characterized the EEG background of REM sleep
3.3.2 Hoppenbrouwers sleep scoring criteria for infants, birth to 6 in infants 3 to 12 months post-term as “a predominance of theta”
months activity, again emphasizing the importance of relying upon behav-
ioral correlates (EOG, chin EMG, movement) to identify REM
Hoppenbrouwers sleep scoring criteria were developed to score sleep in infants. The authors recommended continuing to score
sleep in infants from birth to 6 months post-term.24 Similar crite- epochs as stage 2 unless the spindle-to-spindle interval was lon-
ria in the Anders manual, there were 4 recognized 4 sleep/wake ger than 5 minutes (versus the “3-minute rule” of Rechtschaffen
states: awake (AW), active sleep (AS), quiet sleep (QS), and in- and Kales). Appendix Table 2 (which can be accessed on the web
determinate sleep (IS). The Hoppenbrouwers criteria emphasized at www.aasmnet.org) summarizes the Guilleminault/Souquet cri-
the importance of behavioral correlates, especially regularity or teria for scoring sleep in infants 6 weeks or older.23
irregularity of respiration, in distinguishing AS and QS (particu-
larly when the EEG background is one of the continuous EEG 3.3.4 Crowell infant sleep scoring criteria
patterns). They scored sleep using 60-second epoch lengths.
To score active sleep (AS) in infants from birth to 6 months Crowell et al scored sleep in 415 infants (34 to 64 weeks
post-term using the Hoppenbrouwers criteria requires the absence CA) using criteria they developed for recording PSG at home as
of sustained EMG tonus together with three of the following part of the CHIME study (a prospective multi-center collabora-
criteria: 1) at least one eye movement, independent of chin and tive home infant monitoring study).25 They used C -A as the
4 1
gross body movements; 2) breathing rate variation greater than primary EEG derivation and C -A as a “back-up channel” in
3 2
25 breaths per minute as measured by the respiratory tachome- case the first channel malfunctioned. To score a particular EEG
ter; 3) presence of twitches and brief head movements; and/or 4) pattern, it had to occupy >50% of a 30-second epoch. As oth-
absence of EEG spindles or tracé alternant. Scoring quiet sleep ers had earlier, they recognized two different continuous EEG
(QS) requires all of the following: 1) breathing variation of no patterns during active sleep. They used the same name as oth-
greater than 25 breaths per minute as measured by the respiratory ers had earlier for Mixed which they described as high and low
tachometer; 2) eyes are closed with no more than one isolated voltage waves with little periodicity. However, they called low
eye movement; 3) sustained EMG tonus, EEG spindles, tracé al- voltage mixed frequencies fast, characterized by “low voltage
ternant, or both. To score awake (AW) requires at least three of <35 μV 5-8 Hz theta intermixed at times with 1-5 Hz activity.”
the following criteria be met: 1) Sustained EMG tonus with ac- They recognized and scored three different EEG patterns during
tivity bursts; 2) Eyes open; 3) Within a given minute breathing quiet sleep: high voltage (>50 μV, 0.5 to 4.0 Hz for >50% of the
rate variation greater than 45 breaths per minute as measured by 30-second epoch), Mixed (as defined for active sleep), or trace
the respiratory tachometer; 4) Vocalization; and/or 5) Sustained alternant.
gross movements. Epochs of sleep in infants in which the criteria Tracé alternant was scored when an alternating pattern of 3 or
for AW, AS, and QS are not fulfilled, or minutes in which these more runs of high voltage activity lasting 3 to 8 seconds alternat-
criteria are fulfilled for less than 30 consecutive seconds (state ing with low voltage activity lasting 4 to 12 seconds occurred,
transitions), are scored as indeterminate sleep (IS). cautioning that periodicity needed to be “readily observed” and
allowing scorers to look at the preceding or following 30-second
3.3.3 Guilleminault and Souquet sleep scoring criteria for infants, epochs to find the 3 patterns. They defined regularity or irregular-
3-12 months ity of respiration using Anders criteria and methodology. Criteria
required eye movements to be out-of-phase, similarly shaped, and
Guilleminault and Souquet criteria recommended scoring sleep produce synchronous deflections of at least 30 μV or more in both
and wake in infants 3 to 12 months post-term based upon EEG, EOG channels.
Journal of Clinical Sleep Medicine, Vol. 3, No. 2, 2007 206
Sleep scoring in infants and children
3.3.5 Scholle and Schäfer criteria for scoring sleep in infants and beginning between ages 2 months and 12 months. Finally, they
children characterized the age-related changes in the sleep/wake transition
as: 1) indeterminate between ages 33 to 44 weeks conceptional
The Pediatric Task Force found only one set of criteria de- age; 2) rhythmic theta activity increasing in amplitude compared
vised for scoring sleep in children older than infants. Scholle and to wakefulness was often noted beginning at 6 months of age; 3)
Schäfer published in Somnologie (the official journal of the Ger- Hypnagogic hypersynchrony (rhythmic 4 to 6 Hz theta activity)
man Sleep Research Society) criteria for scoring sleep in infants first observed age 1 year, progressively declines and seldom seen
and children accompanying an atlas, which shows representative after age 12 years.
normal PSGs in infants and children.26 The Pediatric Task Force
of the German Research Society who developed these criteria said 3.3.6 Criteria for scoring sleep in infants based solely upon behav-
they were needed because EEG amplitudes in infants and children ioral observations
during NREM sleep are much higher than in an adults so that the
Rechtschaffen and Kales >75 μV amplitude criterion is not ap- Early studies of scoring or “staging” sleep in infants were
plicable to children. They said these age-appropriate sleep scoring based solely upon behavioral observations.1-2 In 1964, Prechtl
criteria were adapted from Rechtschaffen and Kales.21 and Beintema developed a scale for scoring sleep/wake states in
Significant features of the Scholle/ Schäfer criteria include: 1) infants based solely on observable behaviors.345 They classified
noting the dominant posterior “alpha” rhythm of relaxed wakeful- sleep/wake in infants 36 to 44 weeks CA into 5 different stages
ness increases in frequency with increasing age; 2) the EEG pat- based upon behavioral features: 1) eyes closed, regular respira-
terns of stage 1 NREM sleep include either vertex sharp waves, tion, no movements; 2) eyes closed, irregular respiration, no gross
low voltage theta and delta activity, or hypnagogic waves; 3) the movements; 3) eyes open, no gross movements; 4) eyes open,
high voltage of slow wave activity to score slow wave sleep is gross movements, no crying; 5) eyes open or closed, crying. Even
gauged by comparing it to the mean amplitude of EEG activity after the development of the Anders manual, which combined be-
observed during stage 2 NREM sleep. They provided the follow- havioral and polysomnographic correlates, Anders and many of
ing age-related frequencies for the posterior alpha rhythm in chil- his colleagues continued to study infants using only behavioral
dren: starting at 2 to 4 months, 2-4 Hz; 6-7 Hz at 12 months; 5 to observations.
8 Hz at 1 to 3 years; 6-8 to 7-9 Hz at 3 to 5 years; 8-10 to 9-11 Hz One such behavioral scoring criteria used by Anders and Chale-
at 5 to 12 years; and 10 Hz (8.5-13 Hz) >12 years. mian270 classified wakefulness into 4 different states: 1) Fussy-
The Scholle and Schäfer criteria also reported that EMG mus- Cry (FC) characterized by the presence of vigorous diffuse motor
cle tone was high during wakefulness, progressively decreased activity and varying intensities of vocalization; 2) Wakeful Activ-
with deepening NREM sleep reaching its lowest level during ity (WA) with frequent spurts of diffuse motor activity, open eyes,
REM sleep. EOG during wakefulness included eye blinks and and occasional grunts; 3) Alert Inactivity (AI) with occasional
rapid eye movements, slow eye movements during NREM 1, and directed motor actions and wide open eyes that pursued targets;
rapid eye movements during REM sleep. Sleep spindles need to and 4) Drowsy (DR) with relative immobility, absence of focused
last 0.5 seconds or more to score them as a feature of NREM 2. attention, and opening and closing of eyes. Quiet sleep (QS) was
Sleep spindles and broad K complexes may be seen in NREM 3; identified by regular respiration and the absence of eye and body
sleep spindles are observed sometimes even in NREM 4. NREM movements except for an occasional nonnutritive sucking and ac-
3 sleep was identified by high voltage delta waves occupying tive/REM (AR) sleep when rapid eye movements, facial grimac-
20% to 50% of an epoch, and greater than 50% of epoch charac- ing, writhing body movements, irregular respiration, and isolated
terized NREM 4 sleep. Of note, they recommended identifying limb twitches were observed.
“high voltage” slow wave sleep in children by the delta waves
higher than the mean amplitude of NREM 2 sleep. 3.4 Are quiet sleep and active sleep immature forms of NREM and
Finally, the Scholle and Schäfer sleep scoring criteria26 identi- REM sleep, respectively?
fied typical EEG patterns seen during sleep and noted how these
The authors of the Anders manual presumed that quiet sleep
changes with maturation which they modified from Niedermeyer
and active sleep were immature forms of NREM and REM sleep,
and Lopes da Silva.41 Scholle and Schafer criteria specify that:
respectively. Conflicting evidence and opinions on this issue are
1) 12-15 Hz “pre-spindles” may be seen before 10 weeks of age
justified in part by findings in neonatal animal models whose
and note that immature sleep spindles are often rounded negative
maturational state is equivalent to that of very immature infants.
and have a sharp positive component; 2) progressive increases of
Gramsbergen42 and Frank and Heller43 argue that sleep in infant
inter-spindle intervals occur with increasing age; 3) from 18 to 24
rats younger than 12 days of age represents a primitive undif-
months, mature sleep spindles without a rounded component are
ferentiated behavioral state—an amalgam of sleep components,
observed; 4) anterior 12 Hz and central 14 Hz sleep spindles are
which gradually differentiate into REM and NREM sleep later in
seen from age 2 years on; and 5) 14 Hz sleep spindles maximal
development. They further argued that AS was best considered as
at the vertex (Cz) with independent 12 Hz sleep spindles over the
an undifferentiated behavioral state (which they called presleep)
anterior regions after 3 years of age. High amplitude K complexes
from which both SWS and REM sleep eventually emerge.
are first seen at 5 months of age, fully developed by age 2 years;
Other investigators have argued that the development of sleep
vertex sharp waves are first seen at 8 weeks of age and are most
in mammals represents a continuous elaboration of the compo-
prominent between ages 3 to 10 years. So-called REM storms, are
nents that are already in place and identifiable in early infancy.44-46
rapid eye movement burst patterns, first seen after 28 weeks con-
Recently, Karlsson et al47 demonstrated that all the neuronal con-
ceptional age and maximal at 33 to 36 weeks; rapid eye movement
nections which generate muscle atonia and myoclonic twitching
inter-burst intervals typically declined to less than one per second
Journal of Clinical Sleep Medicine, Vol. 3, No. 2, 2007 207
M Grigg-Damberger, D Gozal, CL Marcus et al
during AS are already well established in neonatal rats equiva- proximately 34 weeks CA. By 36 weeks CA, all the EEG and
lent in developmental age to human infants 32 weeks CA. This behavioral correlates of wakefulness, active sleep, and quiet sleep
prompted the argument that if all the REM sleep generator mecha- are clearly recognizable, although large percentages of sleep are
nisms and connections are present in infant rats at birth and are still best scored as indeterminate sleep. Indeterminate sleep repre-
similar to those seen in adult cats, then it is likely that AS in in- sents “discordant” sleep where mixtures of > 2 sleep/wake states
fants by 32 weeks CA is simply an immature form of REM sleep are seen within a given epoch. The percentage of indeterminate
seen in older children and adults. sleep falls rapidly after 36 weeks CA. Regular heart rate and res-
Although it seems intuitive, we actually have no evidence that piration, elevated chin EMG tone, and absence of eye movements
QS is an immature form of slow wave sleep. Some have suggest are observed in epochs of well-differentiated QS in infants at 40
that quiet sleep before the appearance of sleep spindles, K com- weeks CA.16,52,53 Normal infants at 40 weeks CA exhibit a sizeable
plexes, or SWA is an undifferentiated sleep state and simply “not repertoire of motor behaviors: sucking movements, fine muscle
AS/REM sleep.” Whether the high voltage 0.75 to 1.75 Hz ac- twitches, chin, body and limb tremors, grimaces, smiles, intermit-
tivity which emerges as early as 2 months post-term represents tent stretching, and large athetoid limb movements.54,55
EEG activity generated by the same neuronal generators and con- Early infant sleep researchers found many epochs of sleep are
nections as SWA seen at a later developmental age is controver- best scored as “indeterminate sleep” as late as 3 months post-term.
sial.48,49 More research and evidence is needed. Coons and Guilleminault scored 33% ± 7% of total sleep time as
indeterminate sleep in 10 normal infants at age 3 weeks post-term,
Summary: Are active and quiet sleep immature forms of REM and 32% ± 7% at 6 weeks.56 Parmalee et al reported that 67% of total
NREM sleep, respectively? sleep time was IS in an infant 30 weeks CA, 38% at 40 weeks CA,
and falls to 29% 3 months post-term,57 still a sizeable percentage
The Pediatric Task Force discussed whether to continue using of the total sleep time. Anders and Sostek found they were able to
the traditional terms quiet sleep (QS) and active sleep (AS) when significantly reduce the amount of indeterminate sleep they scored
scoring infants, especially those younger than 3 months post-term. in a PSG by permitting scoring of AS, QS, or AW if <2 polysom-
The Pediatric Task Force used the following reasoning to recom- nographic correlates were discordant for the sleep state.58 DeWeerd
mend that sleep in infants ≥2 months post-term should be scored and van den Bossche emphasize in their excellent review of the
as NREM and REM sleep: 1) all the EEG and polysomnographic development of sleep during the first months of life that state of a
features of REM sleep are present by this age; 2) convenience and child at one particular moment can only be assessed approximately
simplicity; and, 3) quiet sleep, if not NREM sleep by this age, is 50% to 80% of the time, and the remaining periods are indeter-
at least “not REM sleep.” minate.59 They caution that while it is desirable to have a global
idea of which state an infant is in at particular recording time, a
3.5 Development of the non-EEG polysomnographic features of
procrustean approach if taken too often, leads to forced and often
REM and NREM sleep in infants meaningless scoring of sleep/wake states in a young infant’s PSG.
Indeterminate sleep in infants is particularly challenging when try-
Readers less experienced in scoring sleep in young infants may
ing to train an automatic computer scoring system.
at first be puzzled by the inclusion of this topic so early in the
position paper. Under normal circumstances, REM sleep and its
3.5.2 Ontogeny of rapid eye movements
behavioral correlates would be appropriate for discussion after
those of wakefulness and NREM sleep. However, sleep onset is Rapid eye movements (REMs) are first seen as early as 31
typically REM sleep in infants <3 months post-term, and REM weeks CA or even earlier.17,60-62 Parmelee et al (1969, 1972) re-
sleep constitutes about 50% of the total sleep time (TST) in term ported that eye movements occurred almost “continuously” in
infants. Finally, differentiating quiet sleep and active sleep can- infants at 28 to 30 weeks CA but then only at a rate of 1 to 4 per
not be done based solely on EEG when an infant’s sleep EEG is minute.11,52 However, by 32 weeks CA, REMs when seen often
a continuous pattern of HVS (seen in QS at term) or mixed (seen occur in clusters: 1 to 6 eye movements per minute in 37% of 20-
in the first cycle of AS in term infants). Because active and quiet second epochs, ≥9 per minute in 13% of epochs.
sleep cannot be differentiated in neonates and young infants solely Premature infants will often display increased REM density.
based upon the EEG, the behavioral correlates (i.e., the non-EEG Clusters of intense REMs in premature infants have been called
physiological correlates) of REM (and NREM) sleep are needed “REM storms.”63 Kohyama et al used PSG to study REM densi-
to differentiate QS from AS.22,50 ties in 32 normal infants 33 to 184 weeks CA, finding that REM
densities were highest in infants 36 to 38 weeks CA.64 Becker and
3.5.1 EEG and behavioral correlates of active and quiet sleep clearly
Thoman studied REM densities in PSGs of 15 normal infants 2
recognized by 36 weeks conceptional age to 5 weeks of age and again at 3, 6, and 12 months. They found
that REM storms markedly decreased after 40 weeks CA. Their
Sleep is undifferentiated in human infants before 32 weeks CA.
data suggested that the continued presence of REM storms after
By approximately 32 weeks CA, active sleep and quiet sleep can
6 months of age could indicate developmental delay or dysfunc-
be distinguished by their behavioral correlates, but not by the still-
tion.11,63 Of note, the Scholle/Schäfer criteria call the increased
undifferentiated EEG activity.17,51 At approximately 32 weeks CA,
REM density of preterm infants the “burst pattern” of rapid eye
rapid eye movements and phasic muscle twitches identify AS,
movements, say it is characterized by “high density bursts with
and QS is associated with the presence of far fewer movements
inter-burst intervals of less than one second,” first seen after 28
(except for an occasional myoclonic jerk and some buccolingual
weeks, is maximal 33 to 36 weeks CA, and decreases across the
movements).17
first year of life.26
Recognizable EEG patterns of AS and QS first appear at ap-
Journal of Clinical Sleep Medicine, Vol. 3, No. 2, 2007 208
Sleep scoring in infants and children
3.5.3 Ontogeny of muscle atonia piration in infants at 3 months of age; and in 91% and 98% at 8
months of age. More recently, Kirjavainen et al found that REM
Chin EMG (a polysomnographic measure of skeletal muscle sleep was best recognized by its distinctive pattern of irregular
atonia) in children and adults is typically absent or markedly re- respiration with superimposed periods of tachypnea and found
duced during REM sleep and present during NREM sleep. The that irregularity of respiration was a particularly useful behavioral
reliability or concordance of chin muscle atonia as a polysom- correlate when they recorded and staged sleep using only a static
nographic characteristic to distinguish REM from NREM sleep charge sensitive bed.75
also develops with age. Concordant elevated chin EMG activity
during quiet sleep is first seen at 34 wks CA, but it transiently be- 3.5.6 Task force summary regarding the value of non-EEG poly-
comes discordant (with the other EEG and behavioral correlates somnographic behavioral correlates to distinguish NREM and REM
of QS) between 37 to 40 wks CA.16,52 However, after 40 weeks CA sleep in infants
the presence of muscle tonus during QS was found to be a usu-
ally “reliable” and valid measure of QS in post-term infants.16,52 After reviewing the literature and clinical experience, the Pe-
While these investigators touted the reliability of the chin EMG diatric Task Force agreed that usually all the basic electrophysi-
in post-term infants, they still found it inappropriately absent ological correlates of active (REM) sleep (decreased or absent
(when it should be present) approximately 15%-20% of QS time. chin EMG tone, rapid eye movements, phasic muscle twitches, ir-
The authors argue such chin EMG reliability values are similar to regular respiration and heart rate, low voltage mixed activity) are
those observed in infants 6 months post-term16,17,52,65,66 and compa- present in full-term infants 40 weeks CA or older. These indica-
rable to values of 20% of NREM sleep in adults.67 Taken together, tors are sufficiently reliable to distinguish NREM and REM sleep
these studies suggest chin EMG will be discordant (absent when in full-term infants 40 weeks CA or older. Still, chin EMG tone
it should be present) during 15%-20% of NREM sleep time from will be absent during quiet sleep in about 15%-20% of quiet sleep
term to adulthood. time which matches percentages reported in infants 6 months of
age, comparable to values of 20% in adults. The Pediatric Task
3.5.4 Infants 3 months or younger move more during sleep than Force supported the concept that behavioral correlates can be
older infants very helpful in scoring NREM and REM sleep, especially in in-
fants younger than 6 months of age.
Young infants move more during sleep than older infants, chil- The Pediatric Task Force thought it would be important to as-
dren, or adults, yet these movements often cause no arousal. It sess the regularity or irregularity of respiration especially when
is important to avoid overscoring movements as arousals in in- scoring quiet/NREM sleep but we did not have sufficient evi-
fants.68 We found a few studies examining how the numbers of dence to make it a stand-alone criterion for staging sleep in pedi-
movements seen during sleep lessen in infants especially after atric subjects. Although earlier studies and investigators tout its
3 months of age. Fukumoto et al studied the age-related ontog- value, we do not have evidence for its reliability in those whose
eny of gross, localized, and phasic (twitches lasting <0.5 second) sleep is fragmented by sleep disordered breathing (SDB), frequent
movement in subjects between age 30 weeks CA to 18 months movement and EEG arousals, and/or contains generous amounts
post-term.69 They found that: 1) all types of body movements de- of indeterminate sleep. Thus, while we note the importance of
crease with increasing age; 2) phasic muscle activity was the first regular respiration during quiet/NREM sleep, it is not mandatory
to decrease, localized body movements next, but the frequency of for scoring this particular stage of sleep.
gross body motor movements during sleep remained unchanged Finally, we agreed that sleeping infants move more and have
until a basal level of 9 to 13 months post-term; and 3) the num- more position shifts during sleep than older subjects, but many of
ber of epochs without body movements increased steadily until these movements and position shifts do not cause arousal. Thus,
about 8 months post-term. Leifting et al found the numbers of assuming movement or position change in an infant signals a cor-
phasic muscle twitches during AS decrease after 3 months in their tical arousal will lead to overscoring of arousals, particularly in
study of quantitative chin EMG activity in a single night of PSG infants <3 months post-term.
recorded on 23 healthy term infants who varied in age from 2 to
47 weeks.70 3.6 Development and characteristic features of sleep spindles in
infants and children
3.5.5 Regularity or irregularity of respiration to distinguish NREM
and REM sleep The next major polysomnographic feature of sleep which de-
velops in the transition from neonatal to infant sleep is the sleep
Many studies report regularity of respiration is reliably present spindle. Sleep spindles were first reported by Berger in 1933,76
in infants by 40 weeks CA.14,16,71-74 Parmalee et al (1972) in their but Loomis et al in 1935 were the first to use the term for 1 to 1.5
study of the maturation of respiration in from 30 weeks CA to 8 second bursts of 20-40 μV, 14-15 Hz activity which waxed and
months post-term, found that: 1) regular respiration was rare at waned in amplitude and occurred during NREM sleep.77
32 weeks CA, but when present was likely to be associated with
absence of eye movements; 2) simultaneous appearance of regu- 3.6.1 Definitions of sleep spindles
lar respiration and no eye or body movements increased with age;
and 3) between 36 weeks CA and 3 months post-term, only 35%- Sleep spindles in the Rechtschaffen and Kales manual are de-
37% of irregular respiration occurred without eye movements.52 fined only by their 12 to 14 Hz frequency21 and in the Interna-
They observed eye movements were absent in 90% and body tional Glossary of EEG as a “burst at 11 to 15 Hz, but mostly at
movements absent in 98% of all 20-second epochs of regular res- 12-14 Hz generally diffuse but of higher voltage over the central
regions of the head, occurring during sleep and noting that the
Journal of Clinical Sleep Medicine, Vol. 3, No. 2, 2007 209
M Grigg-Damberger, D Gozal, CL Marcus et al
amplitude is usually variable but is mostly below 50 μV in the 13 weeks post-term (mean 6 sec, longest 21 sec); spindles then
adult.”78 Pivik et al defined and visually scored sleep spindles as rapidly decreased, so that by 23 weeks post-term they had a mean
6-7 cycles within a 0.5 second interval; within this interval, at duration of 2.5 sec at 23 weeks post-term, and 1.7 sec by 1 year
least 3 cycles had to be >20 μV for those age 12 or younger and of age.101 Hughes argued that sleep spindles which last >8 sec are
>25 μV for those 13 years or older.79 The Japanese Society of most likely to be seen in an infant 3-4 months post-term. Figure 2
Sleep Research in 2001 defined sleep spindles as “trains of 12 to shows the evolution of sleep spindles in a single normal infant.97
16 Hz waves of >10 μV composed of >6 consecutive waves, or a Sleep spindles are often asynchronous in children younger
train duration >0.5 second.80 than age 2 years.82,99 Kellaway and Fox reported all spindles were
asynchronous in infants 6 to 8 weeks post-term.82 Ellingson and
3.6.2 Evidence for when sleep spindles first appear in infants Peters found that a mean of 49% of spindles were bilaterally sym-
metric and synchronous over C and C at 3 months post-term,
Ellingson and Peters reported that 12-14 Hz sleep spindles first 47% at 6 months, and 70% at 132 month4s post-term.82 Hughes101
appeared 3 to 9 weeks post-term over the central regions (C, C) reported that only 10% of sleep spindles were synchronous at 10
3 4
in both infants born preterm (30 to 33 weeks) and in full-term in- weeks post-term, 20% at 17 weeks, but 70% by one year.
fants.81,82 Metcalf and Jordan found that rudimentary sleep spindles
were first observed 4 weeks post-term and are usually well-devel- 3.6.4 Topographic localization of sleep spindles
oped by 12 weeks post-term.83 Other early infant sleep research-
ers have reported that sleep spindles were well-developed by 12 Only a few channels of EEG are typically recorded in a PSG,
weeks post-term,84,85 43 to 48 weeks CA,86 and during the second so the location of electrode placement is critical. Topographic
month of life.87 Two studies used quantitative frequency analysis analysis aims to establish which EEG channels provide optimal
to confirm that spindle activity initially appears 4 to 9 weeks post- visualization of a particular EEG activity or feature, by simultane-
term.88,89 Louis et al recorded serial all-night home PSGs in 12 ously recording many more channels of EEG than we usually do
healthy post-term infants; they found spindles were absent in 11 in a PSG. The International Glossary of EEG terms reported that
healthy infants at term, but present in all by 2 months post-term.90 sleep spindles were generally recorded diffusely over the scalp,
More recently, 3 longitudinal studies using EEG, PSG, or most but were of higher voltage over the central regions.102 Ellingson
recently magnetoencephalography (MEG) have confirmed that found when simultaneously recording C, C, and C linked to
3 4 z
sleep spindles are usually present by 2 months post-term.49,90,91 ear references, sleep spindles in infants during the first year of
Lutter et al recorded MEG in 18 normal sleeping infants born at life were usually maximal in amplitude over the midline central
term and compared their recordings to the classic EEG patterns (vertex, C) electrode. At times, spindles lateralized, seen only
z
seen in neonates, finding sleep spindles first appeared 46 weeks over left (C) or right (C) central electrode, or occurred simulta-
3 4
CA, manifested by 13 Hz peaks in the EEG power spectrum.92 neously over C, C, and C.81,97
3 4 z
Four studies have examined the topographic localization of
3.6.3 Distinctive features of sleep spindles in infants and children sleep spindles in normal young adult subjects.103-106 Brazier dem-
onstrated spindles were maximal in 32 normal adult subjects, most
Sleep spindles in infants have a particular morphology (a spiky prominent and of highest amplitude just anterior to the midline
negative component and a rounded positive component) in the central (C) electrode,106 the same location reported by Jasper and
first 9 months following birth.49,93-95 Ellingson (1958, 1982) found Andrews.1z03 Zeithofer et al reported spindles were most promi-
when spindles first appear 44 weeks CA, they are low voltage (20 nent over the centroparietal regions.104 McCormick et al studied
μV peak-to-peak recording C-A or C-A) and infrequent (usu- the topographic localization of sleep spindles (and K complexes)
3 2 4 1
ally <3-4 per hour of quiet sleep time.96,97 However, beginning in 8 healthy young adults and found that sleep spindles were de-
46-48 weeks CA, spindle amplitude and density increase to reach tected most often over C (71%) compared to 68% over T and
a mean spindle frequency of 4.2 per min of quiet sleep time (range 63% over F.105 This findi3ng prompted the authors to sugges3t that
2.5 to 6.2) at 3 months post-term96,97 Sleep spindles between ages using a cent3ral electrode would seem the method of choice when
8 to 12 months often have a “comb-like” shape best seen in the performing computer analysis of sleep spindle density in adults.
fronto-temporal EEG derivations.98 The individual waves of the
sleep spindles in infants may sharply peak in the surface-nega- 3.6.5 Sleep spindles occur at two different frequencies in two in-
tive phase, and lack the fusiform amplitude modulation seen in dependent scalp locations particularly in children younger than 13
adults.99 years
Principe and Smith studied whether the amplitude, duration,
and time between spindles during stage 2 sleep changed with age. Gibbs and Gibbs were the first to report the presence of 2
They found that sleep spindles had a mean amplitude of 23 μV, a types of sleep spindles: 12-Hz (“slow”) spindles dominant over
mean duration 0.61 sec, and a mean time between spindles of 66 the frontal region and 14-Hz (“fast”) sleep spindles, most promi-
sec in children aged 3 to 5 years; spindles averaged 27 μV, lasted nent over the central and parietal scalp regions.107 Shinomiya et
0.68 sec, and recurred every 20 sec among the 13-year-olds, com- al identified visually sleep spindles in PSG from 32 normal sub-
pared to 21 μV, 0.71 sec, and 12 sec in the young adult subjects jects (ranging in age from 4 years to 24 years) and calculated the
they studied.100 power spectrum for each sleep spindle within 0.25 Hz between 11
Individual runs of sleep spindles can last as long as 21 sec in and 15 Hz, summing and averaging 20 epochs using Fast Fourier
infants 3 to 4 months post-term.101 Hughes performed a longitudi- Transform analysis.108 They found that 78% of their subjects had
nal study of EEGs on 16 full-term infants from birth to 50 weeks 2 independent scalp locations for sleep spindles: 11.0 to 12.75 Hz
of age and found the maximal duration of spindles occurred at age activity maximal over the frontal scalp region (F, F, or F) and
z 3 4
Journal of Clinical Sleep Medicine, Vol. 3, No. 2, 2007 210