Infant and Pediatric Polysomnography

Transcription

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4 Table of Contents LEARNING OBJECTIVES... 7 INTRODUCTION: EEG REVIEW... 7 PARAMETERS MONITORED PROCEDURES DATA ANALYSIS DISORDERS EVALUATED WITH POLYSOMNOGRAPHY DYSSOMNIAS (DISORDERS OF INITIATING OR MAINTAINING SLEEP) CIRCADIAN RHYTHM DISORDERS NARCOLEPSY IDIOPATHIC HYPERSOMNIA INADEQUATE SLEEP HYGIENE SLEEP-RELATED RESPIRATORY DISORDERS O SLEEP APNEA SYNDROME O UPPER AIRWAY RESISTANCE SYNDROME PARASOMNIAS DISORDERS OF AROUSAL DISORDERS OF SLEEP-WAKE TRANSITION DISORDERS THAT OCCUR DURING REM SLEEP O NIGHTMARES O REM BEHAVIOR DISORDER MEDICAL-PSYCHIATRIC SLEEP DISORDERS MEDICAL - SLEEP-RELATED ASTHMA PSYCHIATRIC O DEPRESSION O PANIC DISORDER NEUROLOGIC - SLEEP-RELATED EPILEPSY OTHERS O BRUXISM O RESTLESS LEGS SYNDROME AND PERIODIC LIMB MOVEMENT DISORDER TREATMENT EEG FOR THE NEONATAL PATIENT THE NORMAL NEONATAL EEG THE ABNORMAL NEONATAL EEG DIFFUSE EEG ABNORMALITIES TRANSIENT METABOLIC DISORDERS INBORN ERRORS OF METABOLISM CNS INFECTIONS FOCAL ACUTE NEUROLOGICAL ABNORMALITIES EEG IN NEONATAL SEIZURES NEONATAL EEG AS A DIAGNOSTIC AND PROGNOSTIC TOOL

5 REFERENCES FINAL EXAMINATION... ERROR! BOOKMARK NOT DEFINED. 5

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7 Infant and Pediatric Polysomnography Course Number CEUs Learning Objectives Upon completion of this continuing education unit, you should be able to: Explain what is meant by EEG, and identify what use these tests have in relation to neonates. Identify which abnormalities can be identified when doing an EEG on neonates. Discuss how neonatal EEGs can be used both as diagnostic and prognostic tools. Introduction: EEG Review Before we begin discussing the intricacies of Neonatal EEG, let s begin with a brief review of just what an EEG is and what information can be obtained from these studies: A polysomnogram consists of a simultaneous recording of multiple physiologic parameters related to sleep and wakefulness (see Picture 1). The interaction of various organ systems during sleep and wakefulness also is evaluated. (The tracings in this course are as good as they can be as they were taken from an original source.) PEDIATRIC POLYSOMNOGRAPHY Suzanne E. Beck, M.D. and Carole L. Marcus, M.B.B.Ch. Sleep Center, The Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania INDICATIONS FOR PEDIATRIC POLYSOMNOGRAPHY Obstructive Sleep Apnea Syndrome (OSAS) OSAS is the most common indication for polysomnography. OSAS is common in the pediatric age group, occurring in approximately 2% of young children (1). The American Academy of Pediatrics recommends that all children be screened by history for snoring (2), recognizing that OSAS is common and is frequently under-diagnosed. Whether or not primary snoring per se results in morbidity is controversial, and is beyond 7

8 the scope of this chapter. However, it has been well established that clinical history alone can not distinguish primary snoring from OSAS in children (2;3). Thus, both the American Thoracic Society (4) and the American Academy of Pediatrics (2) recommend polysomnography as the diagnostic test of choice for children with suspected OSAS. In most cases of pediatric OSAS, children present with signs or symptoms of obstructive breathing patterns during sleep, including snoring, labored breathing, witnessed apnea, gasping, mouth-breathing, or sleeping in unusual positions (such as with the neck hyperextended). Failure to thrive or signs of right sided heart failure may be present in severe cases. Associated daytime symptoms can be difficult to elicit. Unlike adults in whom excessive daytime sleepiness is often the presenting complaint, younger children tend to manifest daytime sleepiness as hyperactivity or inability to concentrate, leading to poor school performance or behavioral issues. Most children with obstructive sleep apnea have a normal physical exam. However, physical findings of retrognathia, oropharyngeal crowding, high arched palate, adenotonsillar hypertrophy, mouth breathing or stertor at rest suggest the need for further evaluation for OSAS. Prematurity, hypotonia (e.g., children with cerebral palsy or muscular dystrophy, Down syndrome) or craniofacial anomalies are risk factors for OSAS. We believe that polysomnography is indicated in any child who snores and has labored breathing during sleep, and who has any predisposing physical exam findings or daytime symptoms. Polysomnography is the gold standard for the diagnosis of OSAS. Other diagnostic studies such as nocturnal oximetry (5), videotaping (6) and nap studies (7) may be helpful if positive, but underestimate the presence of OSAS (2;3), in part because they may not capture REM sleep, during which the majority of obstructive events occur (8) (Figure 1). Finally, direct observation of a sleeping child who is obstructing may be diagnostic of OSAS, but does not quantitate the severity of OSAS and thus cannot predict perioperative risk or the likelihood of persistent abnormalities post-operatively. 8

9 Figure 1 Hypnogram from a 4 year old girl with obstructive sleep apnea syndrome (OSAS). Note that pediatric OSAS occurs primarily in REM sleep (bold bars), with sleep architecture preserved. Central Apnea, Periodic Breathing and Central Hypoventilation Syndromes Pediatric polysomnography is indicated to evaluate infants and children with suspected pathologic central apnea, periodic breathing or central hypoventilation. These children may present with cyanosis, observed apnea during sleep, daytime symptoms, apparent life-threatening events, post-anesthetic respiratory depression or cor pulmonale. It is crucial to monitor end-tidal PCO 2 levels to evaluate for hypoventilation, which if not detected and treated promptly may lead to poor developmental outcomes. Neuromuscular Disorders Polysomnography is useful to evaluate underlying cardiorespiratory function in children with neuromuscular disorders. The timing of the study in the patient s clinical course is variable and is determined by their physician s interpretation of signs and symptoms (9). In addition to evaluation of complaints of difficulty breathing during sleep, a polysomnogram is indicated to detect sleep disordered breathing if there has been a change in growth velocity, developmental progress, daytime symptoms (e.g., sleepiness, headache), pulmonary function (10), development of daytime hypercapnia (11), polycythemia or heart failure. 9

10 Children with respiratory muscle weakness may not show signs of labored breathing during sleep and may not manifest airway obstruction by snoring. CO 2 monitoring is crucial during polysomnography in these patients to evaluate for sleep hypoventilation. Chronic Lung Disease Polysomnography can be used to evaluate for nocturnal hypoventilation and hypoxemia in infants and children with chronic lung disease, as well as to titrate supplemental oxygen. Children with chronic lung disease may have normal arterial oxygen saturation values during wakefulness, but desaturate during sleep (12). In infants with bronchopulmonary dysplasia, maintaining arterial oxygen saturation levels 93% during sleep results in improved growth (13). Unattended overnight pulse oximetry monitoring can be used to assess oxygenation, but may be limited by motion artifact, and oxygen cannot be titrated during these studies; however, home oximetry studies have been proven to underestimate the degree of desaturation (14). Continuous Positive Airway Pressure (CPAP) Ventilator Titration Studies Pediatric polysomnography is used to titrate CPAP and bilevel pressures, as well as home ventilators, in children. One of the main differences in pediatric CPAP titration studies compared to adults is that split night studies (diagnostic studies converted to titrations after demonstration of clinically significant OSAS) are not commonly performed, for several reasons. Often, the children referred to the sleep lab have complex medical issues, and the decision to initiate PAP is multifaceted and is best done in an office setting. In addition, since adenotonsillectomy is the first line of treatment for childhood OSAS, CPAP is often not necessary. Most importantly, placing CPAP on a child for the first time in the middle of the night can be frightening and disturbing for the child. This can result in behavioral issues which will unfavorably influence future CPAP adherence. A behavioral program with desensitization is preferable. For ventilator titration studies, the presence of a respiratory therapist during the study is advisable. Tracheostomy Decannulation Polysomnography is a useful tool to assess functional airway obstruction in children who is thought to be ready for tracheostomy decannulation. In pediatrics, tracheostomies are often placed temporarily, e.g., in a neonate requiring prolonged ventilatory support, or while awaiting adequate airway growth for an infant to tolerate airway reconstruction. Children may breathe adequately when the tracheostomy tube is capped 10

11 during wakefulness, but develop upper airway obstruction due to hypotonia during sleep (15). During these polysomnograms, the patient is monitored initially with the tracheostomy uncapped. The tracheostomy tube is then capped and airflow and end-tidal PCO 2 are monitored via the nose and mouth. It is necessary that oxygen, if required for chronic lung disease, be weaned to low flow so that it can be delivered through a nasal cannula. During the study, careful attention is paid to work of breathing and the presence of obstructive apneas or hypopneas. The lab staff must be trained in tracheostomy care, and should uncap the tracheostomy tube immediately if adverse events are noted. If there is concern that the child may not tolerate the procedure, the study can be done as a bedside study in the intensive care unit. Tracheostomy tube capping studies should only be done in patients who have tolerated capping of the tracheostomy during wakefulness. Ideally, the tracheostomy tube should be downsized prior to the study. Parasomnias A common complaint evaluated in a pediatric sleep center is frequent night awakenings. In most cases, polysomnography is not indicated to evaluate this complaint. Rather, a good history will help determine if these night awakenings are due to sleep terrors or confusional arousals versus behavioral insomnia of childhood or some other cause. However, there are uncommon cases where polysomnography is useful in determining whether there is a pathologic cause precipitating the night waking, such as gastroesophageal reflux or OSAS. In some unusual cases, polysomnography can be helpful in differentiating parasomnias from seizures, hysterical conversion reactions or malingering (e.g., for school avoidance). In these cases, videotaping and good documentation by the sleep technologist are essential. Examining the EEG for epileptiform activity during unusual movements during sleep is useful in differentiating true seizure activity from other motor activity during sleep. Restless Legs Syndrome and Periodic Limb Movement Disorder (PLMD) It is our practice to place limb leads on every infant and child having a polysomnogram. Polysomnography is useful to evaluate for PLMD in young children with symptoms suggestive of restless legs syndrome in whom a definitive history can be hard to elicit; however it is not indicated in straightforward cases. Excessive Daytime Sleepiness In most cases of excessive daytime sleepiness, history, sleep diaries or actigraphy reveal the cause (such as insufficient sleep or poor sleep 11

12 hygiene) and polysomnography is unnecessary. However, polysomnography is indicated in the evaluation of excessive daytime sleepiness if the history elicits suspicion of a pathologic cause such as OSAS, narcolepsy, PLMD or nocturnal seizures. If narcolepsy is suspected, a multiple sleep latency test (MSLT) is indicated. Normal, school-aged children are physiologically unlikely to fall asleep during the day, and thus age-appropriate normative data must be used to interpret the MSLT. The tendency to fall asleep during the day increases with increasing pubertal Tanner stage (16). Some investigators have recommended using MSLTs with naps longer than 20 minutes when young children are studied for research purposes. However, the clinical utility of this longer MSLT protocol for the diagnosis of narcolepsy in children is unknown. Infants usually enter sleep via REM, but in older children, REM-onset naps are suggestive of narcolepsy. In children younger than 5 years of age, in whom napping is commonplace, MSLTs are hard to perform and normative data are unavailable. Ambulatory and Unattended Polysomnography There are no randomized, controlled trials and limited information on pediatric unattended home polysomnography. Jacob et al used a specialized, non-commercial polysomnography system in a carefully selected population in the home, and compared this to in-laboratory recordings. They reported adequate data, with a close correlation between home and laboratory values (17). In contrast, Poels et al studied children aged 2 7 years of age, using a commercial system, and found that only 29% of recordings were successful (18). Goodwin et al reported the feasibility of performing home unattended studies in selected patients as part of a research protocol which involved sending a team to the home to hook up the patient; the initial failure rate was 9% (19). Clearly, further studies are needed. Polysomnography can be challenging in pediatrics because children have a limited ability to cooperate with the setup, and may have trouble sleeping in a strange environment. There are many things a sleep laboratory can do to ease the burden on the child, the family and the technologists, and to improve the diagnostic quality of the polysomnogram. Our approach is to have a mindset of family-centered care, with the parent remaining with the child at all times and the least amount of trauma created for the child. The goal of the lab should be to put the needs of the child first and the needs of the lab and technicians second. The environment in the waiting room and in the bedroom should be child-friendly. In a combined adult-pediatric lab, consider a separate waiting area for children, as they may be intimidated by seeing older or 12

13 ill-appearing adults just before bedtime. A parent should stay with the child, and there should be comfortable accommodations for the parent including a bed in the same room, and shower facilities. The patient bed should be age- and developmentally appropriate (e.g., a crib for infants and toddlers, and side rails for the young or for children with special needs). The type of bed required should be known ahead of time so that the room is ready when the patient arrives. Psychological preparation should be offered to the child and parent prior to the sleep study. This often starts with the clinician who orders the study explaining the procedure and reason for the study in detail. The preparation is reinforced during the scheduling process, where parents are reminded of the procedure and allowed to ask questions. A visit to the sleep lab for a tour prior to the sleep study can be very helpful in easing anxiety associated with the study. Staffing and lab hours might need to be extended for pediatric polysomnograms as children go to bed earlier than adults and need more sleep (e.g., an eight year old typically needs 10 hours for sleep a night). Ideally, there should be a 1:1 technologist:patient ratio during the patient hookup. Some laboratories have used swing shifts during the evening in order to accomplish this. The child should be allowed to sit on the parent s lap and should not be forced to lie down for the hookup. The technician should partner with the parent and the child during the setup and engage the child as much as possible, assigning roles, giving choices, and encouraging age and developmentally appropriate coping strategies. Each step of the hookup should be explained in a child-friendly manner. Lots of praise and smiles should be given out. A few laboratories have child life specialists present during the hookup. The lab should be equipped with a distraction box full of toys such as soap bubble kits, stickers and books to be used during the hook up (20). Although watching television and other electronic screens before bedtime is not good sleep hygiene, making an exception (carefully explained to the parents as such) for polysomnography and having the child watch a video or play video games during hookup can be a powerful distraction. Instead of the hookup proceeding from head to toe, the technician should place the least invasive sensors on first (e.g., leg leads) and save the more noxious ones (EEG, nasal cannula) for later. If necessary, the nasal cannula can be placed after the child falls asleep. During the night, the technologist: patient ratio should be 1:1 or 1:2, depending on the type of study being performed. Children should be allowed to sleep in their usual position. 13

14 PEDIATRIC POLYSOMNOGRAPHIC TECHNIQUES The new American Academy of Sleep Medicine (AASM) scoring manual (21) is the first to clearly delineate pediatric scoring criteria, and the AASM mandates the use of this manual in all accredited sleep labs. The physiologic parameters typically measured during pediatric polysomnography are similar to those measured during polysomnography in adults, with a few exceptions. Recommended sampling rates and filter settings for each channel can be found in the AASM manual (21). The characteristic montage includes: Electroencephalogram (EEG): The AASM recommends F4-M1, C4-M1 and O2-M1; contralateral leads are typically applied as well (F3-M2, C3-M2 and O1-M2). Electromyogram (EMG): Submental and bilateral tibial Electrooculogram (right and left) ECG Nasal pressure Oronasal airflow (thermistry) End-tidal PCO 2 Arterial oxygen saturation (SpO2) with pulse waveform Chest and abdominal wall motion Body position monitor Snoring microphone (optional) Video EEG Monitoring Children have high amplitude brain waves. Thus, EEG recordings may need a sensitivity of μv/mm, as compared to 5 μv/mm in adults. As infants and young children have smaller heads than adults, chin EMG electrodes may need to be placed 1 cm apart rather than 2 cm apart, and electrooculographic leads may need to be placed 0.5 cm from the outer canthi. Because children frequently displace leads during the night, applying redundant leads (such as the contralateral EEG leads, or several monitors of airflow) can obviate the need to awaken the child during the night to reattach leads. Extended EEG montages are used if nocturnal seizures are suspected. However, this procedure extends the setup time. Furthermore, the more leads attached, the more difficulty a child may have falling asleep. Airflow Monitoring The use of multiple measures of airflow is highly recommended, as signals are often lost due to moisture in the sensors, secretions, 14

15 displacement of the sensor by the child or sucking artifact. In particular, it is crucial to include a sensor for oral breathing, as many children with OSAS have an enlarged adenoid and therefore breathe through their mouth. All of the sensors used have both advantages and disadvantages. In our laboratory, we simultaneously measure oronasal thermistry (primarily to detect mouth-breathing), nasal pressure (primarily as a semiquantitative assessment of airflow), end-tidal PCO 2 (primarily as a measure of hypercapnia) and respiratory inductance plethysmography (primarily to assess respiratory effort). We measure nasal pressure and end-tidal PCO 2 using a single nasal cannula with a distal Y-connection to a pressure manometer and a capnometer, and combine this with a very thin, flat thermistor. This system is tolerated by even very young children. For CPAP studies, we use the pneumotachometer within the CPAP circuit as the primary sensor of airflow. Table 1 Airflow Sensors Used In Pediatric Polysomnography Sensor Methodology Advantages Disadvantages Recommendation Thermistor Nasal pressure End-tidal CO 2 Detects changes in temperature Detects changes in nasal pressure Measures PCO 2 Measures oral as well as nasal flow Provides a semiquantitative assessment of airflow Provides a quantitative assessment of the PCO 2. Provides a qualitative rather than quantitative assessment of airflow Poor signal in mouth-breathing patients. Frequently obstructed by secretions etc. Poor signal in mouth-breathing patients. Frequently obstructed by secretions etc. May be oversensitive in detecting airflow. AASM recommends use for detection of apnea AASM recommends use for detection of hypopnea Use as a quantitative measure of PCO 2 rather than a primary measure of airflow. 15

16 Respiratory inductance plethysmography sum signal Derives tidal volume from changes in inductance of coils Pneumotachometer Measurement of airflow by measuring pressure differences across a known resistance Tolerated well as no sensors on face. Quantitative assessment of airflow Difficult to maintain calibrated. Cannot distinguish between obstructive apnea and paradoxing from other causes, e.g., in a young child or child with neuromuscular disease. Requires a snugfitting face mask Useful for assessing respiratory effort in addition to airflow. Use in CPAP studies Oximetry Oximeter signal averaging time should be no more than 3 seconds (21). Children tend to move frequently during sleep, so the monitoring of the pulse waveform in addition to the saturation value is helpful in distinguishing motion artifact from true desaturation. Most pulse oximeters provide an output for the plethysmographic pulse waveform. This output can also be used for more sophisticated analyses, such as the measurement of pulse transit time (22). Oximeters with artifact-reduction algorithms can be very useful (23). Capnometry Most adult sleep laboratories do not measure carbon dioxide (CO 2 ). However, CO 2 measurements are usually obtained in pediatric studies, and can be extremely useful in identifying obstructive hypoventilation (see Scoring section, below). In addition, the measurement of CO 2 is useful in children with chronic lung disease or those receiving ventilatory support. It is especially important to measure CO 2 when supplemental oxygen is initiated in the sleep lab, as some patients may be dependent on their hypoxic drive to breathe. Adding oxygen without monitoring CO 2 may lead to worsening hypoventilation, and clinical deterioration of the patient (24). 16

17 Measurements of CO 2 have been used in two contexts during polysomnography: as an indicator of airflow obstruction, and for quantitative measurement of hypoventilation. As a measure of airflow, end-tidal CO 2 is often oversensitive, and is therefore not recommended other than as an adjunct signal. Thus, in pediatric laboratories, end-tidal PCO 2 is usually measured as an indicator of hypoventilation rather than obstruction. End-tidal PCO 2 can be measured directly from a tracheostomy or endotracheal tube, or as a side-stream measure from a nasal cannula. It is imperative that a good signal, consisting of a plateau during exhalation be obtained (Figure 3). If not, the measure can severely underestimate the actual PCO 2. Furthermore, software should be used that provides the peak PCO 2 rather than random time points during a breath. To maintain a good signal, the technologist needs to be vigilant about clearing secretions and humidity from the line. In children who mouth-breathe, satisfactory signals can sometimes be obtained by placing the cannula over the mouth. It is common to see a single breath with an elevated end-tidal PCO 2 value, especially after sighs or body movements, when previously atelectatic alveoli re-expand. Therefore, the percentage of total sleep time with hypercapnia is more important than the peak end-tidal PCO 2 value for the night. End-tidal PCO 2 values may be inaccurate in patients with obstructive lung disease with long time constants, such as patients with advanced cystic fibrosis. Figure 3 30 second epoch from a polysomnography recording in a 7 month old girl with meningomyelocele with Arnold Chiari malformation and central hypoventilation. Note excellent CO2 waveform and good expiratory plateau. 17

18 An alternative measurement option for evaluating hypoventilation is transcutaneous PCO 2. The transcutaneous electrode warms the skin, thereby arteriolizing the capillary blood flow. The sensor must be moved during the night to prevent skin burns. In contrast to end-tidal measurements, transcutaneous measurements can be slow-reacting, and therefore provide a trend rather than a breath-by-breath measurement. However, transcutaneous measurements may be preferable to end-tidal measurements in children with advanced obstructive lung disease, infants with rapid respiratory rates, children who breathe through their mouth and children receiving CPAP, in whom the CPAP airflow may interfere with end-tidal measurements. Many children, particularly those less than three years of age, have a pattern of persistent, partial upper airway obstruction associated with hypercapnia and/or hypoxemia, rather than cyclic discrete obstructive apneas. This has been termed obstructive hypoventilation. (4) Most studies comparing end-tidal and transcutaneous PCO 2 to arterial samples have been performed in the intensive care unit or during anesthesia, rather than in sleep laboratories. In general, these studies show a good correlation between the transcutaneous/end-tidal and arterial values, with a small bias evident in subjects without lung disease. In general, end-tidal values tended to underestimate arterial CO 2, with the largest discrepancies occurring in hypercapnic subjects or in subjects with respiratory disease. Transcutaneous values tended to have a smaller bias compared to arterial values than the end-tidal PCO 2 measurements, but tended to overestimate the PCO 2. Respiratory Effort Chest and abdominal wall motion can be measured in a number of ways. Respiratory inductance plethysmography is the preferred method, and is typically used in the uncalibrated mode in children, as calibration procedures would need to be repeated after body movements. Other sensors that have been used include piezo-electric belts, which are provided with many commercial polysomnography systems, intercostal EMG, and esophageal pressure monitoring. In one non-randomized study of normal children, paradoxical breathing was seen much more commonly with piezo-electric belts than with respiratory inductance plethysmography (26). Esophageal pressure monitoring is rarely used as it is invasive, and the nasal pressure flow signal is often used as a surrogate when the upper airway resistance syndrome is suspected. 18

19 Body Position Body position is frequently measured during polysomnography, although the measurement of body position is less important in young children than in adults, as OSAS is less positional (27;28). Esophageal ph Esophageal ph is occasionally measured to determine whether gastroesophageal reflux is contributing to night wakings, apnea or desaturation. ph probe insertion is more invasive than the rest of the leads on a polysomnogram and takes specialized skill; placement must be confirmed by radiograph. The percentage of total sleep time with ph < 4, and the number and length of ph drops < 4 can be quantified, and reviewed for an association with respiratory disturbances. Videotaping Videotaping can be extremely helpful in the assessment of parasomnias, seizures and unusual respiratory events. In rare cases, such as a very autistic child who refuses many of the monitoring leads, videotaping can be a valuable diagnostic tool. It may also be useful at times by revealing unusual parental interactions. In the authors experience, videotapes and technologist s observations have revealed cases where a lead radiology vest was used by parents to restrain a neurologically-impaired child s nocturnal movements; a cardboard box over the child s head was substituted for an oxygen hood; a teenager complaining of daytime fatigue wrapped her entire face and body in a sheet cocoon, resulting in increased inspired and end-tidal PCO 2 levels; and an infant admitted with cyanotic spells had a bible placed over his face during sleep. PEDIATRIC POLYSOMNOGRAPHY SCORING Pediatric scoring rules are detailed in the AASM manual (21). This chapter will highlight the differences between adult and pediatric scoring rules. Sleep Architecture The EEG changes considerably with age. The new AASM rules, with a few minor modifications, are applicable to pediatric patients older than 2 months post-term. In infants younger than 2 months of age, Anders criteria, which rely heavily on behavioral observations in addition to EEG, should be used (29). Sleep spindles, K complexes and slow wave activity are typically first noted at 2 3 months, 4 6 months and

20 months post-term, respectively, and thereafter become more prominent. If these distinguishing EEG characteristics cannot be discerned after 2 months of age, sleep should be scored as stage N (nonrem) and R (REM). By 6 months of age, most infant studies can be scored using the adult nonrem stages (i.e., stages N1, N2 and N3). However, the EEG continues to show differences from the adult EEG, with a higher amplitude, and a slower dominant posterior rhythm than the alpha rhythm seen in adults. For further details, please see reference (30). It should be recognized that the amount of REM and slow wave sleep changes dramatically during infancy, childhood and adolescence. In infants, it is normal to enter sleep via REM. The amount of REM sleep as a percentage of total sleep time decreases during infancy and childhood. The amount of slow wave sleep also decreases during childhood, particularly during adolescence. Arousals Arousal scoring rules are the same for children as for adults. Children have a higher arousal threshold than adults, so it is common for them to have obstructive events that are not associated with EEG arousals (31). Respiratory Respiratory scoring in children is quite different from that in adults. Pediatric scoring must be used for children 12 years of age. As there is a paucity of data for adolescents, the use of pediatric scoring criteria for teenagers between years of age is optional. However, small studies that incorporated adolescents indicate that their breathing patterns during sleep are similar to that of younger children, and hence, the use of pediatric scoring criteria would be appropriate (32 35). Adult criteria are used for patients 18 years of age. In adults, apneas and hypopneas are only scored if they are 10 seconds duration. Children have a faster respiratory rate than adults, and a lower functional residual capacity. They are therefore more likely to desaturate and suffer physiologic consequences from brief apneas. Because of this, obstructive apneas and hypopneas are scored if they are at least 2 breaths duration, even if they are < 10 seconds duration (21). Hypopneas are defined as a 50% reduction in airflow associated with either arousal or 3% desaturation (21). In contrast to adults, the AASM does not recommend any alternative Medicare scoring rules for hypopneas. Obstructive events in children occur primarily during REM sleep (8). Thus, if sufficient REM sleep is not obtained during a polysomnogram, the degree of OSAS is likely to be underestimated. 20

21 Figure 5 30 second epoch from a polysomnography recording in a 4 month old infant with OSAS. Note the short duration (4.5 5 seconds) of the obstructive apneas, associated with paradoxical chest and abdominal wall motion and desaturation but no arousal. Ander s sleep staging was used. Some children, especially very young children, have a pattern of persistent partial upper airway obstruction associated with hypercapnia and desaturation, rather than discrete obstructive apneas or hypopneas. This pattern has been termed obstructive hypoventilation (4) (Figure 6). Obstructive hypoventilation differs from hypopneas in that a reduction in airflow may not be detected using usual airflow sensors, and events may be very long (many minutes). It can be differentiated from hypoventilation secondary to central nervous system abnormalities or pulmonary disease by the presence of snoring and paradoxical respiratory efforts. In addition, although hypoventilation from any cause is usually worse during sleep than wakefulness, in patients with obstructive hypoventilation the discrepancy between sleep and wakefulness is very large. 21

22 Figure 6 30 second epoch in a 6 year old otherwise healthy girl with obstructive hypoventilation showing overall preserved nasal airflow with prolonged paradoxical chest and abdominal wall motion, elevated end tidal CO2 and prolonged desaturation. Respiratory effort related arousals (RERA) are not scored in all laboratories. Scoring details can be found in the AASM manual (21). The prevalence of the upper airway resistance syndrome during childhood is not known, but many practitioners believe that it is rare, and that these children tend to exhibit mild forms of classic sleep-disordered breathing that can be detected using conventional polysomnographic acquisition and scoring techniques, including the monitoring of nasal pressure and end-tidal PCO 2. Central apneas are common during sleep in children. Children have an active Hering-Breuer reflex (compensatory central respiratory pauses following the stimulation of pulmonary stretch receptors), and frequently have central apneas following sighs and movements, as well as during REM sleep. Central apneas or periodic breathing at sleep-onset is relatively uncommon. Because long central apneas are frequently seen in normal children, central apneas are only scored if they are 20 seconds duration, or shorter, but associated with either arousal or 3% desaturation (21). 22

23 Periodic breathing occurs relatively frequently in premature infants or children at high altitude, and is occasionally seen in older children with central nervous system abnormalities, or as a brief normal phenomenon at sleep onset. Periodic breathing is defined as >3 episodes of central apnea lasting > 3 seconds each, and separated by 20 seconds of normal breathing (21). It is different from Cheyne-Stokes breathing in that it typically lacks a waxing and waning pattern. Figure 7 60 second epoch PSG recording in a 4 month old infant with periodic breathing showing pathological periodic breathing, with characteristic repeated short central apneas and desaturations. Note also high amplitude delta waves, typically seen in infants. Central and obstructive apneas have very different pathophysiologic mechanisms and treatments. Hence, the obstructive and central event indices should be presented separately, rather than being combined as a respiratory disturbance index. Mixed apneas and hypopneas are included in the obstructive index. 23

24 REPRODUCIBILITY OF PEDIATRIC POLYSOMNOGRAPHIC RESULTS Several studies have examined polysomnographic reproducibility. Infants do not display a first night effect (36). When studied on 2 consecutive nights, older children have an increased sleep latency and decreased sleep efficiency on the first night, and may also show changes in REM sleep, consistent with a first night effect (37;38). However, differences in respiratory parameters from one night to another are minimal, and not clinically significant (37;38). When polysomnography was repeated over several weeks, or even after a year in children with primary snoring, some very minor changes were noted in the apnea hypopnea index, but not enough to be clinically important (39;40). Therefore, one night of polysomnography is adequate for clinical purposes, although several nights of recording may be needed in order to evaluate sleep architecture for research purposes. CLINICAL IMPLICATIONS OF PEDIATRIC POLYSOMNOGRAPHIC SCORING It should be emphasized that these are statistical norms rather than clinical criteria upon which to base treatment decisions. There are very few studies assessing the polysomnographic predictors of morbidity in children, and these outcome studies need to be performed before clear clinical recommendations can be made. That being said, children do tend to have clinical complications of OSAS with a much lower apnea hypopnea index (AHI) than adults, and many centers will treat children with an AHI in the 2 5/hr range. An AHI of 10/hr, which is considered mild in adults, is generally considered to be moderately severe in children (39). An NIH-funded, multicenter randomized trial (the Childhood Adenotonsillectomy [CHAT] study) is currently underway to evaluate neurocognitive morbidity associated with mild to moderate OSAS in children, and whether surgical intervention influences neurocognitive outcomes. Thus, more information should become available over the next few years. Pediatric polysomnography is the diagnostic study of choice to evaluate for obstructive sleep apnea in children, and to evaluate cardiorespiratory function in infants and children with chronic lung disease or neuromuscular disease when indicated. It is helpful to investigate atypical cases of parasomnias. It is important to understand that children are not just small adults when being studied in a sleep lab; they require a child friendly atmosphere and approach, need smaller and specialized equipment, and due to developmental and physiological differences from 24

25 adults, have age-adjusted rules for the scoring and interpretation of polysomnograms. Table 2 Typical Sleep Architecture Values For Normal Children Aged 1 18 Years Parameter Usual value References Sleep efficiency (%) 89%, large variability (26;41;42) Sleep latency (min) 23, large variability (26;41;42) REM latency (min) (< 10 years of age) (41;42) (> 10 years of age) Arousal index 9 16 (26;41;42) (N/hr) Stage N1 (%TST) 4 5 (26;34;42) Stage N2 (%TST) (26;34;42) Stage N3 (%TST) (< 10 years of age) (26;34;42) 20 (> 10 years of age) Stage R (%TST) (can be higher in young children) (26;34;42) Table 3 Recommended Normative Polysomnographic Values For Children Aged 1 18 Years Parameter Obstructive AHI (N/hr) Central apnea index (N/hr) Time with SpO 2 < 90% (%TST) Usual value Comments and references 1.4 (26;33;41;43) (41) (26) Only study using AASM criteria SpO 2 nadir (%) 91 (33;34) (Data from (26) were discrepant, with a value of 86%) 25

26 Time with peak PCO 2 50 mm Hg (%TST) Periodic limb movement index (N/hr) > 25 Data are from (41). Values from (34) were much lower than references (33;41) and are not consistent with the authors personal experience; reference (33) did not use infrared capnometry and is therefore not included. Summary Pediatric polysomnography is the diagnostic study of choice to evaluate for obstructive sleep apnea in children, and to evaluate cardiorespiratory function in infants and children with chronic lung disease or neuromuscular disease when indicated. It is helpful to investigate atypical cases of parasomnias. It is important to understand that children are not just small adults when being studied in a sleep lab; they require a child friendly atmosphere and approach, need smaller and specialized equipment, and due to developmental and physiological differences from adults, have age-adjusted rules for the scoring and interpretation of polysomnograms. References 1. Redline S, Tishler PV, Schluchter M, Aylor J, Clark K, Graham G. Risk factors for sleep-disordered breathing in children. Associations with obesity, race, and respiratory problems. Am J Respir Crit Care Med. 1999;159: American Academy of Pediatrics. Clinical practice guideline: diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. 2002;109(4): Schechter MS. Technical report: diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. 2002;109(4):E American Thoracic Society. Standards and indications for cardiopulmonary sleep studies in children. Am J Respir Crit Care Med. 1996;153: Brouillette RT, Morielli A, Leimanis A, Waters KA, Luciano R, Ducharme FM. Nocturnal pulse oximetry as an abbreviated testing modality for pediatric obstructive sleep apnea. Pediatrics. 2000;105(2): Sivan Y, Kornecki A, Schonfeld T. Screening obstructive sleep apnoea syndrome by home videotape recording in children. Eur Respir J. 1996;9(10): Marcus CL, Keens TG, Ward SL. Comparison of nap and overnight polysomnography in children. Pediatr Pulmonol. 1992;13(1): Goh DYT, Galster P, Marcus CL. Sleep architecture and respiratory disturbances in children with obstructive sleep apnea. Am J Respir Crit Care Med. 2000;162:

27 9. Finder JD, Birnkrant D, Carl J, Farber HJ, Gozal D, Iannaccone ST, et al. Respiratory care of the patient with Duchenne muscular dystrophy: ATS consensus statement. Am J Respir Crit Care Med. 2004;170(4): Toussaint M, Steens M, Soudon P. Lung function accurately predicts hypercapnia in patients with Duchenne muscular dystrophy. Chest. 2007;131(2): Hukins CA, Hillman DR. Daytime predictors of sleep hypoventilation in Duchenne muscular dystrophy. Am J Respir Crit Care Med. 2000;161(1): Moyer-Mileur LJ, Nielson DW, Pfeffer KD, Witte MK, Chapman DL. Eliminating sleep-associated hypxemia improves growth in infants with bronchopulmonary dysplasia. Pediatrics. 1996;98: Groothuis JR, Rosenberg AA. Home oxygen promotes weight gain in infants with bronchopulmonary dysplasia. Am J Dis Child. 1987;141(9): Wiltshire N, Kendrick AH, Catterall JR. Home oximetry studies for diagnosis of sleep apnea/hypopnea syndrome: limitation of memory storage capabilities. Chest. 2001;120(2): Tunkel DE, McColley SA, Baroody FM, Marcus CL, Carroll JL, Loughlin GM. Polysomnography in the evaluation of readiness for decannulation in children. Arch Otolaryngol Head Neck Surg. 1996;122(7): Carskadon MA, Harvey K, Duke P, Anders TF, Litt IF, Dement WC. Pubertal changes in daytime sleepiness. Sleep. 1980;2(4): Jacob SV, Morielli A, Mograss MA, Ducharme FM, Schloss MD, Brouillette RT. Home testing for pediatric obstructive sleep apnea syndrome secondary to adenotonsillar hypertrophy. Pediatr Pulmonol. 1995;20(4): Poels PJ, Schilder AG, van den BS, Hoes AW, Joosten KF. Evaluation of a new device for home cardiorespiratory recording in children. Arch Otolaryngol Head Neck Surg. 2003;129(12): Goodwin JL, Enright PL, Kaemingk KL, Rosen GM, Morgan WJ, Fregosi RF, et al. Feasibility of using unattended polysomnography in children for research--report of the Tucson Children s Assessment of Sleep Apnea study (TuCASA) Sleep. 2001;24(8): Zaremba EK, Barkey ME, Mesa C, Sanniti K, Rosen CL. Making polysomnography more child friendly: a family-centered care approach. J Clin Sleep Med. 2005;1(2): Iber C, editor. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specification. American Academy of Sleep Medicine; Ref Type: Serial 22. Katz ES, Lutz J, Black C, Marcus CL. Pulse transit time as a measure of arousal and respiratory effort in children with sleep-disordered breathing. Pediatr Res. 2003;53(4): Brouillette RT, Lavergne J, Leimanis A, Nixon GM, Ladan S, McGregor CD. Differences in pulse oximetry technology can affect detection of sleep-disorderd breathing in children. Anesth Analg. 2002;94(1 Suppl):S47 S Marcus CL, Carroll JL, Bamford O, Pyzik P, Loughlin GM. Supplemental oxygen during sleep in children with sleep- disordered breathing. Am J Respir Crit Care Med. 1995;152(4 Pt 1): [PubMed] 27

28 25. Redline S, Budhiraja R, Kapur V, Marcus CL, Mateika JH, Mehra R, et al. The scoring of respiratory events in sleep: reliability and validity. J Clin Sleep Med. 2007;3(2): Traeger N, Schultz B, Pollock AN, Mason T, Marcus CL, Arens R. Polysomnographic values in children 2 9 years old: additional data and review of the literature. Pediatr Pulmonol. 2005;40(1): Fernandes do Prado LB, Li X, Thompson R, Marcus CL. Body position and obstructive sleep apnea in children. Sleep. 2002;25(1): Dayyat E, Maarafeya MM, Capdevila OS, Kheirandish-Gozal L, Montgomery- Downs HE, Gozal D. Nocturnal body position in sleeping children with and without obstructive sleep apnea. Pediatr Pulmonol. 2007;42(4): Anders T, Emde R, Parmelee A, editors. A manual of standardized terminology, techniques and criteria for scoring of states of sleep and wakefulness in newborn infants. UCLA Brain Information Service, NINDS Neurological Information Network; Ref Type: Serial 30. Grigg-Damberger M, Gozal D, Marcus CL, Quan SF, Rosen CL, Chervin RD, et al. The visual scoring of sleep and arousal in infants and children. Journal of Clinical Sleep Medicine. 2007;3(2): McNamara F, Issa FG, Sullivan CE. Arousal pattern following central and obstructive breathing abnormalities in infants and children. J Appl Physiol. 1996;81: Acebo C, Millman RP, Rosenberg C, Cavallo A, Carskadon MA. Sleep, breathing, and cephalometrics in older children and young adults. Chest. 1996;109: Marcus CL, Omlin KJ, Basinki DJ, Bailey SL, Rachal AB, Von Pechmann WS, et al. Normal polysomnographic values for children and adolescents. Am Rev Respir Dis. 1992;146(5 Pt 1): Uliel S, Tauman R, Greenfeld M, Sivan Y. Normal polysomnographic respiratory values in children and adolescents. Chest. 2004;125(3): Tapia IE, Karamessinis L, Bandla P, Huang J, Kelly A, Pepe M, et al. Polysomnographic values in children undergoing puberty: Pediatric vs. adult respiratory rules in adolescents. Sleep. 36. Rebuffat E, Groswasser J, Kelmanson I, Sottiaux M, Kahn A. Polygraphic evaluation of night-to-night variability in sleep characteristics and apneas in infants. Sleep. 1994;17(4): Li AM, Wing YK, Cheung A, Chan D, Ho C, Hui S, et al. Is a 2-night polysomnographic study necessary in childhood sleep-related disordered breathing? Chest. 2004;126(5): Scholle S, Scholle HC, Kemper A, Glaser S, Rieger B, Kemper G, et al. First night effect in children and adolescents undergoing polysomnography for sleep-disordered breathing. Clin Neurophysiol. 2003;114(11): Katz ES, Greene MG, Carson KA, Galster P, Loughlin GM, Carroll J, et al. Nightto-night variability of polysomnography in children with suspected obstructive sleep apnea. J Pediatr. 2002;140(5): Marcus CL, Hamer A, Loughlin GM. Natural history of primary snoring in children. Pediatr Pulmonol. 1998;26:

29 41. Montgomery-Downs HE, O Brien LM, Gulliver TE, Gozal D. Polysomnographic characteristics in normal preschool and early school-aged children. Pediatrics. 2006;117(3): Mason TB, Teoh L, Calabro K, Traylor J, Karamessinis L, Schultz B, et al. Rapid eye movement latency in children and adolescents. Pediatr Neurol. 2008;39(3): Witmans MB, Keens TG, Davidson Ward SL, Marcus CL. Obstructive hypopneas in children and adolescents: normal values. Am J Respir Crit Care Med. 2003;168(12):

30 Introduction Polysomnography (PSG) is used to evaluate abnormalities of sleep and/or wakefulness and other physiologic disorders that have an impact on or are related to sleep and/or wakefulness. Picture 1. Typical polysomnogram tracing. The burst of electromyogram activity recorded from the left tibialis anterior muscle was caused by a periodic movement of sleep. Parameters Monitored By international standards, a polysomnogram must have a minimum of 4 neurophysiologic channels. 1. One electroencephalography (EEG) channel (central with an ear reference provides the best amplitude) to monitor sleep stage 2./3. Two electrooculogram (EOG) channels to monitor both horizontal and vertical eye movements (electrodes are placed at 30

31 the right and left outer canthi, 1 above and 1 below the horizontal eye axis) 4. One electromyography (EMG) channel (usually chin or mentalis and/or submentalis) to record atonia of rapid eye movement (REM) sleep Other parameters often monitored include the following: Additional EEG channels, particularly in patients with sleeprelated epilepsy Additional EMG channels, particularly anterior tibialis, to detect periodic limb movements of sleep Airflow Electrocardiogram Pulse oximetry Respiratory effort Sound recordings to measure snoring Optional parameters include the following: Continuous video monitoring of body positions Core body temperature Incident light intensity Penile tumescence Pressure and ph at various esophageal levels Procedures In 1992, the Office of Technology Assessment of the Agency of Health Care Policy and Research recommended, in an evidence-based assessment, two tests as having been studied sufficiently. Both tests are performed in a sleep laboratory. 1. Overnight polysomnography (PSG) is an overnight recording of the patient s sleep. 2. Multiple sleep latency testing (MSLT) records multiple naps throughout a day. Standard sleep studies usually include both tests, PSG (may be performed over several nights) followed by MSLT the next day. Limitations usually stem from the fact that recording conditions may not reflect what happens during a regular night in the patient s home. Although diagnosing a sleep problem on the basis of a recording over a single night is common practice, some authorities caution that more than one night of recording may be necessary, so the patient may become comfortable with unfamiliar surroundings and sleep more naturally. This 31

32 effect is greatest on the first night in the sleep laboratory ( first night effect ). Sporadic events may be missed on a one-night PSG. External factors that disturb the subject s sleep may be present in the home but absent from the controlled environment of the sleep lab. Patient preparation is important so that the patient sleeps naturally. Patient instructions include the following: Maintain regular sleep-wake rhythm Avoid sleeping pills Avoid alcohol Avoid stimulants, including medications for narcolepsy Avoid strenuous exercise on the day of PSG testing High costs and long waiting lists have prompted the exploration of alternative methods of evaluation. Although the following studies may have usefulness in specific clinical situations, Bloch concludes that their role compared to conventional sleep studies remains controversial. Ambulatory monitoring with portable equipment Daytime PSG Simplified sleep studies with limited subsets of monitored parameters Data Analysis Automatic, computer-based systems often are employed in clinical and research settings. However, standard analysis still consists of tedious and time-consuming review and scoring of either paper tracings or recordings projected on a computer monitor. Overnight parameters (e.g., times of lights on/off, total time in bed, total sleep time) are collected. The overnight recording is divided into epochs of approximately 30 seconds. The standard EEG, EMG, and EOG recordings are evaluated, and the predominant stage of sleep (according to the manual of Rechtschaffen and Kales) then is assigned to the entire epoch. Total time and relative proportion of the night spent in each of the 6 stages and in REM and non-rem sleep are calculated. Latencies to REM and slow-wave sleep (SWS) are reported. Special neurophysiologic events (e.g., epileptic events, intrusion of alpha into sleep, periodic activity of tibialis anterior) are reported. Respiratory activity (e.g., apneic or hypopneic episodes, oxygen saturation) is 32

33 correlated with sleep stages. Other parameters such as body position, gastroesophageal reflux, bruxism, and penile tumescence are recorded. If a sleep apnea syndrome is diagnosed, a trial and titration of continuous positive airway pressure or a trial of an oral appliance may be undertaken, either in a partial-night or second-night PSG recording. Disorders Evaluated with Polysomnography Dyssomnias (disorders of initiating or maintaining sleep) Circadian rhythm disorders Narcolepsy Idiopathic hypersomnia Inadequate sleep hygiene Sleep-related respiratory disorders o Sleep apnea syndrome o Upper airway resistance syndrome Parasomnias Disorders of arousal Disorders of sleep-wake transition Disorders that occur during REM sleep o Nightmares o REM behavior disorder Medical-psychiatric sleep disorders Medical - Sleep-related asthma Psychiatric o Depression o Panic disorder Neurologic - Sleep-related epilepsy Others o Bruxism o Restless legs syndrome and periodic limb movement disorder Treatment Treatment is determined by the disorder diagnosed by PSG and/or MSLT. EEG for the Neonatal Patient Over the past several decades, electroencephalography (EEG) in newborn infants has become valuable as a serial, noninvasive screening tool for infants at high risk of perinatal injuries. The brain dynamics and 33

34 connectivity in different states (awake or asleep) can be defined, and a whole range of acute or chronic cerebral disorders can be identified. Such information often reveals presymptomatic or subclinical conditions. The EEG prognostic value at the time of continuous development is often greater than at a later stage. EEG testing can provide reassurance to the physician and parents at a time of potential catastrophic damage. The continuous changes that occur during early brain development are often associated with striking changes in EEG patterns over short periods. This makes it difficult to interpret EEG results, which can discourage the use of EEG testing. Given the close relationships between certain morphological aspects of the developing brain and EEG results, gestational age (GA) can be reliably estimated (to ±1 wk) by EEG criteria. In fact, CNS development of the immature brain proceeds at about the same rate during fetal development as in the postnatal environment. The physiological substrate for these early EEG patterns is unknown, but is probably derived from cortical generators that are strongly influenced by subcortical (primarily thalamic) afferent input. Rapid maturation of these structures (and not the corpus callosum) is most likely responsible for the interhemispheric synchrony that occurs close to full-term GA; in particular, rapid dendritic spine development and synaptogenesis are typical of the last month of fetal development. The complex development of cerebral sulci during this same period is probably responsible for the neonatal EEG results showing complex, more definitive patterns at term. At this age, easily recognizable and organized activity patterns appear. These continue with little change during the first month of life and are strictly characteristic of neonatal EEG. There are several technical considerations when recording from a small (neonate) scalp. High skin resistance impedes low-resistance scalp-toelectrode contact. The state of activity (awake or quiet vs. active sleep) can be selectively bound to certain aspects of pathology. It is important to annotate the tracing with particular attention to the presence and type of eye movements, facial movements, respiration (regular or irregular), sucking, crying, grimacing, and so on. Extracerebral monitors are needed in routine recordings, including at least electrooculogram (EOG), respiration rate measurement, and electrocardiogram (ECG). Only a reduced number of scalp electrodes, generally never more than the set in a 16-channel recording, are applicable. A low time constant ( seconds) is preferable to record the low-frequency background activity. Slow paper speed maximizes the slow background and the degree of interhemispheric synchrony. 34

35 The Normal Neonatal EEG In the full-term born infant (FTBI), ultradian sleep and waking cycles are well defined and easy to detect with polygraphic and behavioral criteria. On EEG, wakefulness characterized by eye opening, crying, and vigorous motor behavior accompanied by irregular vital signs on recordings (ECG, respiration) is marked by a low-amplitude activity and discontinuous 4-7 cps theta activity interspersed with low-voltage delta rhythms. Hence, the French name activité moyenne. Active sleep (AS), the antecedent of rapid eye movement (REM) sleep, is usually indicated by irregular respiratory patterns with interspersed, brief apneic episodes that often precede clusters of eye movements. Contrary to adult physiology, prominent, subtle motor activity, especially of the face (e.g., grimacing, smiling), accompanies this state. These results are often interpreted as seizure activity by the inexperienced reader. On EEG, two patterns are observable, as follows: 1. A continuous, low- to medium-voltage background with theta and delta activity and occasional anterior sharp-waves that occur primarily at sleep onset, or 2. A lower amplitude, more continuous theta background is mostly seen between periods of quiet sleep (QS). The latter non-rem sleep is marked by a discontinuous pattern (tracé alternante) that is characterized by bursts of high-amplitude (50-20 mv) synchronous delta activity and separated by intervals of lower mixed activity that resemble wake or AS activity (see Picture 2). Picture 2: Quiet sleep non rapid eye movement tracé alternante 35

36 Near the end of the first month, a more diffuse pattern usually appears, consisting of continuous, high- to moderate-amplitude slow activity that is not seen in the preterm infant. A high degree of synchrony between burst and interburst activity is desirable at term. This usually confirms normal maturational patterns. Several morphological figures may occur with variable frequency. Random sharp-waves, most commonly temporal or rolandic, are sporadically seen in QS. Nonrolandic, repetitive, highly focal spikes confined to a single location that occur during wakefulness usually indicate abnormalities. A burst of frontal delta and synchronous, frontal sharp waves are still abundant in the FTBI during AS. Spindle delta bursts (brushes) are seen with decreasing frequency in the FTBI and are usually confined to the central and temporal leads during QS. This state is the most vulnerable, being susceptible to various minor CNS insults that are only transiently apparent, depending on their expression. It is important to perform prolonged recordings, especially in stressed infants as they are likely to express less QS. Several important milestones characterize EEG maturation patterns during the first months of life. The newborn progressively develops a circadian rhythm, resulting from the interaction of endogenous factors with external synchronizers such as light, eating, and sensory stimulation over the course of a day. At approximately the third month, sleep efficiently occurs in nocturnal intervals of at least 8 hours, reflecting mother-child interactions and the established activity of endogenous pacemakers. With regard to EEG results, several important changes accompany this phase. From the second week of life, slow and continuous background activity (consisting of increasing amplitude delta waves whose frequency also decreases with the approaching first month of life) progressively replaces the discontinuous pattern (tracé alternante) that is typical of QS. Typical EEG characteristics disappear within the second month of life, including slow frontal biphasic spikes (encoches frontales) and negative rolandic spikes. The newborn still falls asleep in AS until the end of the third month. AS decreases from 50% to 40% by the end of the fourth month; likewise, QS progressively increases and becomes more defined due to the appearance of EEG hypnic features that are typical of adults. Vertex waves can be noted in the rolandic regions after the third month; sleep spindles appear earlier, at about the sixth week, over the central regions. The first sleep spindling samples are slower in frequency and more anteriorly distributed in newborns compared with older infants. These infrequently appear at the beginning of QS as rudimentary, low-voltage 36

37 (<25 mv), immature, asymmetric, and asynchronous Hz EEG waveforms. The length, amplitude, and synchrony of these spindling samples increase during the first year of life and are more prominent in females and small for gestational age newborns, especially those with neonatal respiratory distress. Spindling maturation is prognostically valuable: their absence at the third month indicates abnormal maturation (e.g., hypothyroidism, severe patterns of mental retardation). At the same time, the sawtooth waves that are typical of adult REM sleep make their first appearance in AS. Around the sixth postnatal week, 75 mv occipital sharp waves characterize AS and increase in frequency from 2 to 4 Hz toward the end of the third month. At 3 months, a clearly defined 3-4 Hz, mv occipital rhythm appears during wakefulness; this is interrupted by eye opening. It progressively evolves at about 5 months to a faster frequency of 6-7 Hz. The Abnormal Neonatal EEG Even more than in other epochs of life, in neonates the abnormal neonatal EEG has a prognostic value as opposed to a diagnostic value. Rarely, specific EEG patterns correspond to typical syndromes. Prognostic value can be increased with the following methods: Early recordings, possibly within the first 48 hours of life - Markedly abnormal EEG patterns usually last for a relatively short time, followed by less abnormal or even normal patterns despite the absence of clinical resolution. Prolonged recordings to include samples of different activity states - QS, for instance, is far more likely to show valuable maturation pattern abnormalities and yet is less likely to occur within short recording intervals in a compromised infant. Serial EEGs obtained at short intervals to assess the rapid changes that are likely to occur in rapidly maturing, high-risk infants - Normalization of a previously abnormal pattern may indicate a minimal impact of a brain insult on maturation. Conversely, progressive deterioration of previously normal or moderately abnormal patterns favors the possibility of long-term neurological sequelae. Because EEG abnormalities in neonates cover a broad spectrum, any classification is difficult and, in some cases, arbitrary. One possibility for classification would be to distinguish between diffuse and focal abnormalities and to categorize separately ictal and paroxysmal patterns in the presence of neonatal convulsions. 37

38 Diffuse EEG Abnormalities With regard to severity and prognosis, severe and irreversible abnormalities should be distinguished from moderate, reversible abnormalities. Severe abnormalities correspond to two main EEG patterns, inactive and paroxysmal, both of which are accompanied by a lack of sleep cycles and a lack of reactivity to internal or environmental stimuli. The inactive or isoelectric pattern consists of cerebral activity below 10 mv that is continuously present throughout the record. Brief intervals of low-voltage activity, which are located over the posterior head regions, may occasionally be present. This pattern may occur in varying clinical conditions and often occurs with the following states: Early severe asphyxia or massive hemorrhage Severe inborn metabolic deficits CNS bacterial or viral infections Gross congenital malformations (see Picture 3) Drug-induced state Hypothermia Postictal recording Picture 3 Inactive or isoelectric pattern In the absence of a drug-induced state, hypothermia, or postictal recording, the prognosis is poor but not necessarily fatal. The paroxysmal or burst suppression EEG pattern is characterized by intervals of inactive background activity (<10-15 mv) that alternate with 38

39 synchronous or asynchronous activity bursts. These include primarily high-voltage, irregular slow waves with or without sharp components (see Picture 4). This pattern, which carries a highly unfavorable prognosis, must be clearly distinguished from a full-term newborn s tracé alternante and a preterm infant s tracé discontinue (TD), both of which are normal patterns. Serial recordings are essential to reach a reliable prognosis. Certain conditions (e.g., Aicardi syndrome or uncommon dysgenetic conditions that involve the corpus callosum) rarely present as hemihypsarrhythmia. Picture 4 Paroxysmal or burst suppression EEG. Notice prominent bursts of paroxysmal activity interspersed with an inactive background activity. 39

40 Severe but reversible diffuse abnormalities can occur and are exemplified by the so-called low-voltage pattern throughout the EEG record. QS and AS are only distinguishable by the slightly higher voltage in QS, where mixed frequencies under mv are almost continuously recorded. This finding and a diffuse delta pattern with minimal theta rhythms throughout the entire EEG record hold an intermediate prognosis. When the abnormalities are compatible with these changes seen in sleep, they are generally considered moderate and reversible. Diffuse EEG abnormalities can also be seen as irregularities in maturational indices and organizational states. In addition to the patterns of profound disruption to the ability to organize cyclic states (which are typical of the most severe abnormalities), several patterns of EEG dysmaturity can be recognized and identified. In newborns who are small for their gestational age, transient or persistent dysmaturity patterns can be distinguished by their duration. Quantification may include assessment of interhemispheric synchrony in tracé alternante, typical of QS, or the counting of premature features such as delta brushes. Abnormalities of EEG patterns, noted in relation to sleep states and the instability of sleep-wake states during the newborn period, have some prognostic value. When different etiologies of the EEG pattern are considered, a few fundamental groups can be distinguished. Transient Metabolic Disorders Neonatal hypoglycemia can range from an asymptomatic state with a minimal EEG correlation to late-onset, idiopathic hypoglycemia accompanied by neurological symptoms and seizures. Toxemia and maternal diabetes are often encountered in high-risk pregnancies. These newborns usually present with decreased QS with a relative increase in AS. Transient hypocalcemia is often associated with barely abnormal interictal EEG and variable focal seizures (in 20% of patients). Inborn Errors of Metabolism Periodic EEG patterns in newborns with uneventful deliveries strongly suggest the possibility of an inborn error of metabolism. The most frequent neurological symptoms are early movement disorders, convulsions, and cognitive dysfunction. In 1977, Mises accurately described periodic EEG patterns in methylmalonic aminoacidopathy. High interindividual variability characterizes a pattern of periodic frontal or occipital sharp waves that are interspersed with rapid rhythms. In maple syrup urine disease, EEG complexes are low-voltage and less periodic; background activity is less depressed. Comb-like rhythms 40

41 during the second and third postnatal weeks are pathognomonic of this disorder. The highly peculiar EEG pattern of non-ketotic hyperglycemia distinguishes it from other forms. During the first 10 postnatal days, these infants, who present with hypotonia, respiratory distress, and myoclonic seizures, have EEGs characterized by periodic, highly stereotyped 1-3 Hz complexes with 4- to 18-second interburst intervals. Frontal, high-voltage slow waves are associated with characteristic rolandic and occipital early alpha rhythms. Pyridoxine dependence (not to be confused with pyridoxine deficiency) is inherited as an autosomal recessive trait and is accompanied by severely abnormal EEGs and refractory seizures that only respond to pyridoxal supplementation. CNS Infections An important distinction must be made between prenatal and postnatal infections. No specific or typical EEG patterns exist for the first group. Severity and extent of CNS involvement is more significant compared to noninfectious etiologies. Rubella and toxoplasmosis are the most common causative agents. Infants with congenital rubella and cataracts present with the most consistent EEG abnormalities in this group (i.e., prolonged subclinical seizures expressed as paroxysmal bursts without interburst intervals or alpha-like activity). In the occipital areas, there is marked asynchrony between burst and interburst intervals. Slow anterior dysrhythmia with excessive frontal sharp waves is present. Sleep states are not well defined, given the absence of recorded REM and the paucity of QS. Fetal toxoplasmosis is less disruptive, at least in terms of ultradian sleep cycle organization. It is associated with more variable EEG patterns. In cytomegalovirus, the EEG is frequently inactive. For postnatal infections (usually meningitis), the prognostic value of EEG is linked to the severity and extent of the abnormalities rather than their specificity. In most cases, they are associated with early status epilepticus (SE) or single seizures with a definite interval following birth that is unlike postanoxic SE. Consistently abnormal recordings (rather than merely an initial abnormal recording) are linked to an unfavorable prognosis. 41

42 Three distinctive patterns are associated with type 1 and type 2 herpes simplex virus (HSV) encephalitis. For pregnant women in many countries, HSV is still the most common (and preventable in neonates by means of cesarean section) genital infection. HSV is easily transmitted to the newborn during vaginal delivery. One type of EEG abnormality consists of continuous, sharply contoured unifocal or multifocal delta activity with a typical asynchronous distribution across several foci (each with a specific rate). Foci are predominantly temporal, frontal, or central in distribution. In older infants, hemispheric, monomorphic slow waves appear interspersed on a low-voltage or suppressed background. They may recur as periodic lateralized epileptiform discharges (PLEDs) within several seconds. Typical electroencephalographic seizures are associated with positive, multifocal sharp waves on a background that is characterized by significant interhemispheric voltage asymmetries and asynchrony. Focal Acute Neurological Abnormalities The following conditions may cause focal neurologic abnormalities: trauma, primary subarachnoid hemorrhage, intraventricular hemorrhage (IVH), intraparenchymal hemorrhage, and cerebral infarction. EEG abnormalities include an interhemispheric amplitude asymmetry pattern that is mainly seen with intraparenchymal hemorrhage or with a prenatal or postnatal ischemic insult. A wider criterion (>50%) is usually applied to preterm (PT) infants in whom significant hemispheric voltage alteration has been found to strongly correlate with contralateral hemiparesis. In 1984, Challamel reported that transient hemispheric asymmetries were a normal variant in infants with no CNS-related ailments who later resumed fully developed normal EEG patterns. The focal attenuation pattern refers to a single scalp region with a persistent voltage attenuation. This pattern has an inconsistent association with neuropathological lesions; both false-positive and falsenegative correlations have been observed. Focal slowing is highly unusual and may be a sign of ongoing seizures. Nonictal paroxysmal patterns include the following: Midline rhythmic bursts offer no diagnostic or prognostic clue when observed during non-rem sleep. These may represent the normal maturation ebouché of primitive sleep figures such as vertex waves. Positive rolandic sharp waves (PRWs), first described by Cukier in 1972 as pathognomonic of IVH, were considered poor prognostic indicators. Later studies by Tharp and Lombroso were not as conclusive about the long-term clinical implications. Although PRWs are seen in 30-50% of PT infants with IVH, they 42

43 also have been detected in infants with periventricular leukomalacia without hemorrhage as well as in intraparenchymal or subarachnoid bleeding. Therefore, PRWs are probably related to deep white matter lesions, although the underlying cause is still undetermined (see Picture 5). Positive temporal sharp waves (PTWs) are noted in the records of infants with hypoxic-ischemic damage and are thought to carry a poor prognosis. As with PRWs, the implications of the presence PTWs is still inconclusive. Although rarely associated with ictal discharges, occipital spikes/sharp waves, whether isolated or in unilateral brief runs, are usually found in a population of high-risk infants and considered to be abnormal regardless of age. Picture 5. Positive rolandic sharp waves R>L EEG in Neonatal Seizures Seizures frequently occur in newborns (14 per 1000), often causing death or permanent neurological sequelae. The prognosis largely depends on etiologic factors and the duration of convulsive activity. It should be noted that generalized tonic-clonic seizures are not seen in the immature brain. Seizure patterns can be distinguished into subtle, classic, tonic, and myoclonic types. Among these, some have a fairly consistent EEG 43

44 correlation. For example, tonic spasms, unlike those that occur in older children, are often associated with rhythmic delta wave activity. Clonic seizures frequently correspond to repetitive spike discharges. Myoclonic seizures, which are often erratic or fragmented and which should be distinguished from fragmentary neonatal sleep myoclonus, are often associated with other seizure types (e.g., tonic or clonic) and with a burst suppression pattern with or without ictal correlation. Ictal intervals, apnea, or respiratory disturbances often correlate with alpha like EEG patterns. These may be ictal discharges without clinical seizures that are not limited to iatrogenically paralyzed infants (see Picture 6, Picture 7, Picture 8, Picture 9). These occult or electrographic seizures without clinically detectable signs may result from iatrogenic loading, causing serious neurological injury that disables the effector structures or silent cortical areas, which might be more generalized in newborns than in older patients. Picture 6. Multifocal electrographic seizure in a curarized infant (alphalike pattern) 44

45 Picture 7. Same infant with L focal paroxysmal temporal discharges 45

46 Picture 8. Same infant with deltalike L-frontal electrographic seizure 46

47 Picture 9. Same infant. L electrographic seizure with multifocal L ictal discharges 47

48 Picture 10. Classic seizures corresponding to multifocal polyspike pattern with shifting predominance Conversely, clinical seizures in the absence of EEG discharges suggest nonepileptic events that should be closely monitored to avoid misdiagnosis. Minimal seizure behavior, uncoupled to ictal EEG patterns, can be seen in healthy neonates and especially in encephalopathic neonates whose brains are seriously compromised by hypoxic-ischemic insults. Severe neurological injury seen in these cases causes severe background EEG abnormalities. Several ictal discharge patterns have been identified and reported, including the following patterns: Focal spikes or sharp wave discharges of progressively increasing amplitude over the course of the seizure - These discharges correspond to contralateral jerking and occur predominantly in the rolandic and temporal regions. Multifocal spike and sharp wave discharges, which are often erratic with independent frequencies in multiple foci, are associated with variable seizure types. The underlying cause may range from benign conditions to CNS infection to various hypoxic-ischemic injuries. The prognosis is dependent on the background EEG abnormalities and the specific underlying etiology. Prehypsarrhythmic or hypsarrhythmic patterns can be seen early in compromised newborns, representing the most severe examples of the previous pattern, and are usually associated with 48

49 anarchic and refractory seizures. A separate group may be the brief ictal discharge pattern and questionable EEG ictal discharges. Decremental discharges, which sometimes accompany neonatal tonic seizures, must be distinguished from the normal arousal response that follows postural change or stimulation. Specific syndromes of neonatal seizures include the following: Early myoclonic encephalopathy (EME) was first proposed by Aicardi in 1978 to describe neonates who had myoclonic jerks and a burst-suppression EEG pattern. The main criteria include severe neurological abnormalities in otherwise healthy neonates with early fragmentary erratic myoclonia and a burst-suppression pattern. A microdysgenesic malformation or metabolic disorder may be discovered later. Early infantile epileptic encephalopathy (EIEE) was proposed by Otahara in 1976 and includes infants who, within 3 months after birth, develop refractory tonic spasm, developmental delay, and a burst-suppression EEG pattern. Most of these infants later develop a full-blown hypsarrhythmia in the context of West syndrome. Unlike EME, burst-suppression accompanies wakefulness as well as sleep. It is rarely familial but may be linked to cerebral malformations. Benign idiopathic neonatal convulsions (BINC), also known as fifth day convulsions, can be seen in both symptomatic and cryptogenic infants and are associated with a favorable outcome. BINC are associated with a specific EEG parameter (even with the variability of clinical manifestations) of alternating sharp-theta bursts that are observed in the interictal period. In 1966, Rett first described benign familial neonatal convulsions (BFNC), which are transmitted through autosomal dominant inheritance. The gene is localized on the long arm of chromosome 20 with regular penetration but variable expression. The incidence ( %) as well as the prevalence of epilepsy at later stages of life is low. EEG patterns are nonspecific. Neonatal pyridoxine dependency is defined by the empirical resolution of all symptoms with pyridoxine administration. The EEG pattern consists of repetitive runs of 1-4 Hz high-amplitude waves and spikes that are similar to the typical spike and wave discharges that are usually seen only in older children (see Picture 11). 49

50 Picture 11. Pyridoxine-dependent syndrome - generalized spikewave discharges Neonatal EEG as a Diagnostic and Prognostic Tool Although most neonatal EEG patterns are nonspecific and cannot provide the diagnosis when used alone, it is conversely true that they should cue the clinician to order neuroimaging tests. This is especially true for interhemispheric or regional asymmetries; specific EEG features may suggest infectious causes or deep matter necrosis, genetic brain malformations, or an inborn error of metabolism. EEG is also an excellent tool to help diagnose subclinical seizures or to avoid a misdiagnosis of seizures in the presence of atypical nonictal neonatal behaviors. When used selectively through serial recordings, neonatal EEG s greatest value is its potential for prediction of short- and long-term prognosis. The EEG background, static abnormalities, and EEG maturational indices are the best prognostic factors. Although some ictal discharges may have specific significance, a normal interictal EEG indicates the greatest chance of favorable outcome, even in the case of early, recurrent seizures. Several studies (e.g., those by Monod, 1972; Tharp, 1981; and Rose, 1970) have demonstrated the prognostic role of EEG in different diseases, ranging from neonatal seizures to asphyxia and hemorrhage. At this early developmental age, the EEG has a greater prognostic potential than any other diagnostic tool available to neonatologists. EEG is clearly 50

51 preferable to a neurological examination of a neonate who inherently displays a narrow behavioral and clinical profile. Prospectively, EEG can predict in early infancy later developmental patterns such as hypsarrhythmia with infantile spasms. References 1. Aicardi J, Goutieres F: Neonatal myoclonic encephalopathy (author s transl). Rev Encephalogr Neurophysiol Clin 1978; 8: Barlow JK, Holmes GL: Positive sharp waves: an electroencephalographic marker for recent hypoxia-ischemia in the neonate. Ann Neurol 1990; 28: Challamel MJ, Isnard H, Brunon AM, Revol M: Transitory EEG asymmetry at the start of quiet sleep in the newborn infant: 75 cases [transl]. Rev Electroencephalogr Neurophysiol Clin 1984; 14(1): Cukier F, André M, Monod N, Dreyfus-Brisac C.: Contribution of EEG to the diagnosis of intraventricular hemorrhages in the premature infant [transl]. Rev Electroencephalogr Neurophysiol Clin 1972; 2: Dreyfus-Brisac C, Flescher J, Plassert E: L electroencephalogramme: critére d age conceptionnel du nouveau né à terme et premature. Biol Neonate 1962; 4: Lombroso CT: Quantified electrographic scales on 10 pre-term healthy newborns followed up to weeks of conceptional age by serial polygraphic recordings. Electroencephalogr Clin Neurophysiol 1979 Apr; 46(4): Lombroso CT, Matsumiya Y: Stability in waking-sleep states in neonates as a predictor of long-term neurologic outcome. Pediatrics 1985 Jul; 76(1): Lombroso CT: Seizures in the newborn period. Handbook of Clinical Neurology 1976; 15: Lombroso CT: Neonatal seizures: a clinician s overview. Brain Dev 1996 Jan-Feb; 18(1): Lombroso CT: Prognosis in neonatal seizures. Adv Neurol 1983; 34: Mises J, Moussali F, Plouin F, Saudubray JM: An electroencephalographic study of disorders of amino-acid metabolism during the first days of life (author s transl).. Rev Electroencephalogr Neurophysiol 1977; 7: Monod N, Pajot N, Guidasci S: The neonatal EEG: statistical studies and prognostic value in full-term and pre-term babies. Electroencephalogr Clin Neurophysiol 1972 May; 32(5): Otahara S, Ishida T, Oka E: On the specific age-dependent epileptic syndrome. The early infantile epileptic encephalopathy with suppression-bursts. No To Attatsu (Tokyo) 1976; 8: Parmalee A, Schultz F, Akiyama Y: Maturation of EEG activity during sleep in premature infants. Electroencephalogr. Clin. Neurophysiol. 1968; 24: Plouin P: Benign neonatal convulsions. Neonatal Seizures 1990; Purpura D: Developmental pathobiology of cortical neurons in immature human brain. Intrauterine asphytia and the developing fetal brain 1977; Rett A, Teubel R: Neugeborenen in Rahme einer epileptisch belarten familie. Wein Klin Wschr 1964; 76:

52 18. Rose AL, Lombroso CT: A study of clinical, pathological, and electroencephalographic features in 137 full-term babies with a long-term followup. Pediatrics 1970 Mar; 45(3): Samson-Dollfus D: L EEG du premature jusqu à l age de 3 mois et du nouveau ne à terme. These Med Foulon 1955; Tharp BR: Neonatal Encephalography. Progress in Perinatal Neurology 1981; Trottier A, Metrakos K, Geoffroy G: A characteristic EEG finding in newborns with maple syrup urine disease (branched-chain Keto-aciduria). Electroencephalogr Clin Neurophysiol 1975; 38: 108 Improving Pediatric Polysomnography by Manisha B. Witmans, MD; Carole L. Marcus, MBBCh; Sally L. Ward, MD; and Thomas Keens, MD Overnight polysomnography is a highly specialized and technical study, considered the gold standard, for diagnosing sleep-disordered breathing (SDB) in children and adults. Differences in respiratory physiology and pathophysiology of SDB between children and adults make it difficult to extrapolate adult normative values to children. The American Thoracic Society (ATS) has published guidelines for performing and interpreting an overnight polysomnographic study in children; however, the changing technology has resulted in different nuances for identification of respiratory-related abnormalities during sleep that were previously not possible. In contrast to well-established normative data in adults for defining SDB, the limited normative data in children and adolescents are based on statistically defined values in small numbers. Nevertheless, there are some parameters for SDB in children that are consistent and should be used when interpreting sleep studies. The following article will briefly summarize what are generally accepted guidelines for defining SDB in children and adolescents. AMBULATORY TESTING The overnight polysomnogram is a cumbersome and expensive test, and efforts continue to establish alternative means of diagnosing SDB. Although there has been a great deal of interest in developing home ambulatory monitoring for diagnosing sleep disorders in children, there are few studies evaluating the efficacy of home-based testing for SDB. Pulse oximetry for screening SDB has been evaluated using different devices. Brouillette et al3 compared overnight oximetry studies to complete overnight polysomnogram studies in 349 children with suspected obstructive sleep apnea (OSA). Oximetry had a positive predictive value of 97% and a negative predictive value of 47%. The 52

53 results suggest that an oximetry study can identify children with SDB if the results are positive, but the test cannot rule out OSA. More recently, Kirk et al compared use of an oximetry-based home ambulatory testing device commonly used in adults to overnight polysomnography in 58 children (aged 4 to 18 years) with suspected OSA. The sensitivity and specificity were only 67% and 60%, respectively, for identifying moderate OSA (apnea-hypopnea index [AHI] >5 events/hour). Thus, oximetry testing alone is not sufficient for identifying SDB in children. Abbreviated testing using a limited sleep study or nap studies has also been shown to be helpful in identifying SDB. Marcus et al showed that nap studies using sedation have a sensitivity of 74% and a positive predictive value of 100%. In a larger subsequent study, none of the individual parameters evaluated in the nap studies were predictive of abnormal overnight polysomnograms in children with SDB. Overall, nap studies can be helpful in identifying children with SDB but often underestimate the severity of the problem. If the abbreviated test is not diagnostic, then the child or adolescent should still have further testing to definitively evaluate for SDB. OVERNIGHT POLYSOMNOGRAM The ideal setting for a pediatric overnight polysomnogram would be in an environment similar to the patient s home where the child or adolescent would feel comfortable and could sleep without difficulty. Similar to adults, preparation is essential to ensuring a successful overnight polysomnographic study. Environmental factors such as temperature, noise, bed size, and lighting control should be addressed. The child and adolescent should be adequately informed about the procedural details prior to the actual study date. Without such preparation, it is not uncommon to see either the child or parents overwhelmed by all the monitoring equipment. The patient should be at baseline status when the study is performed because even minor nasal congestion may result in overestimation of the severity of SDB. Sedation should not be used for inducing sleep in children because it can worsen airway obstruction and decrease the drive to breath, affecting the interpretation of the findings. The ATS has published consensus statements for optimal methods for collecting data. Biocalibrations should be done when feasible. The leads, electrodes, and sensors should be sized and placed in an age-appropriate fashion. For example, leads should be passed under the clothing and secured to minimize displacement, and leads involving the head and face should be secured last. 53

54 The ideal montage for polysomnography data collection should include all of the following: electroencephalography channels, preferably two or more leads, C3 or C4 and O1 or O2. electrooculography leads placed at 1.0 cm above and below the canthi chin electromyogram, leg electromyogram snore microphone respiratory airflow measurements oral thermistor/thermocouples and nasal pressure transducer chest and abdominal bands for respiratory effort or motion respiratory inductance plethysmography electrocardiogram pulse oximetry and pulse waveform (to differentiate true oxygen desaturation from motion artifact) end-tidal carbon dioxide monitoring (ETCO 2 ) sleep position notation Although esophageal pressure monitoring has been advocated for partial airway obstruction or upper airway resistance syndrome, these devices are not used by the majority of pediatric sleep laboratories in clinical settings Table 1. Definitions of respiratory events. Central apnea Simultaneous cessation of airflow (by thermistor/nasal pressure transducer and capnograph) and respiratory effort. Duration of >20 seconds is considered significant, or a shorter duration that is associated with oxygen desaturation or bradycardia. These can occur commonly after a sigh or body movement. Obstructive apnea Absence of airflow despite continued chest and abdominal wall efforts. The adult definition (>10 seconds duration) is considered inappropriate for use in children. Commonly used definitions include an apnea duration of two or more respiratory events. Mixed apnea Apneic events that include both central apnea and obstructed breaths. In adults, the obstructed component follows the central portion. Obstructive hypopnea (partial obstruction) Reduction in airflow; the degree of reduction has not been uniformly defined, but the AASM has published commonly used definitions.19 Most adult definitions include an arousal and/or accompanying oxygen desaturation. The AASM criteria have been adopted by the ATS and AASM to score hypopneas. 54

55 MEASURING UPPER AIRWAY OBSTRUCTION AND GAS EXCHANGE The method of measuring upper airway obstruction is not standardized across laboratories, especially in pediatrics, and may provide different results depending on the system used. Commonly used definitions are listed in Table 1. A pneumotachograph is the gold standard for obtaining airflow data; however, it is cumbersome and requires a tight-fitting mask, which is unlikely to be tolerated by children. Most pediatric sleep laboratories prefer to use indirect airflow measurement, which is usually performed in two ways: by thermistors using temperature changes between inspired and exhaled air or by exhaled ETCO 2 monitoring via side-stream capnography. The qualitative signal of thermistors provides limited information and can give inaccurate results if only nasal airflow is evaluated. Neither thermistors nor ETCO 2 monitoring is ideal for measuring hypopneas or partial upper airway obstruction because the signals are qualitative and subject to interpretation. More recently, nasal pressure airflow monitoring has been evaluated in infants and children and found to be a useful adjunct in the evaluation of upper airway obstruction. Nasal pressure monitoring is more linearly related to airflow, but is affected by mouth-breathing and secretions. In such circumstances, nasal pressure monitoring may overestimate the severity of SDB. ETCO 2 monitoring is critical for determining adequate gas exchange and should be measured during pediatric polysomnography.2 Obstructive hypopneas or partial airway obstruction may occur in the absence of oxygen desaturation or arousal from sleep, but can result in elevated ETCO 2. Furthermore, hypoventilation can go undetected without ETCO 2 monitoring. The sampling delay in signal recording from capnography can affect the interpretation of the signal and should be assessed. Newer devices are available for measuring both ETCO 2 and nasal pressure simultaneously. Oxygen saturation measurements should include pulse waveform recording to differentiate true oxygen desaturation from motion artifact. In addition, the rapid averaging time is preferred during overnight polysomnography to capture discrete reductions in the oxygen saturation that may be missed using longer averaging times. Transcutaneous monitoring of oxygen and carbon dioxide can be used as adjuncts to measuring gas exchange. A good waveform is needed to have reliable carbon dioxide data. The monitoring can be helpful for identifying trends, but has slower response times relative to the respiratory event, even with optimal skin perfusion. NORMAL POLYSOMNOGRAPHIC VALUES Only two studies have prospectively evaluated normal respiratory reference values during overnight polysomnography in healthy children and adolescents. The data were interpreted according to published 55

56 guidelines.1 Only healthy children without symptoms of OSA were included. Exclusion criteria were obesity, airway abnormalities, any airway surgery, craniofacial anomalies, or associated lung disease. Despite some differences between the two studies, there are many similarities in the findings (Table 2). Table 2. Normative data for respiratory events. Age Range Obstructive Apnea Central Apnea AHÍ ETCO 2 Pulse Oximetry 1-16 years <1 event per hour <1.5 events Abnormal Maximum Value Normal Nadir (n=50) per >45 mm 53 mm Hg 96 2% 92% hour Hg (n=41) >60% of total sleep time (TST); or >50 mm Hg for >10% of 11 months to 18 years (n=70) <1.2 events per hour <1 per hour TST >45 mm Hg for >10% of TST 50 mm Hg % 92% Central apneas can occur during sleep, more commonly in rapid eye movement sleep. Transitional central apneas are also common. Children can have central apneas after sighs or movement arousals lasting as long as seconds, without associated oxygen desaturation. Based on the findings, only central apneas associated with desaturation, arousal, or bradycardia are considered significant, irrespective of the duration. Most laboratories score central apneas >20 seconds duration, unless following motion or sigh. In contrast to central apneas, obstructive apneas are uncommon in children. The pathophysiology of SDB in children includes a spectrum of airway obstruction, ranging from episodic partial airway obstruction to complete airway obstruction. In contrast, adults have less partial airway obstruction. Furthermore, in children, the partial airway obstructions may not result in arousals despite obvious changes in ventilation. Obstructive apneas are often scored differently in adults compared to children. The adult scoring criterion is >10 seconds per event; however, other studies showed that apneas were short (<10 seconds and <13 seconds, respectively). Similar data were obtained in older adolescents. None of the studies cited duration of apnea based on age. Many centers use two 56

57 respiratory cycles to calculate duration of the apnea because younger children have faster respiratory rates and adult-based criteria, may be inappropriate. Both studies 15,16 found that an AHI greater than 1.2 events per hour is more than two standard deviations above normal. In contrast, adult reference values list >5 obstructive apneas per hour of sleep as abnormal. The controversy exists for adolescents because there are no specific normative data for this age group to know when pediatric or adult norms should be used to make the diagnosis of SDB. Hypopneas are respiratory events with a reduction in airflow, but not all laboratories score these respiratory events using the same criteria in children. The American Academy of Sleep Medicine (AASM) has published consensus definitions for scoring hypopneas in adults. The two definitions that are suggested include an abnormal respiratory event lasting >10 seconds with a 50% decline in baseline airflow amplitude, or an abnormal respiratory event lasting >10 seconds with a smaller reduction in airflow amplitude, but with an associated arousal or desaturation. There are virtually no normative data in children for obstructive hypopneas. The initial study by Marcus et al did not include hypopneas because a standard definition for hypopnea did not exist at the time of the publication. The original data by Marcus et al were reviewed recently (N=41 of the initial 50 children) for obstructive hypopnea. Obstructive hypopnea was defined as a decrease in airflow to less than 50% baseline amplitude for a minimum of two respiratory cycles. Desaturations (>3%) and arousals were scored if present, but were not required to identify the hypopnea. Six children had any hypopneas, mean duration 12.8 seconds (range ). One child had associated arousals with the hypopneas and two children had desaturations of 3%. The mean obstructive hypopnea index was 0.1 ± 0.1 (range ) events per hour. Using the AASM definitions did not change the results. The statistically significant AHI in healthy children is therefore 1.5 events per hour (mean ±2 SD). The results show that obstructive hypopneas are uncommon in healthy children, similar to results in older adolescents. The limitation is that these data are based on outdated technology, and normative data using current technology (nasal pressure monitoring) are needed; however, the data contribute to the spectrum of what is considered normal. One of the discrepancies between the two normative data studies was the ETCO 2 capnography cut points. Both studies used only parameters with good waveforms. A possible explanation for the differences may be related to the type of capnometer used to collect data. The differences reiterate the paucity of data in pediatric polysomnography. In conclusion, there are data published related to pediatric polysomnography and these provide an important reference guide for 57

58 scoring respiratory parameters in children and adolescents. Although there are no population-based studies to help define clinically significant cut points in children, these data are still useful for identifying abnormalities during pediatric polysomnography. Normative data using newer technology are desperately needed to establish accurate diagnostic and clinically significant endpoints to aid in diagnosis and treatment, hence to prevent morbidity and mortality associated with SDB in children. REFERENCES 1. American Thoracic Society. Standards and indications for cardiopulmonary sleep studies in children. Am J Resp Crit Care Med. 1996;53: American Thoracic Society. Cardiorespiratory sleep studies in children. Establishment of normative data and polysomnographic predictors of morbidity. Am J Respir Crit Care Med. 1999;160: Brouillette RT, Morielli A, Leimanis A, Waters KA, Luciano R, Ducharme FM. Nocturnal pulse oximetry as an abbreviated testing modality for pediatric obstructive sleep apnea. Pediatrics. 2000;105: Kirk VG, Bohn SG, Flemons WW, Remmers JE. Comparison of home oximetry monitoring with laboratory polysomnography in children. Chest. 2003;124: Jacob SV, Morielli A, Morgrass MA, et al. Home testing for pediatric obstructive sleep apnea syndrome secondary to adenotonsillar hypertrophy. Pediatr Pulmonol. 1995;20: Marcus CL, Keens TG, Ward SLD. Comparison of nap and overnight polysomnography in children. Pediatr Pulmonol. 1992;13: Saeed MM, Keens TG, Stabile MW, Bolokowicz J, Davidson Ward SL. Should children with suspected obstructive sleep apnea and normal nap studies have overnight sleep studies? Chest. 2000;118: Guilleminault C, Winkle R, Korobkin R, Simmons B. Children and nocturnal snoring: evaluation of the effects of sleep related respiratory resistive load and daytime functioning. Eur J Pediatr. 1982;139: Guilleminault C, Poyares D. Arousal and UAR. Sleep Medicine. 2002;3:S15-S Trang H, Leske V, Gaultier C. Use of nasal cannula for detecting sleep apneas and hypopneas in infants and children. Am J Respir Crit Care Med. 2002;166: Witmans MB, Bohn S, Kirk VG. Reliability of nasal pressure recording during pediatric polysomnography. Am J Crit Care Med. 2003;167:A American Academy of Pediatrics. Clinical practice guidelines: diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. 2002;109: American Academy of Pediatrics. Technical report: diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. 2002;109: Witmans MB, Marcus CL, Keens TG, Ward SL. Normal polysomnographic values for obstructive hypopneas in infants and children. Sleep. 2003;26:A

59 15. Marcus CL, Omlin KJ, Basinki DJ, et al. Normal polysomnographic values for children and adolescents. Am Rev Respir Dis. 1992;146: Uliel S, Tauman R, Greenfield M, Sivan Y. Normal polysomnographic respiratory values in children and adolescents. Chest. 2004;125: Rosen CL, D Andrea L, Haddad GG. Adult criteria for obstructive sleep apnea do not identify children with serious obstruction. Am Rev Respir Dis. 1992;146: Meoli AL, Casey KR, Clark RW, et al. Clinical Practice Review Committee. Hypopnea in sleep-disordered breathing in adults. Sleep. 2001;24: American Academy of Sleep Medicine Task Force. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep 1999;22: Witmans MB, Keens TG, Ward SL, Marcus CL. Obstructive hypopneas in children and adolescents: normal values. Am J Respir Crit Care Med. 2003;168: Acebo C, Millman RP, Rosenberg C, et al. Sleep, breathing, and cephalometrics in older children and young adults. Part I: normative values. Chest. 1996;109: Uliel S, Tauman R, Greenfield M, Sivan Y. Normal polysomnographic values for children and adolescents. Am J Respir Crit Care Med. 2002;165:262A. Sleep and Disorders in Children The first modern description of obstructive sleep apnea hypoventilation syndrome (OSAHS) in children dates from 1976, in a report of eight children presenting with snoring and variable daytime symptoms including headache and somnolence. Like obstructive sleep apnea (OSA) in adults, childhood OSAHS is characterized by recurrent episodes of partial or complete airway obstruction during sleep, often accompanied by oxyhemoglobin desaturation or hypercarbia. Unlike adults, however, children are more likely to exhibit periods of prolonged partial airway obstruction rather than discrete events such as apneas and hypopneas. Prolonged partial airway obstruction sometimes takes the form of obstructive hypoventilation, in which pulmonary ventilation falls below the level necessary to maintain normocapnea, even when normal oxygen saturation is maintained. Upper airway resistance syndrome (UARS), in which abnormally high upper airway resistance leads to increased respiratory effort and disrupted sleep even in the absence of gas exchange abnormalities, has also been described in children. It is estimated that between 10 and 12% of children snore habitually and that between 1 and 3% of children suffer from OSAHS. The prevalence of UARS in children remains unknown. Obstructive sleep apnea hypoventilation syndrome may present at any age during childhood, with peak incidence between 2 and 5 years of age, when adenotonsillar hyperplasia is most common. [78] Prevalence of OSAHS is equal in boys and girls until adolescence, when a male preponderance becomes 59

60 strikingly evident. Obesity is less strongly associated with OSAHS in children than in adults. Craniofacial abnormalities (e.g., cleft palate, choanal atresia, macroglossia) may be associated with increased risk of OSAHS. Other genetic and neurological conditions may also be associated with increased risk, most notably Down syndrome, in which at least one-third of children are affected. The clinical features of OSAHS in children overlap only partially with those exhibited by adults (Table 2). Snoring is almost universal in affected children. Other common nighttime symptoms include prominent mouth breathing, unusual sleeping positions, excessive perspiration, and refractory enuresis. Symptoms upon waking often include transient grogginess, headache, or sore throat. In contrast to adults, however, daytime somnolence is seldom a prominent complaint. When present, somnolence is often intermittent or tends to occur during sedentary activities such as reading or riding in an automobile. Many recent reports support the premise that even childhood sleep-related breathing disorders (SRBDs) of mild severity may be associated with attentional, behavioral, and learning problems. Habitual snoring has been reported to be three times as frequent in children with ADHD compared with control groups drawn from child psychiatry and general pediatrics clinics. [84] In a study of 297 first-grade children with poor academic achievement, 54 (18.1%) exhibited either significant hypoxemia or hypercapnia during limited overnight monitoring. Of these, the 24 children treated with adenotonsillectomy exhibited significant academic improvement (P < 0.01) compared with the untreated children. Physical examination of children with SRBDs is often normal. Tonsillar hypertrophy, although common, is neither necessary nor sufficient for the diagnosis of SRBDs. Adenoid facies (long face syndrome), daytime mouth breathing, or micrognathia may be apparent. Elevated blood pressure may be occasionally evident in affected children. Because full polysomnography in children is both costly and time-consuming, inexpensive and easily administered screening measures have long been sought. Screening tests such as home audiotapes and overnight oximetry have demonstrated only limited sensitivity for detection of SRBDs in children. A recently developed Pediatric Sleep Questionnaire has demonstrated sensitivity of 0.81 to 0.85 and specificity of 0.87 for the prediction of SRBDs in a clinical research environment but has not been validated for use outside this setting. Polysomnography in children monitors at minimum the same respiratory, cardiac, and neurophysiological data measured in adult PSGs. End-tidal or transcutaneous CO 2 monitoring is sometimes added to augment the sensitivity of the study when hypoventilation is suspected (Fig. 2). Esophageal pressure monitoring may be used selectively when increased upper airway resistance or prolonged partial airway obstruction is 60

61 suspected. Interpretation of the pediatric polysomnogram differs from that of adults. Although scoring of sleep stages and arousals is performed in the manner used for adult studies, there exist no universally accepted pediatric standards for the scoring and interpretation of respiratory disturbances. Some centers score apnea according to adult criteria, which typically require a minimum duration of 10 seconds. Other centers score apneas that exceed the length of two respiratory cycles, which is often less than 10 seconds due to the high respiratory rates seen normally in young children. In addition, there is no consensus on the definition of hypopnea in children. 61