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Jess P. Shatkin, MD, MPH Vice Chair for Education NYU Child Study

“ To Sleep… Perchance To Dream ” The Diagnosis and Treatment of Children and Adolescents with Sleep Disorders. Jess P. Shatkin, MD, MPH Vice Chair for Education NYU Child Study New York University School of Medicine. Outline of Presentation. Review of Normal Sleep Physiology

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Jess P. Shatkin, MD, MPH Vice Chair for Education NYU Child Study

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  1. “To Sleep…Perchance To Dream”TheDiagnosis and Treatment of Childrenand Adolescents with Sleep Disorders Jess P. Shatkin, MD, MPH Vice Chair for Education NYU Child Study New York University School of Medicine

  2. Outline of Presentation • Review of Normal Sleep Physiology • Neurocognitive Effects of Sleep Disruption • Common Sleep Disorders • Insomnia • Sleep Disordered Breathing • Non-REM Parasomnias • Enuresis • Sleep in Children with Common Psychiatric Conditions

  3. Polysomnogram (PSG) • Electroencephalogram (EEG) • Electromyogram (EMG) • Electrooculogram (EOG) • Vital Signs • Other Physiologic Parameters

  4. Other Methods to Study Sleep • Ambulatory Techniques • Edentrace System (monitors pulse, body position, oro-nasal flow, chest impedance, breathing noises, and pulse oximetry) • Actigraphy (commonly used, developed in the early 1970s and has come into increasing use in both research studies and clinical practice; allows for the study of sleep-wake patterns and circadian rhythms via the assessment of body movements. The device is typically worn on the wrist and can easily be adapted for home use. Reliable and valid for the study of sleep in normal, healthy populations but less reliable for detecting disturbed sleep) • Survey Instruments • Many exist for detecting problematic sleep in children and adolescents, including self-report questionnaires (such as the Sleep Disturbance Scale for Children, the Child Sleep Questionnaire, and the Child and Family Sleep History Questionnaire), sleep diaries, and parent report forms.

  5. EEG Sleep Patterns

  6. Important Concepts and Terms • Sleep Latency • REM Latency • REM Density • REM Rebound • Sleep Onset REM Period

  7. Non-REM Physiological Changes • Reduced physiological activity • Autonomic slowing • Maintain thermoregulation • Episodic, involuntary movements • Few rapid-eye movements • Few penile erections (little vaginal lubrication) • Reduced blood flow

  8. REM Physiological Changes • Increased physiological activity • Autonomic activation • Altered thermoregulation • Partial or full penile erections (significant vaginal lubrication) • Skeletal muscle paralysis • Rapid-eye movements

  9. The Sleep Cycle • Cyclic nature of sleep is reliable • REM periods every 90 – 120 minutes • First REM period is shortest • Most deep sleep (Stage 3 & 4) occurs early • Most REM occurs late

  10. Normal Sleep Cycle in Children Awake REM Stage 1 Stage 2 Stage 3 Stage 4 1 2 3 4 5 6 7 Hours of Sleep

  11. Normal Sleep Cycle in Young Adults Awake REM Stage 1 Stage 2 Stage 3 Stage 4 1 2 3 4 5 6 7 Hours of Sleep

  12. Normal Sleep Cycle in the Elderly Awake REM Stage 1 Stage 2 Stage 3 Stage 4 1 2 3 4 5 6 7 Hours of Sleep

  13. Sleep Regulation • No clear, single center • Serotonin & Catecholamines (EPI, NOREPI, DA) • “REM off” cells • GABA • Acetylcholine • “REM on” cells • Suprachiasmatic nucleus • 25 hour cycle? • Orexin/hypocretin • Pineal gland (melatonin)

  14. Neuroendocrine Activity in Sleep • Growth Hormone • Prolactin • Luteinizing Hormone • Cortisol • Thyroid Stimulating Hormone (TSH)

  15. Function of Sleep • Restorative/homeostatic • Thermoregulation/energy conservation • Consolidation of learning and memory • Programming of species-specific behaviors • “to sleep, perchance to dream, ay there’s the rub” • William Shakespeare (Hamlet)

  16. Dreams Sleep hath its own world, A boundary between the things misnamed Death and existence: Sleep hath its own world, And a wide realm of wild reality, And dreams in their development have breath, And tears and tortures, and the touch of joy. —Lord Byron

  17. Dreams • REM dreams • Non-REM dreams • Motor paralysis • Rapid-eye movements • Dream content • Predominantly sad/angry/apprehensive • Primarily visual

  18. Neurocognitive Effects of Sleep Disruption: Attention and Memory • Limited data in children; most info based upon the effects of sleep disordered breathing (SDB) on daytime performance • Sleep restriction in experimental settings results in inattention and changes in cortical EEG responses (even after only 1 hour restriction) • Data are inconsistent on the effects of sleep disruption on memory performance • Children suffering from Obstructive Sleep Apnea (OSA), Periodic Limb Movement Disorder (PLMD), and Restless Leg Syndrome (RLS) with resulting sleep fragmentation have been shown to suffer academic deficits, learning problems, and symptoms that mirror ADHD • In the case of OSA, symptoms are generally reversible after treatment

  19. Neurocognitive Effects of Sleep Disruption: Psychometric Testing • Sleep restriction and total sleep deprivation have been shown to reduce computational speed, impair verbal fluency, & decrease creativity and abstract problem solving ability • Severe sleep fragmentation (e.g., as seen in OSA) may result in reduced intelligence scale scores (IQ)

  20. Neurocognitive Effects of Sleep Disruption: Academic Achievement • Children with OSA suffer lower academic achievement (even when age, race, gender, SES, and school attended are controlled for) • Treatment of OSA results in significant improvement in school performance • Children who snore loudly and consistently in early years are at greater risk for academic delays in later years, suggesting residual effects on learning even after resolution of symptoms • Animal models show increased neuron cell loss in the hippocampus and PFC in rats exposed to intermittent hypoxia; along with decreases in special task acquisition and retention and increased locomotor activity compared to controls

  21. Sleep Disorders in Children • ~25% of children will suffer some type of sleep problem at some point during childhood • Complaints range from bedtime resistance and anxiety to primary sleep disorders, such as OSA and narcolepsy • Research is remarkably consistent, with parents reporting 50% of preschool children, 30% of school aged children, and 40% of adolescents as having sleep difficulties • Self-report among adolescents reveals 14 – 33% complaining of frequent or extended nighttime awakenings, EDS, unrefreshing sleep, early insomnia, and a subjective need for more sleep

  22. Sudden Infant Death Syndrome • A worldwide decline in the past decade • Incidence at roughly 0.77 per 1000 live births in Great Britain; incidence in the United States has dropped by more than 50% from 1.53 per 1000 live births in 1980 to 0.56 per 1000 live births in 2001 • Still, SIDS accounted for 8% of all infant deaths in the United States in 2002 and ranks as the third leading cause of infant death in the United States • The most widely accepted definitions of SIDS require that all other known possible causes of death be ruled-out by death scene investigation, review of the clinical history, and autopsy prior to accepting SIDS as the diagnosis (e.g., intentional or nonintentional injury, suffocation, etc). • Efforts aimed at reducing modifiable risk factors for infants, such as sleeping in a prone position, over-bundling, and secondary smoke exposure, have reduced the incidence of SIDS by more than 60% in most parts of the world. • Other strategies, such as sleeping solitary in a supine position, not allowing infants to sleep on their sides, and using a pacifier, may ultimately reduce the incidence still further. • In the United States, the SIDS rate for African and Native American infants remains more than twice that of Caucasian infants, reflecting a long-standing racial disparity.

  23. DSM IV Sleep Disorders:Dyssomnias • Primary Insomnia • Primary Hypersomnia • Narcolepsy • Breathing Related Sleep Disorder • Circadian Rhythm Sleep Disorder • Dyssomnia NOS

  24. Primary Insomnia in the General Population • Early and middle insomnia • PSG studies are negative • Sub-clinical symptoms of psychiatric illness often present • More common w/increasing age and in women • Prevalence: 1 – 10% in general population; up to 25% in elderly • Generally sudden onset w/continuation due to negative conditioning and development of maladaptive sleep patterns

  25. Pediatric Insomnia • No clear definition has existed until this year: “Repeated difficulty with sleep initiation, duration, consolidation, or quality that occurs despite age-appropriate time and opportunity for sleep and results in daytime functional impairment for the child and/or family.” • International Classification of Sleep Disorders-2

  26. Pediatric Insomnia (2) • Prevalence estimated at 1 – 6 % in general pediatric population but considerably higher amongst those children with neurodevelop-mental delay and chronic med/psych conditions • A recent study of 46 children (5-16 y/o) found that 50% of the those presenting to a pediatric sleep center for insomnia had a preexisting psych diagnosis and the remaining 50% had elevated psych impairment scores on psychometric measures & diagnostic interview (Ivanenko et al, 2004)

  27. Behavioral Insomnia • A recently introduced diagnostic category to emphasize the sleep difficulties resulting from inadequate limit setting or sleep associations: • Rocking • Watching TV • Falling asleep every night in the parent’s bed • The child is unable to fall asleep in the absence of these conditions at both bedtime and following nocturnal awakenings

  28. Case #1: Insomnia • James is a 15 year-old male with a childhood history of moderate separation anxiety for which he never received treatment. He has a history of mild/moderate sleep disruption (primarily early and occasional middle insomnia), but over the past 6 weeks he has suffered increasing insomnia concurrent with an increase in school stressors. He presents to you with complaints of a two hour sleep onset latency 4x/week and nightly nocturnal awakenings with difficulty falling back to sleep. • How do you proceed?

  29. Treatment of Insomnia: Sleep Hygiene • Identify the cause or other Axis I disorder (if possible) and treat • Set a sleep/wake schedule • Exercise daily but not at night • Avoid caffeine, cigarettes, alcohol, and drugs • Invent a relaxing bedtime ritual (e.g., bathing, reading, watching TV, etc.) • Use the bed for sleeping or sex, nothing else • Wake up to the sun, exposing yourself to morning sunshine • Adjust the room temperature as desired

  30. Treatment of Insomnia (2): Medication • No FDA approved treatments • Sedatives are short-term solutions • A shorter half-life is typically preferred • Sedating antihistamines (diphenhydramine, hydroxyzine, cyproheptadine) • Alpha-2 agonists (clonidine, guanfacine) • Sedating antidepressants (Trazodone, Serzone, Remeron, TCAs,) • Benzodiazepines and similar agents (Sonata, Ambien, Lunesta, Rozarem) preferred over barbiturates • Tolerance to somnolent effects of Benzos develops in about 4 weeks (not anxiolytic effects) • HM/DS: Melatonin, Kava, Valerian, L-tryptophan, chamomile, passion flower, lavender, etc

  31. Sleep Disordered Breathing (SDB) • Primary Snoring • regular snoring without changes in sleep architecture, alveolar ventilation, or oxygenation • Upper Airway Resistance Syndrome • Similar to OSA but UARS does not result in blood oxygen desaturations • Obstructive Sleep Apnea • Results in blood oxygen desaturations

  32. SDB: Epidemiology • Primary Snoring *Prevalence = 7 – 12% • Upper Airway Resistance Syndrome *Estimates difficult to ascertain • Obstructive Sleep Apnea *Prevalence = 1 – 2%

  33. SDB Clinical Presentation • Parents complain of: • Snoring • Frequent awakenings • Excessive Daytime Sedation • Poor academic performance • Irritability • Poor executive function • Inattention/general cognitive impairment

  34. SDB Evaluation and Treatment • Labs show: • A reduction in airflow and Hgb saturation • Increased total Hgb • Cardiac arrhythmias (sinus arrhythmias, PVCs, AV block, sinus arrest) • Stage 1 >> 3,4 & REM • Physical Examination shows: • Adenotonsillar enlargement • Pectus excavatum & rib flaring • More commonly in adults: obesity, >17” neck size, HTN, cor pulmonale

  35. Treatment of Sleep Apnea • Weight loss • Sleep on sides (and stomach) • CPAP (Continuous Positive Airway Pressure) prevents obstruction by soft-tissue and keeps airway open • Surgical intervention (e.g., enlarged tonsils, deviated septum) • Avoid sedatives (which can prevent reawakening to breathe)

  36. DSM IV Sleep Disorders:Non-REM Parasomnias • Somnambulism • Sleep/Night Terrors • Somniloquy • Enuresis • Sleep Related Involuntary Movement Disorders • PLMD • Body Rocking • Bruxism

  37. Enuresis: Epidemiology & Diagnosis • Occurs in approximately 30% of 4 y/o, 10% of 6 y/o, 5% of 10 y/o, 3% of 12 y/o, and 1% of those 15 y/o and over • Although not satisfying DSM-IV criteria for diagnosis, 10 – 20% of 5 y/o continue to have a least one episode of nocturnal enuresis/month • DSM-IV requires: • Frequency at least 2x/week for at least 3 months • age at least 5 years

  38. Enuresis: Etiology • Primary enuresis (never consistently dry) • Multifactorial etiology w/difficulties in: bladder musculature stability, CNS arousability, pontine reflex function, internal sphincter tone, functional bladder capacity, nocturnal urine production, & maturational delay in ADH secretion • Secondary enuresis (previously dry for 6 mo) • UTI, diabetes mellitus, psychological factors

  39. Associated Features • Nocturnal enuresis is associated with poor self-image, diminished achievement in school, and an increase in the time spent by families compensating, both financially and personally, for the symptoms. • Risk factors (twice as common in boys>girls, family history, lower SES, black race)

  40. Case #2: Enuresis • Ryan is a 10 y/o male with a history of mild MR, ADHD (CT), and severe ODD with a rule-out of Bipolar D/O NOS. He also suffers nightly enuresis. Current medications include Concerta 54 mg qAM and Risperdal 0.25 mg BID. His parents have tried numerous behavioral interventions with no success. Ryan has previously been treated with desmopressin acetate to 4 mg hs and imipramine to 50 mg hs. • What questions do you have? • How would you proceed?

  41. Enuresis: Treatment (1) • Full history (e.g., nature of “behavioral” treatments tried, how medications were used) • Psycho-education for family and patient • Discontinue all caffeine and EtOH • Restrict late night fluid intake • Afternoon nap (to decrease Stage III/IV) • Brief awakening for toileting at midnight

  42. Enuresis: Treatment (2) • Behavioral Treatments: • Bedwetting alarm (highest cure rate, lowest relapse rate) • Bladder training to increase capacity • Reward systems • Cognitive & motivational therapy • Pelvic floor muscle training • Biofeedback

  43. Enuresis: Treatment (3) • Medications: • Desmopressin acetate (DDAVP) • Intranasal (10 – 60 mcg) vs. oral (0.1 – 0.6 mg) • Imipramine or amitriptylene • 25 – 50 mg • Anticholinergic (antispasmodic) agents • Oxybutinin (Ditropan) 2.5 – 5 mg or tolterodine (Detrol) 0.5 – 1 mg • Combination treatment • DDAVP + oxybutinin or DDAVP + TCA • Atomoxetine (Strattera)

  44. Non-REM Sleep Disorders and Unconscious Actions • Doctor: “You see, her eyes are open.” • Lady-in-Waiting: “Ay, but their sense are shut.” • William Shakespeare (The Tragedy of MacBeth)

  45. Non-REM Sleep Parasomnias:Shared Features • 1 – 30 minutes • Retrograde amnesia • Family/personal history • High potential for injury to self and others • Occur during slow-wave sleep • More common in childhood • Attempts to awaken are fruitless • Psychopathology rare in children

  46. Non-REM Sleep Parasomnias:Precipitating Factors • Dyssomnia • Sleep deprivation • Medications • Magnesium deficiency • Hormonal factors

  47. Sleep Terrors • Infrequent occurrence • Prevalence 3–6.5% in children, 1–2.6% in adults • Autonomic activation • 30 seconds – 3 minutes • Complete amnesia • Gender preference • Males typically in childhood • Females possibly more common in adulthood

  48. Sleepwalking • Common occurrence • Prevalence 6-17% in children; lifetime incidence 40% • Prevalence 2.5% in adults • Generally docile • Often coupled with enuresis • No consistent gender differences • Complete amnesia • May engage in complex behaviors

  49. Confusional Arousal • Epidemiology unclear • 4% incidence in Stockholm study • No gender differences noted • Hallmarks include irrational acts, poor judgment, incoherence, and disorientation • Autonomic arousal • Complete amnesia • Premeditated acts believed impossible

  50. Case #3: Non-REM Parasomnia vs. Suicide Attempt • Tracy is a well adjusted 12 y/o girl from an intact and loving family with no psychiatric history. One summer’s evening, an hour after going to bed, she was awoken with a severe sore throat. She stumbled to the mirror to find her throat cut wide open to her trachea with two 5” horizontal lacerations extending the breadth of her neck. A bloodied box cutter was found at her bedside; she had no memory of the event. • How would you make a diagnosis? • How would you treat this case?

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