In this 1 hour and 2‑minute video, Dr. Jessica Duis, an Associate Professor of Pediatrics and Genetics at Children’s Hospital Colorado, University of Colorado, will highlight presentations of sleep disorders in PWS, diagnostic evaluation, and treatment considerations.
Click below to watch the video. If you're short on time, scroll down for timestamps to find the portions you're most interested in.
Presentation Summary With Timestamps
Dr. Jessica Duis presents: Presentations and Management of Sleep Disorders in Prader-Willi Syndrome
0:06 Introduction of Dr. Duis by Kristen White
- Dr. Duis is a pediatric geneticist and special care pediatrician.
- She did her medical training at Johns Hopkins School of Medicine in Baltimore, and completed a postdoctoral fellowship in the Johns Hopkins Department of Psychiatry and Behavioral Sciences.
- She is a board certified pediatrician and medical geneticist who practices in the area of genetics and specialty care pediatrics.
- She primarily performs diagnostic workups and management for individuals with rare disorders.
- She focuses on neurogenetic conditions and rare genetic causes of obesity and metabolic conditions.
- She’s passionate about establishing standards of care, developing objective and sensitive outcome measures, and improving clinical trial design for individuals with neurodevelopmental disorders to improve quality of life and equity of care.
1:15 Learning Objectives
- Utilize case-based learning to discuss presentations of sleep disorders in PWS.
- Consider diagnostic evaluation.
- Consider presentations that masquerade as other manifestations of PWS.
- Review treatment strategies for sleep disorders in PWS.
2:27 Case 1: 10-Year-Old with PWS and Daytime Sleepiness
- This young male with PWS falls asleep at school.
- If he is awakened, he is irritable and can escalate behaviors quickly and become aggressive.
- He is quick to get frustrated and angry, sometimes around food.
- Sometimes triggers are around food, other times they are unclear.
- He will sleep anywhere, especially on car rides.
3:00 Excessive Daytime Sleepiness
- Decreased wakefulness with an increased percentage of sleep time and stage N3 sleep during the day and night.
- Maybe be part of the initial clinical phenotype at birth when individuals with PWS are excessively sleepy and often fall asleep during feeding.
- 67% of adults report EDS
- May be confounded by obstructive sleep apnea (OSA)
- Commonly presents with irritability and behavioral disturbances
- If someone is having frequent awakenings at night, sometimes it can be difficult to characterize what excessive daytime sleepiness is because the common thought is that you have to get the OSA 100% controlled before you can understand if somebody really has excessive daytime sleepiness.
- If someone has excessive daytime sleepiness they may be in a deeper state of sleep when they get disturbed, and that is really confusing and can lead to outbursts and a lot of discomfort in general.
- They can be more snappy and irritable.
- Emphasizes that one of the masquerading symptoms in PWS for excessive daytime sleepiness is school performance.
5:38 Excessive Daytime Sleepiness and School
- Excessive daytime sleepiness could be associated with problems with attention or behavioral disturbances at school.
- EDS disrupts school performance.
- Keep in mind: 10 hours of sleep is recommended for school-age kids; 9 hours for adolescents.
- That’s continuous, “good” sleep, which if you have OSA, you have problems with sleep efficiency.
- Need to pay attention to sleep hygiene:
- Establish bedtime routine.
- Get rid of blue light in room.
- Watch for drug interference.
- Circadian rhythm disruptions, especially in Schaaf-Yang syndrome.
- Sound machine should stay on all night.
- Medical conditions can also affect sleep: diabetes, frequent urination, movement disorders, parasomnia, restless leg syndrome.
- Behavioral disorders also affect sleep.
- Insomnia can send people foraging for food.
- Increased sleep drive can contribute to excessive daytime sleepiness.
- Narcolepsy, or a modified version of narcolepsy is something that can play a part.
- In the real world, we can never fully get rid of OSA. It’s important to educate providers about that because often they will be resistant to other diagnoses because they first want to think about 100% compliance with a CPAP or completely getting sleep apnea under control
9:44 Diagnosing EDS
- Gold standard for diagnosis of excessive daytime sleepiness and narcolepsy is sometimes called a multiple sleep latency test.
- Overnight, you’ll have a sleep study and then in the morning when the flights are on, they have the individual sit and see how long it takes them to fall asleep and how long they sleep.
- There are certain criteria for diagnosis of EDS vs. narcolepsy.
10:10 Treatment of EDS in PWS
- Encourage providers to treat EDS even if they are having OSA. These medications have been shown to help.
- Modafinil, a narcolepsy drug, can be helpful to decrease sleepiness.
- Clomipramine reduced EDS in an 11-year-old with PWS.
- Tryptophan reduced EDS in an 8-year-old with PWS.
- Pitolisant: growing body of evidence that this drug targets the histamine receptor and promotes wakefulness. May also improve cognitive function and ability to focus.
- PWS community has had some success getting insurance to cover Pitolisant, and there is a clinical trial about to enter phase 3.
12:39 Case 2
- An 8-year-old with PWS with recent excessive weight gain presents with irritability, excessive sleepiness, increased food seeking, including awakening and foraging for food at night, worsening school performance, and headaches.
- Parents have noted more snoring, especially when she is ill.
- Weight increase is well above the 97th percentile; really took a turn at age 8.
13:18 Obstructive Sleep Apnea
- Between 60 and 80% of individuals with PWS have OSA.
- 90% of people with PWS will have OSA at some point in their life.
- More than 80% of individuals with PWS exhibit sleep disordered breathing, including OSA.
- Percentile of BMI for the individuals’ age and sex has been associated with more severe hypoxemia during sleep and more sleep disruptions.
- Untreated OSA has been associated with more severely delayed developmental milestones.
- Worsening OSA has also been associated with EDS and ADHD with worsening impulsivity.
- Behavioral changes should prompt concern for worsening OSA. Developmental milestones may be more severely delayed in individuals with untreated OSA.
- We should look at general school performance and attention because it can be related to OSA.
16:18 Diagnostic Work Up for OSA
- Diagnosis of OSA is via polysomnography.
- Drug-induced endoscopy should be performed when an infant is diagnosed with OSA prior to the development of tonsils and adenoids.
- The camera allows us to see if there are reasons like flopping over the epiglottis that would give a surgical option to treat the OSA.
- In infants, it’s hard to get them to use a CPAP, so oftentimes we’ll use oxygen.
- In general, treatment is:
- Referral to otolaryngology (GNT)
- Oxygen for hypoxemia and sometimes if adherence to other treatments is low.
- CPAP
- Behavioral therapy with desensitizations to assist in use of CPA should be considered upon initiation of therapy.
- In the case of mild OSA, a trial of intranasal fluticasone with or without montelukast can be used as an alternative to CPAP.
- In cases where PAP therapy fails, consider Optiflow nasal high flow therapy (NHF)
18:34 Growth Hormone (GH) and OSA
- Current recommendations on the label for use of growth hormone is to get a sleep study before you initiate growth hormone and while continuing GH therapy.
- Obtaining a PSG should not delay initiation of GH therapy .
- Approximately 10 weeks after initiating GH, a follow-up sleep study may be needed to check for worsening symptoms (snoring, witnessed apnea, daytime sleepiness) or signs such as weight gain.
- Findings of worsening OSA (OAHI) should expedite evaluations and treatment but not stop or delay GH treatment.
- Clinical management of patients on GH who are diagnosed with OSA remains highly variable among endocrinologists and sleep specialists.
- The following conditions warrant a referral for PSG:
- Snoring
- Witnesses apneas
- Rapid weight gain
- Change in school performance
- New onset attention concerns
- Worsening EDS
- More irritability or changes in behavior
- Lack of progression in development
- Routine PSG should be performed at age 3 and at the onset of puberty.
23:00 Case 3:
- Newborn infant in the NICU is noted to have apneic events, followed by bradycardia. She is noted to have low muscle tone and poor interest in feeding. Testing for PWS is pending.
23:10 Central Sleep Apnea
- Signal to the brain for your body to breathe is not working properly.
- In a sleep study, the apnea occurs after you see a drop in the oxygen below the threshold.
- The CO2 actually goes up in this case. No respiratory effort.
- Absence of breathing, and don’t see ventilatory response.
- 3 types of apnea:
- Obstructive: tongue flops back in the throat or there is excess tissue or the adenoids are big and obstruct the flow of air in the airway.
- Central: No air flow and no respiratory effort.
- Mixed: some of both.
24:55 Screening and Treating CSA
- Continued monitoring with frequent PSGs approximately every 6 months for individuals with central adrenal insufficiency.
- Supplemental oxygen has been shown to be an effective treatment for infants and is the therapy of choice for this age group.
- For older individuals, CPAP is the standard of care.
25:47 Case 4
- 6-year-old with a history of concerns for seizures (ruled out with EEG in the past) described as loss of tone during eating.
- More recently, she has been falling asleep, sometimes midsentence.
- School is concerned about recent changes in her performance.
- If she is awakened at school, she gets very angry and emotional.
- After seeming to regain her energy, she falls immediately back asleep after an emotional outburst.
- Recent sleep study shows mild OSA; ENT recommended flonase.
- Her level of sleepiness is out of proportion to her mild OSA.
- Parents came to clinic concerned about regression due to seizures.
27:09 Narcolepsy and Cataplexy: Presenting Features
- Narcolepsy
- Children can have profound baseline facial hypotonia and some patients experience motor tics.
- Automatic behavior (repetitive and common behaviors at night)
- Disrupted nighttime sleep.
- Obesity is common in children with narcolepsy; more than half of children who present with signs of narcolepsy are obese
- Approximately one-third of children with narcolepsy also have symptoms of ADHD or behavior concerns.
- Cataplexy
- May resemble clonic, atonic, and/or myoclonic seizures. Loss of consciousness is absent with cataplexy.
- Loss of tone and/or complex hyperkinetic movements.
- Facial involvement that may include active movement of the tongue and perioral muscles.
- Children may experience cataplexy without a clear emotional trigger.
- Cataplexy or sudden onset of atonia provoked by emotion appears relatively commonly in PWS: head drops in young children as they eat solid food is an example.
- Consensus statement on work up for narcolepsy/cataplexy:
- “Since a diagnosis of narcolepsy also requires that a patient’s EDS is not caused by insufficient sleep or another sleep disorder, such as OSA, it can be difficult to obtain a formal diagnosis of narcolepsy in PWS. Often patients with PWS and OSA have difficulty adhering to their prescribed positive airway pressure (mainly CPAP or bilevel positive airway pressure (BPAP) therapy). This means that, per clinical guidelines, OSA cannot be excluded as a cause of their excessive daytime sleepiness. This situation may contribute to the underdiagnosis of narcolepsy in the PWS population. Because EDS is often out of proportion to OSA, we recommend that screening for narcolepsy type features should be undertaken in individuals with PWS despite residual OSA.”
30:55 Treatment of Narcolepsy in PWS
- Amphetamine/methylphenidate
- Modafinil
- Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants may be used to treat cataplexy.
- Sodium oxybate, the sodium salt of gamma hydroxybutyrate
- Pitolisant
- Cautions: Amphetamines or stimulants are not good treatments for cataplexy; they’re more for EDS and you have to be really careful with SSRIs and PWS because if you titrate the dose too high it can activate them or cause more behaviors or aggression.
33:33 Other Disorders to Be Aware of IN PWS
- Chronic Insomnia:
- Consider food-seeking, behavioral concerns, anxiety or perseverative behaviors that could be impacting sleep.
- Referral to sleep specialist.
- Consider behavioral therapy.
- Improve food security in the home to decrease anxiety and access.
- Restless leg syndrome:
- Recent Cochrane review found that iron supplementation likely improves restlessness and restless leg syndrome in comparison to placebo. Benefits were seen even when participants did not have low blood levels of iron.
- Consider checking serum ferritin.
- With iron therapy, consider risks of constipation and monitor ferritin to ensure appropriate dosing. Also ensure iron is stored safely in a locked cabinet in the home as acute overdose may be fatal.
35:11 Symptoms to Consider as Possibly Related to Sleep Disorders in PWS
- Neurobehavioral:
- Behavioral concerns (irritability, impulsivity, outbursts, rigidity, inability to reason, anxiety, depression)
- Slow processing speed, poor focus, inattention
- Motor and balance concerns
- Physical Health:
- Poor feeding
- Growth delay
- Food seeking
- Daily Living:
- Poor school performance
- Fatigue and daytime sleepiness
- Poor stamina
36:07 Recommendations
- Consider how growth hormones affect sleep.
- Educate providers about the indications for sleep studies.
- Watch for irritability, change in school performance, or anything that would prompt you to think about another sleep study.
- Do sleep studies regularly, every few years.
- Sleep problems that are out of proportion to OSA are really important to watch for.
- Start thinking about some of these treatments; they can be life-changing for some of these kids.
37:27 Q & A
