1. By Dr. Lucy Suliman Lecture of chest medicine Sleep disordered breathing in neuromuscular diseases

2. Types of neuromuscular disease Anterior horn cell ALS Peripheral nerves poliomyelitis Neuromuscular junction Myathenia gravis Muscle Myotonic dystrophy, Duchenne myopathy, limb girdle muscular dystrophy

3. Types of Sleep disordered breathing in NMD Sleep hypoventilation syndrome Central sleep apnea Obstructive sleep apnea Chyne stoke breathing Nocturnal desaturation

4. Sleep hypoventilation syndrome 1 There is an increase in the arterial PaCO2 (or surrogate) to a value > 55 mm Hg for ≥ 10 m inutes. 2. There is ≥ 10 mm Hg increase in PaCO2 (or surrogate) during sleep (in comparison to an awake supine value) to a value exceeding 50 mm Hg for ≥ 10 minutes

5. The commonest form of sleep-disordered breathing in patients with respiratory muscle weakness is hypoventilation due to reduced tidal volume, particularly during REM sleep Similar REM-related hypoventilation has been described in several other situations (e.g. chronic obstructive pulmonary disease(COPD), cystic fibrosis and obesity hypoventilation syndrome.

6. Measurment of sleep hypoventilation end-tidal PCO2 (PETCO2) transcutaneous PCO2 (TcPCO2) for diagnostic study or (TcPCO2) for PAP titration study. end-tidal PCO2 (PETCO2) transcutaneous PCO2 (TcPCO2) for diagnostic study or (TcPCO2) for PAP titration study.

7. Obstructive sleep apnea 1. There is a drop in the peak signal excursion by ≥ 90% of pre-event baseline using an oronasal thermal sensor (diagnostic study), positive airway pressure device flow (titration study), or an alternative apnea sensor. 2. The duration of the ≥ 90% drop in sensor signal is ≥ 10 seconds.. 3. The classification of apnea as obstructive, mixed, or central in the 2014 scoring manual is based on respiratory effort.

8. Obstructive events are more likely in subjects with : 1 high body mass index (BMI) 2 snore 3 have anatomical abnormalities such as macroglossia (e.g. in DMD) 4 Increased UAR during REM sleep

9. classification of events as "central“ or"obstructive“ using noninvasive monitoring is particularly difficult in neuromuscular disease Obstructive apnoea may be misclassified as central when respiratory muscles are too weak to move the chest wall against a closed Pharynx.

10. Central sleep apnea The most frequently reported discrete sleep- breathing events in patients with respiratory muscle weakness are central apneas and hypopnoeas. Which are more frequent and prolonged in REM sleep particularly phasic REM due to suppression of the intercostal and accessory respiratory muscles. The most frequently reported discrete sleep- breathing events in patients with respiratory muscle weakness are central apneas and hypopnoeas. Which are more frequent and prolonged in REM sleep particularly phasic REM due to suppression of the intercostal and accessory respiratory muscles.

11. Severe diaphragmatic weakness causes parmovement of the chest and abdomen adoxical even without narrowing of the upper airway misclassification of central hypopnoeas as obstructive. An increasing phase difference between chest and abdominal movements

12. strong supportive evidence for an obstructive aetiology. 1 stable or increasing submental EMG (particularly at the end of the event) 2 phasic diaphragmatic EMG activity 3 snoring

13. Obstructive and central hypopneas

14. The recommended hypopnea definition 1A requires a 30% or greater drop in pre event baseline flow for 10 seconds or longer associated with ≥ 3% oxygen desaturation or an arousal. 1B requires a 30% or greater drop in preevent baseline flow for 10 seconds or longer associated with ≥ 4% oxygen desaturation

15. (A) central hypopnea is characterized by lack of flattening in the airflow (nasal pressure) and a reduction in respiratory effort (esophageal pressure excursions). The reduction in flow is chronologically parallel to the reduction in effort. (B) An obstructive hypopnea is characterized by airflow limitation (flattening of the nasal pressure waveform) and increasing respiratory effort without an increase in airflow (nasal pressure).

16. Obstructive hypopneas are usually associated with flattening of the inspiratory portion of the nasal pressure (or PAP device flow) Snoring thoracoabdominal paradox. Obstructive hypopneas are usually associated with flattening of the inspiratory portion of the nasal pressure (or PAP device flow) Snoring thoracoabdominal paradox.

17. Central hypopneas typically characterized by absence of :- flattening of the inspiratory portion of the nasal pressure or PAP flow wave form thoracoabdominal paradox in the thoracic and abdominal RIP band excursions. snoring. Central hypopneas typically characterized by absence of :- flattening of the inspiratory portion of the nasal pressure or PAP flow wave form thoracoabdominal paradox in the thoracic and abdominal RIP band excursions. snoring.

18. obstructive hypopneacentral hypopnea

19. esophageal pressure and diaphragmatic electromyogram can be used, but are invasive and require specialized equipment not available in most sleep laboratories. These techniques are not suitable for routine monitoring, but are usually reserved for research purposes. esophageal pressure and diaphragmatic electromyogram can be used, but are invasive and require specialized equipment not available in most sleep laboratories. These techniques are not suitable for routine monitoring, but are usually reserved for research purposes.

20. Chyne stoke breathing

21. 1. There are episodes of at least 3 consecutive central apneas and/or central hypopneas separated by a crescendo and decrescendo change in breathing amplitude with a cycle length of at least 40 seconds (typically 45 to 90 seconds). 2. There are 5 or more central apneas and/or central hypopneas per hour associated with the crescendo/decrescendo breathing pattern recorded over a minimum of 2 hours of monitoring 1. There are episodes of at least 3 consecutive central apneas and/or central hypopneas separated by a crescendo and decrescendo change in breathing amplitude with a cycle length of at least 40 seconds (typically 45 to 90 seconds). 2. There are 5 or more central apneas and/or central hypopneas per hour associated with the crescendo/decrescendo breathing pattern recorded over a minimum of 2 hours of monitoring

22. Nocturnal desaturation in neuromuscular disease,

23. Causes of NOD in NMDs 1 overall hypoventilation 2 periodic apnoeas and hypopnoeas 3 ventilation/perfusion mismatching due to increased atelectasis in the supine posture

24. orthopnea Excessive day time sleepness NOD

25. Features specific to individual disorders

26. Isolated diaphragmatic paralysis Subjects with isolated diaphragmatic paralysis are prone to nocturnal desaturation during REM sleep even with only unilateral involvement REM sleep and slow-wave sleep (SWS) are likely to be reduced. Daytime respiratory failure is unusual with isolated bilateral diaphragmatic paralysis unless there is coexisting intrinsic lung disease (e.g. COPD) or obesity. Subjects with isolated diaphragmatic paralysis are prone to nocturnal desaturation during REM sleep even with only unilateral involvement REM sleep and slow-wave sleep (SWS) are likely to be reduced. Daytime respiratory failure is unusual with isolated bilateral diaphragmatic paralysis unless there is coexisting intrinsic lung disease (e.g. COPD) or obesity.

27. Amyotrophic lateral sclerosis the frequency of sleep disordered breathing is very variable (16.7–76.5%) Diaphragmatic paresis or paralysis is associated with sleep disruption and reduction or complete suppression of REM. the frequency of sleep disordered breathing is very variable (16.7–76.5%) Diaphragmatic paresis or paralysis is associated with sleep disruption and reduction or complete suppression of REM.

28. No significant relations between bulbar involvement and the severity of sleep- disordered breathing or the type of event (obstructive or central). Nocturnal desaturation and sleep disruption in ALS appear to be due to mainly diaphragmatic weakness and hypoventilation, rather than due to bulbar weakness No significant relations between bulbar involvement and the severity of sleep- disordered breathing or the type of event (obstructive or central). Nocturnal desaturation and sleep disruption in ALS appear to be due to mainly diaphragmatic weakness and hypoventilation, rather than due to bulbar weakness

29. Myotonic dystrophy Daytime somnolence, hypercapnia, sleep- disordered breathing and nocturnal desaturation are all common in MD AHI and degree of nocturnal desaturation are greater than in nonmyotonic neuromuscular disease with a similar degree of respiratory muscle weakness. MD is also associated with an irregular breathing pattern during wakefulness and light sleep. Daytime somnolence, hypercapnia, sleep- disordered breathing and nocturnal desaturation are all common in MD AHI and degree of nocturnal desaturation are greater than in nonmyotonic neuromuscular disease with a similar degree of respiratory muscle weakness. MD is also associated with an irregular breathing pattern during wakefulness and light sleep.

30. Myasthenia gravis Sleep related symptoms in myasthesia gravis (MG) might reflect central nervous system involvement or occur as a side-effect of anticholinesterase therapy Sleep-disordered breathing is common in MG associated with peripheral respiratory muscle weakness, particularly diaphragmatic weakness. Sleep related symptoms in myasthesia gravis (MG) might reflect central nervous system involvement or occur as a side-effect of anticholinesterase therapy Sleep-disordered breathing is common in MG associated with peripheral respiratory muscle weakness, particularly diaphragmatic weakness.

31. Central sleep apnea and nocturnal desaturation are most pronounced during REM. Sleep-disordered breathing and nocturnal desaturation may improve following treatment with thymectomy or prednisolone. Central sleep apnea and nocturnal desaturation are most pronounced during REM. Sleep-disordered breathing and nocturnal desaturation may improve following treatment with thymectomy or prednisolone.

32. Duchenne muscular dystrophy DMD using automated analysis reported apnoeas, which initially were mainly obstructive, but with disease progression the proportion of central apnoeas increased. Authors suggested that the apparent increase in central events in serial studies may be due to misclassification ("pseudo-central“ events) DMD using automated analysis reported apnoeas, which initially were mainly obstructive, but with disease progression the proportion of central apnoeas increased. Authors suggested that the apparent increase in central events in serial studies may be due to misclassification ("pseudo-central“ events)

33. In comparison to subjects with ALS and a similar impairment of daytime respiratory function, sleep architecture appears to be better preserved in DMD.

34. Home messages

35. Respiratory muscle weakness in neuromuscular disease causes significant morbidity and mortality. In subjects with respiratory muscle weakness sleep is fragmented, with shorter total sleep time, frequent arousals, an increase in stage 1 sleep and a reduction in, or complete suppression of, REM sleep. Sleep hypoventilation is The commonest form of sleep-disordered breathing in patients with respiratory muscle weakness

36. classification of events as "central" or"obstructive“ using noninvasive monitoring is particularly difficult in neuromuscular disease. The most profound desaturation and SDBD (obstructive or central) occurs during REM particularly phasic REM. Classification of events (central or obstructive) is benificial to detect type of NIPPV for each patient