Sleep and Smith-Magenis Syndrome
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1 Sleep and Smith-Magenis Syndrome Beth Malow, MD, MS Professor of Neurology and Pediatrics Burry Chair in Cognitive Childhood Development Director, Vanderbilt Sleep Disorders Division and Vanderbilt Sleep Core
2 Presentation Goals ü To describe the features of sleep problems in Smith-Magenis Syndrome ü To discuss how we study sleep patterns and identify causes we can treat ü To review treatments to help sleep, including both behavioral and medication-related
3 Developmental Conditions with Prominent Sleep Disturbances Insomnia Hypersomnia ü Autism Spectrum Disorder ü Rett syndrome* ü Angelman Syndrome* ü Prader-Willi syndrome ü Smith-Magenis syndrome* ü Fragile X syndrome ü Williams syndrome* ü Down syndrome ü Epilepsy *severe, persistent, difficult- to- treat insomnia is included in the diagnos7c criteria
4 What is Insomnia? repeated difficulty with sleep initiation, duration, consolidation, or quality that occurs despite ageappropriate time and opportunity for sleep and results in daytime functional impairment for the child and/or family (Mindell et al, 2006) ü Prolonged time to fall asleep ü Decreased sleep duration ü Increased arousals and awakenings Causes include ü Biological- melatonin/clock genes ü A medical/psychiatric disorder or medication is causing insomnia (sleep apnea, ADHD, stimulant) ü Poor sleep habits
5 What is Hypersomnia? a disorder characterized by excessive daytime sleepiness Causes include ü Not enough sleep ü Sleep is disrupted by a medical condition during the night (sleep apnea, seizures, pain) ü A medication is causing sleepiness (drugs to treat seizures) ü A brain disorder is causing sleepiness (narcolepsy) ü Biological/genetic consequences (melatonin secretion during the day)
6 What are the Possible Causes of Sleep Disturbance in SMS? Melatonin Regula7on Circadian Clock Factors Biological Medical Behavioral
7 Smith-Magenis Syndrome: Sleep and Melatonin Ø Decreased sleep, frequent and prolonged night wakings, early morning waking, and daytime sleepiness. Inverted melatonin pattern. Gropman A et al, Current Opinion in Neurology, 2007
8 24-hour day and sleep behavior in a child with SMS De Leersnyder H, J Pediatics, 2001
9 Melatonin Synthesis and Metabolism B-blockers X Tryptophan serotonin AA-NAT N-acetylserotonin ASMT Melatonin 6-sulfoxymelatonin CYP1A2 (major metabolite) Brzezinski A, NEJM, 1997
10 What are the Possible Causes of Sleep Disturbance in SMS? Melatonin Abnormali7es Circadian Clock Factors Biological ADHD Seizures Sleep Apnea Medical Behavioral
11 Obstructive Sleep Apnea Common in general pediatric population (2-6%) and important to treat (cardiopulmonary, ADHD symptoms) Diagnosis based on history alone can be challenging ü Adenotonsillar hypertrophy ü Obesity ü Allergic rhinitis ü Craniofacial abnormalities ü (cleft lip/palate, midface hypoplasia) Often multifactorial!
12 Zaremba, Barkey, Mesa, Sanniti, Rosen. Making polysomnography more "child friendly:" a familycentered care approach. J Clin Sleep Med, 2005 Polysomnography
13 Actigraphy Ø Actigraphy is a promising technique for measuring sleep patterns and responses to treatment in children, especially those with neurodevelopmental disorders (AASM, 2007) Ø Commercially available, wireless, non-intrusive, relatively inexpensive, and amenable to weeks of data collection Ac7watch (Philips Respironics) Pocket placement (Souders, 2009; Adkins, 2012) AMI device
14 What are the Possible Causes of Sleep Disturbance in SMS? Melatonin Deficiency Circadian Clock Factors Biological ADHD Seizures Sleep Apnea (midface hypoplasia, obesity, and cler lip/palate contribute) Medical Behavioral Poor Sleep Habits Sensory Issues Stereotyped Behavior
15 Components of Successful Sleep (for any child) Day7me habits Sleep environment Evening habits Bed7me rou7nes Sleep Hygiene Sleep hygiene is a term used to describe a person s day6me and evening habits that contribute to successful sleep.
16 Components of Successful Sleep (for any child) Day8me habits Exercise Abundant light Limit caffeine Limit naps Selec7ve bedroom use
17 Components of Successful Sleep (for any child) Evening habits Limit s7mula7ng ac7vi7es Less light Rou7nes Avoid ea7ng at night
18 Components of Successful Sleep (for any child) Sleep Environment Temperature Texture Sound Light
19 Measuring Sleep Hygiene The Family Inventory of Sleep Habits We developed this sleep habits questionnaire for use in our research It contains 12 questions that ask about sleep habits in the child and family Excellent test-retest reliability and external validity with the Children s Sleep Habits Questionnaire (CSHQ) Malow et al, Child Neurol, 2009
20 Time for bed q Put on pajamas q Use the bathroom q Wash hands q Brush teeth q Get a drink q Read a book q Get in bed and go to sleep Line Drawings Checklist
21 Strategies for Night Wakings The first step to minimizing night wakings is to help your child fall asleep on his/her own A child who can fall asleep on his/her own can go back to sleep alone Watch out for items that the child becomes dependent on to fall asleep that may not be there when the child wakes up.
22 Respond quickly to distress Comfort and reassure yet remember brief and boring. Yet avoid over- responding Use visual reminders. Choose realis7c goals. Rewards Strategies for Night Wakings
23 Strategies for Co-sleeping and Night Wakings The Rocking Chair Method Let your child fall asleep on his/her own but stay in the room, sicng in the rocking chair, with your back to your child Move the chair closer to the door each night un7l you are out of the door Rewards: Morning s8ckers or basket of presents.
24 Pharmacological Treatment Ø Best used after behavioral treatments have been tried unsuccessfully, and in combination with behavioral therapies Ø Whenever possible, choose a medication that will treat a comorbidity such as epilepsy, anxiety, or a mood disorder Ø Start at low doses, especially in children with developmental disorders (less able to communicate adverse effects effectively) Ø For primary insomnia, no FDA-approved drugs. We have reported success and minimal adverse effects in autism with melatonin (Andersen, J Child Neurol, 2008) and gabapentin (Robinson, J Child Neurol, 2013). Ø Extended release melatonin (Circadin) showed promise in openlabel compassionate use program for children with neurodevelopmental disorders, the majority with SMS
25 Pharmacological Treatment
26 Pharmacological Treatment Ø Extended release melatonin minitablet preparations (Circadin, Neurim Pharmaceuticals) and melatonin agonists (Tasimelteon, Vanda Pharmaceuticals) are under study. Ø Other options clinicians use include clonidine, mirtazapine, niaprazine, zolpidem, zaleplon, ramelteon, and respiridone. None of these has been tested in definitive trials, and side effect profile is important. Ø Be careful of children being so sedated that they are not able to fall asleep on their own. For hypersomnia Ø B-blockers to decrease melatonin secretion during the day Ø Modafinil (Provigil) or armodafinil (Nuvigil)
27 Summary Sleep disorders are common in children with SMS Sleep disorders are treatable Identification of sleep disorders can contribute to improved health and quality of life Overnight sleep studies (polysomnography) are needed to diagnose sleep apnea and seizure activity Actigraphy may be more appropriate for measuring sleep patterns in cases of insomnia and daytime napping Sleep education should be tried as a first line treatment or in combination with medications Medication options, particularly for insomnia, are under intensive study Thank you!
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