Hypoventilation and Apnea in Prader-Willi Syndrome

(Last updated on June 29, 2007)

Note: This article is a work-in-progress and still somewhat incomplete. Feedback would be very welcome, so please feel free to e-mail me with any comments you might have.

Table of contents

• Introduction
• Important updates
• Definitions
• Effects of chronic hypoxia and chronic intermittent hypoxia
• Impaired respiratory function in PWS
• Obstructive sleep apnea (OSA)
• Risk factors for obstructive sleep apnea
• Obstructive sleep apnea and failure to thrive in infants
• Polysomnography
• Tips for child sleep studies
• Paradoxical inspiratory rib-cage movement and upper airway resistance syndrome
• Polysomnography and growth hormone treatment in PWS
• Treatment of breathing disorders in PWS
• Additional resources

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Introduction

The purpose of this article is to assist health care providers, parents and other caretakers of those with Prader-Willi Syndrome (PWS) in understanding the critical importance of early diagnosis and treatment of the hypoventilation and sleep apnea which are very common in PWS. It is my sense that hypoventilation, sleep apnea, and obstructive sleep apnea are under-diagnosed in those with PWS and, as a result, a potentially significant part of the mental and physical lethargy, low activity levels, hypersomnia, excessive daytime sleepiness and drowsiness, failure to thrive in infancy, impaired growth and developmental delays, behavioral disturbances and/or cognitive impairment typically associated with PWS may actually be at least in part caused by the oxidative stress and other effects of chronic intermittent hypoxia due to the weak respiratory function and sleep apnea that are characteristic of PWS. Health care providers need to be vigilant about the high possibility of impaired respiratory function in PWS and the negative effects of hypoventilation and apnea in PWS should be aggressively addressed through both direct treatment (for example, with continuous positive airway pressure (CPAP) for obstructive sleep apnea or night-time supplementary oxygen for hypoventilation) and indirect amelioration of the oxidative stress caused by hypoxia, for example, by the use of anti-oxidants.

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Important updates

• A November 16, 2006 medical journal article by Camfferman et al has added considerable weight to the argument that untreated sleep-related breathing disorders play a potentially significant part in the cognitive impairment and behavior disturbances that are considered characteristic of PWS. Indeed, the Camfferman article is so important that it is worth including the full abstract here:

• A September 2006 study (Festen et al) found that "a relatively normal PSG [polysomnography] does not exclude the possibility of unexpected death during mild URTI [upper respiratory tract infection]" in infants and young children with PWS and made the important recommendation that "cardiorespiratory monitoring during URTI in children with PWS before and during GH-treatment should be considered." In addition, some PWS experts in the U.S. are now recommending that (1) parents of infants and young children with PWS should have a home pulse oximetry device available in order to monitor blood oxygen levels during even mild URTIs such as colds, and (2) the temporary stopping of growth hormone treatment during respiratory infections. Note, however, that the abrupt ending of growth hormone treatment can disrupt glucose homeostasis and precipitate an acute hypoglycemic crisis, as discussed in this PWS Dots Journal article.

• On June 25, 2007, another study by Festen and colleagues of 22 infants (1.1-3.4 years) found that all had sleep-related breathing disorders, mostly of central origin. In addition, the four infants who had obstructive sleep apnea had significantly delayed mental development of 65.5% (range - 60.0-70.3%) of normal, leading the researchers to suggest that all infants with PWS should be screened for obstructive sleep apnea.

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Definitions

First, some definitions for those not familiar with the relevant respiratory and sleep-related terminology.

• Breathing is the process by which oxygen (which is critical for energy metabolism throughout the body) is brought into the body and the carbon dioxide (CO2) created through the burning (oxidation) of glucose and fatty acids for energy is expelled.
• Hypoxia (hypoxemia) is a deficiency of oxygen reaching the tissues of the body. The brain's normal response to hypoxia is react with signals to breathe, but those with PWS often have a severely impaired response to hypoxia.
• Blood oxygen saturation (SaO2) is a measure of the amount of oxygen being carried by the blood. Normal SaO2 is 95% to 100%.
• Hypercapnia refers to an elevated level of carbon dioxide in the blood. Normally the brain reacts to hypercapnia with signals to breathe, but those with PWS often have an impaired (if not totally absent) response to hypercapnia. The normal range for blood CO2 partial pressure is 35-45 mm Hg and levels over that are a key indication of hypoventilation. When CO2 levels are increased during a significant part of the night, the excess CO2 can remain in the body even during waking hours and cause problems with behavior, moods, the ability to focus, and memory.
• Hypoventilation is breathing that is not adequate to meet the needs of the body because it is too shallow or too slow and is common in PWS. Hypoventilation can occur in the absence of apnea and hypopnea and results in inadequate oxygenation of the blood and/or a rise in carbon dioxide levels in the blood.
• Apnea is a transient cessation of breathing.
• Sleep apnea is a condition characterized by episodes of breathing cessation during sleep. There are three basic types of sleep apnea - central sleep apnea (CSA), obstructive sleep apnea (OSA), and mixed sleep apnea.
  • Central sleep apnea (CSA) occurs when the brain fails to send the signal to the muscles to take a breath. Central sleep apnea is common in those with PWS
  • Obstructive sleep apnea (OSA) occurs when the brain sends the signal to breathe to the muscles and the muscles try to take a breath but are unsuccessful because the airway is blocked. Obstructive sleep apnea is also common in those with PWS. (There's more on OSA below.)
  • In mixed or complex sleep apnea, there is both CSA and OSA. Mixed sleep apnea is common in PWS.
• In adults, an apnea event is usually defined as an episode of apnea that lasts at least 10 seconds, but some define it instead as any drop in oxygen saturation levels (SaO2) of 4% or more. In children, apnea lasting more than three to six seconds or for the length of one and one-half to two breaths is considered significant. (There's more on apnea events below.)
• Hypopnea is defined as an event in which airflow decreases by 50 percent for at least 10 seconds or decreases by 30 percent if there is an associated decrease in SaO2 or an arousal from sleep and is usually caused by a partial obstruction of the airway.
• Polysomnography is a night-time test of breathing and sleep cycles and stages through the use of continuous recordings of brain waves (EEG), electrical activity of muscles, eye movement (electrooculogram), breathing rate, blood pressure, blood oxygen saturation (SaO2), heart rhythm, and direct observation of the person during sleep.
• The Apnea-Hypopnea Index (AHI) is used to grade the severity of sleep apnea and hypopnea and is based on the average number of apnea and hypopnea events per hour during polysomnography. In adults, an AHI of less than 5 is considered normal, 5-15 is mild sleep apnea, 15-30 is moderate sleep apnea, and more than 30 events per hour is considered severe sleep apnea. In children, an AHI greater than 1 is abnormal and severe is greater than 20. It is not uncommon to see AHIs well above 40 and in some cases even above 100, with events lasting as long as 90 to 120 seconds and SaO2 going below 70%.

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Effects of chronic hypoxia and chronic intermittent hypoxia

Chronic hypoxia and chronic intermittent hypoxia cause a huge cascade of responses throughout the body as it attempts to adapt to low oxygen conditions by increasing the efficiency of energy-producing pathways (mainly by switching to anaerobic glycolysis) and decreasing energy-consuming processes such as protein synthesis. The responses include changes in protein, fat and glucose metabolism, immune system functioning, neurotransmitter transport, cellular (mitochondrial) functioning, and gene expression, and have been associated with the following conditions and physiological effects:

• excessive daytime sleepiness and hypersomnia in both children and adults (Halbower 2006, O'Donoghue 2005, Zhan 2005a, Zhan 2005b, Melendres 2004, Veasey 2004, Gottlieb 2003, Chervin 2002, Brouillette 1982)
• "failure to thrive" in infants (Bonuck 2006, Freezer 1995, Leiberman 1988, Brouillette 1982)
• reduced growth hormone releasing hormone, growth hormone, IGF-1 and IGF-binding protein-3 levels (Feng 2006, Nieminen 2002, Chiba 1998, Chanoine 1998, Cooper 1995, Grunstein 1989) (there also may be impaired end-organ response to growth hormone due to chronic acidosis from chronic hypercapnia)
• poor growth (Halbower 2006, Bonuck 2006, Greene 1997)
• developmental delays (Leiberman 1988, Brouillette 1982)
• anorexia (Yingzhong 2006)
• neuropsychological dysfunctions such as learning and memory impairment, decreased attention, and poor school performance, including deficits in verbal working memory and verbal fluency, problem solving, and the ability to adapt to new situations (Halbower 2006, Mulvaney 2006, Rosen 2004, Gottlieb 2004, Archbold 2004, Gottlieb 2003, Naegele 1998, Greene 1997, Bedard 1993)
• an average 15-point decrease in IQ in children with severe OSA (Halbower 2006)
• ADHD-like behavior (Halbower 2006, Rosen 2004, Melendres 2004, Huang 2004, Gottlieb 2003, O'Brien 2003, Chervin 2002)
• in children with PWS, autistic-like behavior (O'Donoghue 2005)
• increased emotional lability, aggression, impulsivity and oppositionalism in children (Halbower 2006, Mulvaney 2006, O'Donoghue 2005, Rosen 2004, Gottlieb 2003)
• increased obsessive-compulsiveness, depression, anxiety, and hostility (Yue 2003)
• impaired thyroid and other endocrinal functioning (Bratel 1999)
• impaired sexual development and decreased pituitary-gonadal secretion (hypogonadism) (Luboshitzky 2003, Luboshitzky 2002, Mosko 1980)
• increase in cell-damaging reactive oxygen species (ROS - free radicals) (Halbower 2006, Zhan 2005a, Veasey 2004, Xu 2004, Morita 1995)
• reduced cerebral blood flow and altered cerebrovascular responses to hypercapnia (Halbower 2006)
• abnormal morphology of the frontal cortex, cerebellum, and hippocampus, including ventriculomegaly (Halbower 2006, Ment 1998)
• indications of neuronal injury, including in the frontal cortex and especially in the cerebellum and hippocampus (Halbower 2006, Xu 2004)
• changes in metabolites in the brain similar to those seen in diseases in which there is brain cell damage (Halbower 2006, Xu 2004)
• increased proinflammatory responses (Zhan 2005a, Zhan 2005b)
• reduction in the extent of myelination in the corpus callosum (Kanaan 2006)
• substantial alterations in gene expression (294 genes upregulated and 440 genes downregulated), including a significant reduction in the expression of genes important in growth and development and an increase in leptin gene expression (Iacobas 2006, Fan 2005, Grosfeld 2002, Ambrosini 2002, Chavez 2000, Zelzer 1998)
• high cholesterol and impaired cardiovascular functioning, including cor pulmonale (Halbower 2006, Li 2005, Greene 1997, Morita 1995)
• decreased pancreatic polypeptide levels (which are also reduced in PWS) (Jennum 1989)
• reduced serum adiponectin (Zhang 2004)

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Impaired respiratory function in PWS

As evidenced by the studies cited below, impaired respiratory function, especially during sleep, in almost all of those with PWS is well-documented. Indeed, given the near universality of sleep-related breathing disorders in those with PWS and the severe impacts of chronic intermittent hypoxia and hypoventilation, my feeling is that a polysomnography (PSG) should be performed as soon as possible after the diagnosis of PWS has been made.

• Priano 2006, in polysomnographs of of 18 young adults with genetically confirmed PWS, found that although only four had an Apnea-Hypopnea index (AHI) equal to or greater than 10, significant nocturnal oxygen desaturation occurred in 83% independent from apnea or hypopnea events.
• Festen 2006, in a study of 53 normal-weight pre-pubertal children with PWS, found that all of the children had an AHI that exceeded the normal range of 0-1 per hour; the median AHI was 5.1, with a range of 2.8 - 8.7/hr.
• O'Donoghue 2005, in a study of 13 subjects with PWS (age 1.5 to 28 years), found that nine (69%) had more than 10 apneas and hypopneas per hour of sleep, including a 2-year-old with normal body weight who demonstrated severe central hypopnea during rapid eye movement (REM) sleep.
• Harris 1996, in a study of eight PWS patients, found that sleep-disordered breathing occurred in all and was principally characterized by obstructive hypoventilation or episodes of apnea that occurred primarily during rapid eye movement (REM) sleep. After significant weight loss, sleep-disorder breathing parameters only improved in three of the subjects.
• Schluter 1997, in a polysomnography study of eight PWS patients (five boys, three girls, aged 6 weeks-12.5 years) compared with controls matched for gestational age, sex, birth weight and age, found that the PWS group had an increased number of apnea events per hour of sleep, decreased nadir of oxygen saturation, increased maximum of the instantaneous heart rate and decreased respiratory responses to hypercapnia (high carbon dioxide blood levels) during quiet sleep.
• Gozal 1994, in a study of peripheral chemoreceptor function during wakefulness in 17 genetically confirmed PWS patients and 17 matched controls, concluded that those with PWS have absent peripheral chemoreceptor ventilatory responses and speculated that the lack of ventilatory responses is due to primary peripheral chemoreceptor dysfunction and/or defective afferent pathways to central controllers.
• Arens 1996, in a study of the arousal response to hypoxia during sleep in 13 patients with PWS and 11 matched controls, found that only one of the patients with PWS was aroused by the hypoxic challenge; heart rate only increased by 9 +/- 2% in the PWS group versus 22 +/- 4% in the controls; respiratory rate did not change in the PWS group (4 +/- 2%) but increased by 13 +/- 2% in the controls; and concluded that abnormal arousal and cardiorespiratory responses to hypoxia are frequent in PWS.
• Livingston 1995, in a study of arousal response to hypercapnic challenge during stage 3/4 non-REM sleep in ten nonobese children and adults with PWS, and nine controls, found that the PWS subjects had a significantly higher arousal threshold to hypercapnia compared with the controls (53 +/- 1.0 vs 46 +/- 1.7 mm Hg) and had more central apneas, and concluded that elevated hypercapnic arousal thresholds during sleep are found in PWS and may be a manifestation of abnormal peripheral chemoreceptor function.
• Clift 1994, in a study of 17 children and young adults with PWS and excessive daytime sleepiness, found a high respiratory event index with frequent brief apneas, particularly in REM sleep, in 16 subjects, and most of the apnea events were not accompanied by arousal.
• Richards 1994, in a study of 14 subjects with PWS, found that 12 had sleep apnea (AHI greater than 10 events per hour).
• Smith 1998 noted that daytime respiratory failure due to hypercapnia is a common cause of death in PWS and reported significant improvement in arterial blood gas parameters in four patients treated with continuous positive airway pressure (CPAP).
• Arens 1994, in a study of rebreathing hypercapnic and hypoxic ventilatory responses (HCVR and HPVR, respectively) during awakefulness in both obese and non-obese PWS patients and obese and non-obese controls, found that the response to hypercapnia was significantly lower in obese PWS patients than in obese controls.
  • In PWS patients, the mean point of origin of the positive slope of HCVR occurred at a significantly higher end-tidal PCO2 than in either control group.
  • During isocapnic hypoxic challenges, six PWS patients had no significant HPVR and in the remainder, mean slopes of HPVR were -0.80 +/- 0.06 l.min-1.%arterial O2 saturation-1 in five non-obese PWS patients and -0.68 +/- 0.15 l.min-1.%arterial O2 saturation-1 in six obese PWS patients responses that were significantly decreased compared with the controls.
  • Summary: non-obese PWS patients have normal HCVR, which is blunted in obese PWS patients, and isocapnic HPVR is either absent or markedly reduced in PWS patients, with the severity of HPVR abnormality being independent of the degree of obesity.

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Obstructive sleep apnea (OSA)

First a bit of necessary anatomy: The genioglossus muscle comprises much of the body of the tongue and is attached to the inside front of the jawbone (see illustration). With normal muscle tone, the genioglossus holds the tongue forward in the mouth when one is awake and is the muscle used to stick one's tongue out. In at least some infants with PWS (and perhaps other ages), poor muscle tone results in the tongue not staying forward even when when the infant is awake and alert.

When the body takes a breath, the chest expands and the diaphragm lowers, creating a vacuum that pulls in air through the airway. In obstructive apnea, that vacuum can pull the soft palate, tongue and uvula (the little tear-shaped thing that hangs down from the back of the throat) against the back of the throat, blocking the airway, especially when the airway is narrow as is common in PWS. In addition, most of the body's muscles relax during non-REM (rapid eye movement) sleep and in REM sleep, the muscles completely relax, including the genioglossus. When that happens, the tongue can fall back (especially if the person is sleeping on their back) and block the airway, resulting in obstructive apnea.

An obstructive sleep apnea event has four stages:

• First, the airway becomes blocked.
• Second, an effort is made to take a breath, but is unsuccessful due to the blocked airway.
• Third, with the body unable to inhale, a drop in blood oxygen saturation levels (SaO2) occurs along with an increase in the blood's carbon dioxide (CO2) levels (hypercapnia). When SaO2 drops, the heart starts pumping harder in order to move more blood with each beat. As the SaO2 continues to drop, the heart also starts beating faster. As CO2 increases, the brain sends increasingly strong signals to increase the effort and action of the abdomen and chest, but that only increases the vacuum and causes the blockage to seal tighter. In other words, in order to breathe, the person must awaken (arouse) enough to reactivate the muscles and soft tissues around the airway, including the genioglossus so that the tongue moves forward, thereby opening the airway and allowing air to pass into the lungs.
• Fourth, the efforts of the chest and diaphragm muscles finally become so strong that they cause the person to arouse enough that the genioglossus and other airway muscles and tissues contract, clearing the airway so that a breath can be taken. Such arousals are often only partial (e.g., from deep sleep (stages 3, 4, or REM) to a shallow level of sleep) and are typically unrecognized, even if they occur hundreds of times a night. The person then falls back into full sleep, the tongue and soft tissues again relax, and the whole process gets repeated.

So there are two very bad things going on in sleep apnea:

• One, a drop in the amount of oxygen getting to the brain and other body tissues (hypoxia) and a rise in CO2 levels (hypercapnia). In severe apnea, SaO2 can drop to 70% and even less (normal is 95% to 100%).
• Two, a fragmentation of sleep, particularly deep sleep. Sleep is not restful, so those with sleep apnea typically have fatigue, excessive daytime sleepiness and drowsiness and hypersomnolence. In severe obstructive sleep apnea, very little time is spent in deep sleep and the result is severe sleep deprivation regardless of how many hours are spent in the lighter sleep stages.

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Risk factors for obstructive sleep apnea

Those with decreased muscle tone (hypotonia), increased soft tissue around the airway (e.g., enlarged tonsils and adenoids), a narrow airway and snoring are at high risk for obstructive sleep apnea, which puts those with PWS right in the middle of the ballpark for OSA. Certain facial dysmorphias, such as a small lower jaw, are also risk factors for OSA, since they reduce the amount of room in the mouth for the tongue, thus serving to push the tongue back towards the throat and soft palate. Interestingly, African-Americans have a 2.5 times greater risk of obstructive sleep apnea than whites.

In adults, the primary symptoms of OSA are snoring, not breathing while asleep, excessive daytime sleepiness and obesity. Other symptoms include lack of concentration, forgetfulness, irritability, anxiety, depression, mood and/or behavioral changes, morning headaches, disorientation at awakening, and loss of sexual interest.

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Obstructive sleep apnea and failure to thrive in infants

Obstructive sleep apnea in adults is often associated with obesity, but infants and young children with chronic sleep apnea are more likely to be thin and may even have failure to thrive (FTT). An eMedicine article on pediatric obstructive sleep apnea notes that, "Indeed, reports from the early 1980s found more than a 50% prevalence of FTT in patients with pediatric OSA." The poor growth occurs for numerous reasons, including: (1) the work of breathing is high enough that calories are burned at high rates even at rest or sleep, (2) the same obstruction that occurs during OSA can also happen during feeding, thereby interfering with adequate food intake (dysphagia), (3) diminished or altered patterns of nocturnal growth hormone secretion due to the chronic intermittent hypoxia (reduced SaO2) that results from OSA, and (4) a reduction in appetite as one of the body's adaptive responses to chronic intermittent hypoxia (indeed, one researcher has seriously proposed high altitude-related hypoxia as a treatment for obesity).

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Polysomnography

It is my (nonprofessional) opinion that a polysomnography (PSG) should be performed for all infants and children promptly after the diagnosis of PWS has been made. Because sleep-related breathing disorders tend to present much more subtly in infants and young children than in adults, they can be difficult to diagnose even after a polysomnography and some experts feel that any child presenting with snoring and daytime sleepiness or lethargy should be treated even when a polysomnography is supposedly negative because the effects of sleep-related breathing disorders can be so serious in terms of physical and cognitive development. I am not usually an advocate of aggressive western-style medical treatment, but in this case I agree that, for example, a trial of supplemental oxygen or continuous positive airway pressure (CPAP) during night-time sleep should be seriously considered for infants and young children with PWS who present with hypotonia, borderline or frank failure to thrive, hypersomnolence (over-sleeping), mental and physical lethargy, developmental delays, and/or behavioral disturbances, even in light of a negative polysomnography.

An important issue to be aware of regarding polysomnography is the significant variability that can occur among different sleep labs in how polysomnographs are scored. For example, Suzuki 2005 studied the inter-scorer reliability among 16 sleep labs by having them score the polysomnography for an adult male and found only 23.5% agreement in identifying slow wave (deep) sleep, 59.8% agreement for Stage 1 sleep, 73.2% for wakefulness and 74.2% for Stage 2 sleep; rapid eye movement (REM) sleep was the most reliably identified stage (91.3%). Overall, the median rate of inter-scorer coincidence for all sleep stages was only 71.8%. The apnea index (AI) varied from 1.3 to 6.5 events per hour; the hypopnea index (HI) ranged from 10.5 to 26.5 events per hour; and the apnea-hypopnea index (AHI) ranged from 13.5 to 29.5 events per hour. Similar differences were found in the scoring of the number and length of desaturation events and arousals. The variability among the labs was primarily related to the different definitions and methods of detection used to identify different sleep stages and breathing events such as apneas and hypopneas. There is also a trend towards the use of computerized polysomnography scoring systems, but their accuracy is likewise governed by the algorithms used to identify sleep stages and detect breathing abnormalities and arousals, particularly in infants and young children.

It is essential that polysomnography for infants and children include monitoring of carbon dioxide levels, as elevated CO₂ levels for a significant portion of sleep are a key indication of hypoventilation, which can occur in the absence of apneas and hypopneas. Sleep labs that usually cater to adults often do not monitor CO₂ levels, so make a point make sure beforehand that CO₂ levels will be monitored.

It is important to note that a low AHI does not mean that everything is okay. For example, Mikami 1999 reported on "four patients with mild obstructive sleep apnea syndrome (OSAS) with frequent breathing-related electroencephalogram (EEG) arousals which led to excessive daytime sleepiness. In spite of a relatively low apnea hypopnea index (AHI), sleep was disrupted by frequent EEG arousals associated with respiratory effort as observed in upper airway resistance syndrome. ... We consider that AHI alone is not a sufficient index to assess severity of OSAS, and it is very important to examine microarousals by the alteration of esophageal pressure in addition to the effect of sleep position."

The following is an indication of the types of questions I would ask when discussing the results of a polysomnography, particularly if it is deemed negative:

• What was the Apnea Index (AI)?
  • What is their definition of an apnea event in infants or children?
• What was the Hypopnea Index (HI)
  • What is their definition of an hypopnea event in infants or children?
• What was the Apnea-Hypopnea Index (AHI)? If greater than 1 -
  • What was the mix of apnea vs. hypopnea?
• Were there any signs of obstructive sleep apnea? If so -
  • How long was the average event?
  • How long was the longest event?
  • Did SaO2 levels ever drop below 95%? If so -
    • how low did the desaturations go?
    • what was the average SaO2 during an event?
    • what was the average length of desaturation events?
    • how much time in total was spent at a SaO2 less than 95%?
• Were there any signs of central sleep apnea? If so -
  • How long was the average event?
  • How long was the longest event?
  • Did SaO2 levels ever drop below 95%? If so -
    • how low did the desaturations go?
    • what was the average SaO2 during an event?
    • what was the average length of desaturation events?
    • how much time in total was spent at a SaO2 less than 95%?
• Were there any signs of mixed (complex) sleep apnea? If so -
  • What was the pattern (e.g., CSA followed by OSA)?
  • How long was the average event?
  • How long was the longest event?
  • Did SaO2 levels ever drop below 95%? If so -
    • how low did the desaturations go?
    • what was the average SaO2 during an event?
    • what was the average length of desaturation events?
    • how much time in total was spent at a SaO2 less than 95%?

If it is reported that there were no signs of sleep apnea, I would ask:

• What is their definition of an apnea event in infants or children?
• What is their definition of an hypopnea event in infants or children?
• Were there any signs of hypoventilation, e.g., did SaO2 levels ever drop below 95%? If so -

how low did the desaturations go?

• what was the average SaO2 during a hypoventilatory event?
• what was the average length of desaturation events?
• how much time in total was spent at a SaO2 less than 95%?

• Was the sleep stage pattern (i.e., pattern of progression through wakefulness, stages I through IV, and REM sleep and the length of time spent in each) normal compared to the relevant age group?
• Were there any indications of sleep fragmentation, particularly fragmentation of deep sleep?
• What was the total number of arousals per hour?
  • What was the average number of non-apneic arousals per hour?
• Were there any signs of "paradoxical inspiratory rib-cage movements" or "upper airway resistance syndrome" (see below)?
  • Were there frequent EEG microarousals associated with respiratory effort as is observed in upper airway resistance syndrome?

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Tips for child sleep studies

• Have the sleep technician hook up all of the sensors before the child goes to sleep (I know of at least one infant's PSG that was botched because the tech said to let her go to sleep first, but then the baby woke up while the sensors were being attached and never went back to sleep again).
• If a CPAP test is going to be performed during the PSG, make sure beforehand that they have an appropriately sized mask (for example, one of the most highly regarded pediatric sleep study programs in Los Angeles didn't have a mask small enough for a 9-month-old).
• If a CPAP test is going to be done during the PSG, try to get a mask several weeks ahead of time so that you can desensitize the child to it beforehand because many infants and small children will react with terror to the sense of breath claustrophobia caused by a mask, which is exacerbated when the CPAP machine is turned on because of the strong air flow. Start out with brief periods of playing with the mask, such as putting on yourself, a teddy bear or doll and then the child, and try to work up to where the child will tolerate wearing the mask for at least several minutes. If you can't get a CPAP mask, you might instead try using a filter mask like those available at Home Depot, etc. Also, try to get the child used to the sensation of a pretty strong air stream against their face by blowing on them, starting with gentle puffs and working up to strong blowing, especially around their nose. You might also try something like directing the air from a small aquarium air pump around their face. Do NOT point the airflow directly at the eyes, though!

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Paradoxical inspiratory rib-cage movement and upper airway resistance syndrome

The following excerpt from Pediatric Obstructive Sleep Apnea (from the Baylor College of Medicine web site) may help give a better sense of pediatric polysomnography findings:

Obstructive Sleep Apnea In Pediatric Patients (also from the Baylor College of Medicine web site) describes "paradoxical inspiratory rib-cage movement" as follows:

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Polysomnography and growth hormone treatment in PWS

As discussed more fully in the article about growth hormone treatment for PWS, excessive growth hormone is associated with thickening of the pharyngeal wall and is believed to be the cause of the increase in sleep apnea, both obstructive and central, that is common in conditions with supranormal growth hormone levels such as acromegaly. There is therefore a theoretical possibility that growth hormone treatment in children might cause an increase in the size of the adenoids, tonsils, and other airway tissues, thereby increasing the risk of obstructive sleep apnea, but so far no studies have specifically addressed that issue. This is a particular concern in PWS because those with PWS often have pharyngeal narrowing. A polysomnography prior to beginning growth hormone treatment and periodically during the course of GH treatment is therefore recommended for those with PWS.

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Treatment of breathing disorders in PWS

There are a variety of treatments available for sleep-related breathing disorders, including continuous positive airway pressure (CPAP) and dental appliances to help keep the tongue forward in the mouth during sleep for obstructive sleep apnea and supplementary oxygen via nasal cannulae during sleep for hypoventilation. The question of which treatment is best for any given individual is far beyond the scope of this article and should be discussed with your health care providers.

Research has demonstrated that some nutritional supplements with anti-oxidant properties, such coenzyme Q10 and l-carnitine and acetyl-l-carnitine, effectively ameliorate at least some of the damage caused by chronic hypoxia and chronic intermittent hypoxia; indeed, I suspect that at least some of the benefit that CoQ10 and carnitine have shown in some of those with PWS may come from their ability to relieve the oxidative stress caused by chronic hypoxia.

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Additional resources

In addition to the excellent eMedicine article cited above, Medicinenet and Wikipedia have good articles on sleep apnea in general. Other good resources include:

• eMedicine: Pediatric Sleep Apnea
• Medscape Pediatrics: Sleep-Related Breathing Disorders in Children
• American Thoracic Society, Standards and indications for cardiopulmonary sleep studies in children (1995)
• Sleep Review: Pediatric Polysomnography
• Sleep Review: Improving Pediatric Polysomnography
• Infant Polysomnography Comes of Age (article)
• Apnea Support Forum - Pediatric Sleep Apnea
• Apnea Support Forum - Sleep Studies - Post your child's sleep study and get feedback.
• Pediatric Obstructive Apnea Sleep Syndrome