1 Sleep & Developmental Disabilities: Lessons for All Children March 28, 2012 Lawrence W. Brown, MD Pediatric Neuropsychiatry Program Sleep Disorders Center The Children s Hospital of Philadelphia 2 Importance of Sleep Intrinsic scientific interest Reflection of brain development Significant behavioral consequences Relevance to neurological disorders 3 Sleep - Definition A reversible behavioral state of perceptual disengagement from and unresponsiveness to the environment Unlike coma, a physiologic, recurrent, and reversible condition A complex amalgam of physiological and behavioral processes
4 How do doctors study sleep? Polysomnography Multiple Sleep Latency Test Actigraphy 5 Polysomnography Sleep staging (EEG, eye leads, muscle leads) Airflow (nasal & oral) EKG Chest and abdominal wall motion End-tidal CO 2 Oxygen saturation Video 6 Multiple Sleep Latency Test Semi-quantitative test of daytime sleepiness 4-5 nap opportunities throughout the day Patients asked to try to fall asleep in bed in darkened room every 2 hrs 20 min opportunity to fall asleep; 15 minutes of recorded sleep Norms available above 6 yrs old
7 Actigraphy Accelerometer worn on wrist that measures body movement Correlates to wakefulness and sleep (including non-rem vs REM) Device can be worn for weeks; much more accurate than sleep diary 8 Idealized Sleep Histogram 9 Idealized Sleep Histogram Note stage 3-4 non-rem sleep
10 Idealized Sleep Histogram Note REM sleep 11 Normal Sleep in Infants Term infant - 16-18 hrs sleep 3-4 hr cycle throughout day Increasing day wakefulness and night sleep by 1 month 6 month mean sleep 14.2 hrs 6-8 hours of continuous night sleep most common 6-9 months - increased nocturnal awakenings 12 Normal Sleep in Toddlers Gradual decline in total sleep time From mean of 13.9 hrs at 1 yr to 11.4 hrs at 5 yrs 1-2 naps/day totaling 2-4 hrs Frequent short naps or long late afternoon nap may interfere with night sleep Most children give up daytime nap by age 3 Sleep problems in 20-40% Good sleepers awaken as often as poor sleepers
13 Normal Sleep in Older Children Decline in total sleep time From mean of 11.1 hrs at 5 yrs to 10.2 hrs at 9 yrs Typical ideal sleep/wake schedule No difficulty in falling asleep Least likely to need alarm clock Optimal daytime alertness (mean MSLT=19 min) 14 Normal Sleep in Adolescents Further decline in total sleep From mean of 9.0 hrs at 13 yrs to 7.9 hrs at 16 yrs Sleep architecture maturation 40% decline in SWS; slightly more stage 2 NREM; stable REM Increased daytime sleepiness Present even if total sleep stable Tendency to delayed sleep and waking 15 Common Pediatric Sleep Problems Infant Poor consolidation of sleep-wake cycle Difficulty settling Toddler Behavioral disorders Non-REM parasomnias Obstructive sleep apnea
16 Behavioral Sleep Disorders in Early Childhood Sleep-onset associations Unstructured or inconsistent routine Highly stimulating bedtime activities Night fears, anxiety Acute illness Activating medications Neurological disabilities *Settling problems: 20% of 1-3 yr olds and 10% of 4 yr olds 17 Graded Approach to Sleep Resistance Common sense Consistent sleep schedule Regular bedtime routine Avoidance of overly stimulating activity Must first distinguish behavioral sleep disorder from medical conditions such as apnea, reflux Structured behavioral interventions from graduated extinction ( Ferberizing ) to limiting bedtime hours Medication only as last resort 18 Non-REM Parasomnias Sleep walking, sleep talking, agitated arousals, sleep terrors Typically first 1/3 of night (1-4 hrs) Worse with sleep deprivation, stress Difficulty in arousing child from event Little or no recall of event Must be distinguished from seizures Family history in 60%
19 Treating Non-REM Parasomnias Reassurance Environment safeguards Scheduled awakenings Only evidenced-based non-drug treatment Awaken child 15-30 minutes before expected event Effective in 50% Low dose benzodiazepines Clonazepam, diazepam 20 Other Common Pediatric Parasomnias Rhythmic movement disorder Head banging, body rocking REM sleep disorders (nightmares) Most often in last 1/3 of night Occur in >50% of 5-7 yr olds Enuresis 15% at 6 yrs with 15% resolution per yr (which still leaves 2% at 13 yrs) 21 Apnea: Definition Apnea: absence of airflow at the nose/mouth Obstructive apnea: No airflow despite respiratory effort (due to airway obstruction) Central apnea: No airflow or respiratory effort (often due to CNS dysfunction)
22 Obstructive Sleep Apnea: Nocturnal Signs Noisy respirations and loud snoring Observed apnea, gasping, choking Restless sleep Night sweats Enuresis 23 Obstructive Sleep Apnea: Daytime Signs Morning headache, dry mouth Overactivity Attention problems Learning difficulties Irritability Aggression Fatigue 24 Treating Obstructive Sleep Apnea Tonsillectomy & Adenoidectomy Continuous Positive Airway Pressure Weight loss Other surgery Palatal reconstruction Craniofacial repair Tracheostomy
25 Common Pediatric Sleep Problems Older Child Insomnia Obstructive sleep apnea Sleep schedule disorders Daytime sleepiness Periodic limb movements of sleep 26 Periodic Limb Movements of Sleep and Restless Legs Syndrome PLMS: Brief, repeated jerks of extremities during sleep every 0.5-5 sec, cycle every 5-90 seconds Often seen with Restless Legs Syndrome in adults, but children rarely complain Desire to move extremities, usually associated with discomfort and motor restlessness Relief by movement Increased in evening and during periods of rest/ inactivity 27 Evaluating PLMS in Children Usually presents as insomnia or growing pains Family history - positive in >70% Serum ferritin as indication of iron depletion Consider renal failure, diabetes, thyroid function studies, B12, folate, EMG/ Nerve conduction studies
28 Treating PLMS and RLS Avoid drugs that may aggravate symptoms Antihistamines, neuroleptics, SSRIs Iron therapy for low ferritin (<50 mcg/l) or iron saturation < 16% Medications Dopaminergic agents (pramipexole, ropinirole) Other drugs (clonazepam, clonidine, gabapentin) 29 Common Pediatric Sleep Problems Adolescent Insomnia Daytime sleepiness including inadequate sleep, delayed sleep phase syndrome, narcolepsy 30 Insomnia in Adolescents Inadequate sleep time and poor sleep hygiene Late bedtime, irregular sleep schedule, availability of multiple electronic devices, caffeine All compounded by increasing autonomy Natural tendency toward delayed sleep Delayed melatonin release Consider substance abuse Primary insomnia and other sleep disorders are unusual but need to be ruled out
31 Treating Adolescent Insomnia Screen patients for concurrent use of nonprescription remedies, alcohol, drug, pregnancy Rule out primary sleep disorders Emphasize sleep hygiene Avoid caffeine, excessive exercise, bright light Medications for short term use only No refills without reassessing target symptoms and evaluating patient compliance Choose medication with appropriate duration 32 Selected Drugs for Pediatric Insomnia Melatonin 1-10 mg Sleep promoter taken 30-45 min before bedtime Clonidine 0.025-0.3 mg Short action < 4 hrs Zolpidem 5-10 mg 6-8 hour effect; rare residual drowsiness Mirtazapine 15-45 mg Trazadone 25-100 mg Diphenhydramine 25-50 mg 33 Selected Drugs for Pediatric Insomnia Melatonin 1-10 mg Sleep promoter; taken 30-45 min before bedtime Clonidine 0.025-0.3 mg Short action < 4 hrs Zolpidem 5-10 mg 6-8 hour effect; rare residual drowsiness Mirtazapine 15-45 mg Trazadone 25-100 mg Diphenhydramine 25-50 mg Little evidence for chronic usage, side effects include paradoxical activation, increased seizures
34 Delayed Sleep Phase Syndrome Inability to sleep at socially appropriate time Night owl No objective sleep abnormality Can sleep in and awaken refreshed if allowed to extend time in bed Consider secondary gain Unusual schedule avoids both parental control of night activities and school attendance 35 Treating Delayed Sleep Phase Syndrome in Adolescents Melatonin 3-10 mg 30-45 min before lights out Chronotherapy Gradually advance bedtime by 10-15 min or delay bedtime by 2-4 hours per night until desired effect achieved Importance of strict adherence to schedule once entrained Light therapy AM light resets biological clock Medication as last resort 36 Sleep and Developmental Disorders
37 Sleep and Epilepsy 60% of children with epilepsy have seizures while asleep Secondarily generalized nocturnal seizures Benign rolandic epilepsy Facial twitching, speech arrest, drooling, secondary generalization Nocturnal frontal lobe epilepsy Bizarre clinical manifestations (thrashing, laughter, agitation, bicycling movements) 38 Sleep and Epilepsy Drowsiness and non-rem sleep facilitate epileptic discharges Seizures can disrupt sleep; post-ictal lethargy can disrupt sleep-wake schedule Drugs can lead to sleepiness or insomnia Disturbed sleep can lead to cognitive-behavioral deterioration Children with epilepsy not immune to inadequate sleep and/or primary sleep disorders *Bottom line: better sleep may improve seizure control 39 Epilepsy and Sleep Apnea Apnea associated with increased seizures Almost 1/3 of patients with intractable epilepsy have sleep apnea Treatment of apnea improves seizure control AEDs causing weight gain (valproate, carbamazepine, gabapentin) may induce or worsen apnea Sedating AEDs (phenobarbital, clonazepam) produce upper airway relaxation and reduce arousability
40 Sleep and Selected Genetic Syndromes Down syndrome (obstructive apnea) Obesity, mid-facial and mandibular hypoplasia, marcoglossia, adenotonsillar enlargement Smith-Magenis syndrome (severe insomnia) Sleep disorders in >75% Abnormal melatonin production 41 Sleep and Autism Severe sleep problems independent of cognitive level Most sleep disorders are behavioral Inappropriate sleep associations Stereotypies - headbanging, rocking Excessive anxiety, rituals Communication problems Must consider nocturnal seizures and epileptic autistic regression 42 Sleep and ADHD Frequent settling problems, restless sleep, night arousals, early arousals or difficulty awakening Primary sleep disorders rarely cause ADHD, but may exacerbate symptoms Obstructive sleep apnea PLMS Sleep phase disorders
43 Sleep and ADHD Co-morbid conditions may contribute to sleep problems Depression Anxiety disorders Migraine Medication issues Stimulants may decrease sleep need Rebound hyperactivity if stimulants wear off too early Parenting factors Child allowed to set own schedule to avoid tantrums 44 Sleep and Tourette Syndrome Sleep onset difficulties, restless sleep, early awakening PSG may show sleep fragmentation or persistence of tics in all sleep stages Increased incidence of parasomnias and migraine Sleep abnormalities increased with co-morbid ADHD and anxiety/ocd 45 Recent Sleep Research in Tourette Syndrome 80% of unselected university based clinic patients age 7-17 had > 1 sleep related problem sleep onset insomnia poor sleep efficiency frequent arousals parasomnias nightmares 20% had > 4 sleep related problems Sleep problems linked to reduced quality of life Anxiety linked to increased problems Storch et al, 2009
46 Back to the Basics: When to Suspect Underlying Sleep Disorder Delayed sleep onset Prolonged or frequent night awakenings Restless sleep Snoring, apnea Decreased total sleep time ADHD, irritability, aggression Excessive daytime sleepiness 47 Summary: Treating Sleep Disorders in Developmental Disabilities Always identify and treat underlying medical condition Epilepsy Cardiorespiratory problems including apnea, hypoventilation Pain muscle spasms, contractures Medication effects stimulants, sedatives, AEDs, 48 Summary: Treating Sleep Disorders in All Children Sleep hygiene Consistent bedtime and regular sleep routine Consistent morning awakening Maintain daytime wakefulness Allow appropriate naps Non-pharmacologic treatment Chronotherapy Light therapy Sleep-promoting drugs, only if necessary
49 Summary: Treating Sleep Disorders in All Children Pharmacotherapy Melatonin 1-10 mg 30-45 min before sleep Clonidine 0.05-0.3 mg Mirtazipine 15-45 mg Trazadone 25-100 mg Intermittent benzodiazepines acceptable Avoid diphenhydramine, if possible 50 Selected References: Meltzer LJ et al. Sleep and sleep disorders in children and adolescents. Psychiatric Clinics of North America. 29: 1059-1076, 2006. Mindell JA et al. Pharmacologic management of insomnia in children and adolescents: consensus statement. Pediatrics 117: e1223-1232, 2006. Kotagal S. Parasomnias in childhood. Sleep Medicine Reviews 13: 157-168. 2009. Koh S et al. Sleep apnea treatment improves seizure control in children with neurodevelopmental disorders. Pediatric Neurology 22: 36-39, 2000. Storch EA et al. Sleep-related problems in youth with Tourette s syndrome and chronic tic disorder. Child and Adolescent Mental Health 14: 97-103, 2009 51