Frankie Roman M.D. J.D. Unity Health Network Focus Conference May 16, 2014

1. Sudden Infant Death Syndrome Frankie Roman M.D. J.D.Unity Health NetworkFocus ConferenceMay 16, 2014

2. SIDS - Definition • Sudden death of an infant ( < 12 months) • Death unexplained after a thorough investigation - review of history - complete autopsy - death scene examination

3. SIDS • Accounts for 0.6 deaths per 1000 live births in Western countries • Single most common cause of death in the post neonatal period (35%-55%) • 2/3 of SIDS death occur in infants aged 2-4 months • 90% of deaths occur in children <8 months • Few deaths occur in children < 1 month and > 8 months

4. Triple Risk Model

5. Critical Development Period • Unique age of occurrence: peak between 2-4 months • Doubling of the brain weight • Rapid changes that occur for functional integration of brain stem regions that subserve cardiorespiratory control • Dramatic developmental changes in sleep state organization, arousal, cardiorespiratory control and metabolism

6. Vulnerable Infant • Abnormal homeostatic control during sleep • Altered ventilator drive • Altered autonomic control • Neurotransmitter and functional nerve cell abnormalities • Arcuate nucleus deficiencies • Prematurity

7. Ex0genous Stressors • Infection • Child rearing practices – lower rates of pacifier use • Prone position of the baby • Over bundling and changes in ambient temperature • Tobacco smoke exposure

8. Prone Position • Higher risk for SIDS • Mechanisms - increased sleep duration - increased quiet sleep - fewer short arousals - rebreathing exhaled CO2 - upper airway obstruction - overheating due to decreased body heat dissipation

9. Apparent Life –Threatening Event ( ALTE) • An episode that is frightening to the observer • Characterized by some combination of apnea, color change, change in muscle tone, choking or gagging

10. Etiology Of ALTE

11. ALTE: Identifiable Causes

12. Recommended Evaluation for ALTE • Admission and observation with CR monitoring • History, physical and neurological examination • CBC , electrolytes, calcium, CXR, ECG, EEG

13. Evaluation of ALTE in selected cases • Sepsis work up • Barium swallow • Esophageal ph study • US/CT of Brain • Echocardiogram • Blood ammonia and urine amino acids • Polysomnogram

14. Indications for Home Cardiopulmonary Monitoring • 3 decades of monitor use did not prevent SIDS • Significant ALTE for which no cause was found • Twin of SIDS • Multichannel documentation of clinically significant apnea

15. ALTE

16. Congenital Central Hypoventilation Syndrome (CCHS) • Failure of autonomic control of breathing • Rare disorder – 1 per 200,000 live births • Disordered ventilation control may range in severity - hypoventilation during sleep with adequate ventilation during wakefulness - severe cases: hypoventilation during both sleep and wakefulness

17. CCHS • Minute ventilation is reduced during sleep due to reduction in tidal volume with relatively well preserved breathing frequency. • Hypoventilation is worse during NREM sleep ( chemical control of breathing). • Decreased or absent ventilator chemo sensitivity in response to hypoxia and hypercapnia during wakefulness and sleep. • Thus children cannot generate signs of respiratory distress. • Hypercapnic arousal (exogenous) responses appear intact. • Abnormality is located in the area of brain stem responsible for integration of chemoreceptor signals.

18. Clinical Features - Respiratory • Age – typically new born period, also child and adulthood. • Lack of perception of asphyxia during wakefulness with or without exertion • Absence of primary lung, cardiac or neuromuscular disease or brain stem lesion.

19. Clinical Features – Non respiratory • Autonomic nervous system dysfunction - Anatomic Hirschsprung’s disease ( 20% of CCHS) Tumors of neural crest origin ( neuroblastoma) - Physiological symptoms Decreased pupillary response, esophageal dysmotility, breath holding spells, temperature instability, abnormal heart rate variability and cardiac asystoles

20. Disease Presentation and Clinical Course • Majority symptomatic during the newborn period. • Fail to initiate respiratory effort requiring assisted ventilation from birth. • Late onset beyond neonatal period – can present with episodes of severe apnea, apparent life-threatening event or problems in recovery from sedation and anesthesia.

21. Assisted Ventilation • Tracheostomy - Positive pressure ventilation via tracheostomy • Noninvasive - nasal or face mask interface - bilevel positive pressure support in a spontaneous timed mode with back up rate • Negative pressure ventilators • Diaphragmatic pacing

22. Positive Pressure Ventilation via Tracheostomy • Most common method used for children needing 24 hour ventilator y support. • Ventilation can be accomplished via portable home ventilators in volume control/pressure control mode. • Nocturnal hyperventilation with end tidal CO2 values in the 30-35 mg range can lead to improvement in day time ventilation.

23. Noninvasive Ventilation • Increasingly used, well tolerated even in younger children. • Effective mode of ventilation for children who need only night time support. • Bilevel ventilation – difference in IPAP and EPAP generates adequate tidal volume • Back up rate is dialed in to assure minute ventilation

24. Summary of CCHS • Hallmark of CCHS is absent ventilatory response to CO2 and O2. • Exclusion diagnosis – need to rule out primary lung disease, ventilatory muscle weakness, gross anatomic brain or brain stem lesions and inborn errors of metabolism. • Can present in later infancy, child and adulthood. • Majority of the affected patients require lifelong ventilatory support. • 95% of cases identified by PHOX2 • If negative, additional screening PHOX2B sequencing test identifies subset of non- polyalanine repeat mutations (NPARM)