2. Objectives
• Identify clinical signs of impending
respiratory failure
• List 3 lung function tests used to
monitor patients with neuromuscular
disease for respiratory failure
• Define Non-Invasive Ventilation
2 of 56
10. Duchenne Muscular Dystrophy
• Genetics
– X-linked recessive (males)
– Chromosome X, DMD gene
• Cause
– Dystrophin protein needed for muscle cell interaction
• Onset
– 2-6 years of age degenerative disease
• Symptoms
– Proximal muscle weakness, affects respiratory and
cardiac muscle
10 of 56
11. Duchenne Muscular Dystrophy
http://upload.wikimedia.org/wikipedia/commons/4/49/Duchenne-muscular-dystrophy.jpg
Accessed on September 20, 2010
11 of 56
14. Nemaline Myopathy
• Genetics
– Autosomal recessive and dominant forms
– First discovered in 1956 by Dr. Reyes
– 1/50,000 births
– 6 different mutations identified
• Onset
– Infancy and early childhood
• Clinical presentation
– Face, neck and proximal muscle weakness
– Absent deep tendon reflexes (DTR), normal creatinine
kinase
14 of 56
16. Myotubular Myopathy
• A form of centronuclear myopathy
• Genetics
– X-linked recessive
– Autosomal recessive and dominant
• Onset
– Birth for X-linked recessive
– Infancy and childhood for autosomal recessive
– Adult for autosomal dominant
• X-linked is most common form and most severe
• Clinical
– Hypotonia, respiratory pump failure, scaphocephaly
16 of 56
17. Myotubular Myopathy
http://www.mtmrg.org/MTM%20Article%20by%20CR.PDF
Accessed 9/20/10
17 of 56
18. Myotubular Myopathy
http://www.mtmrg.org/MTM%20Article%20by%20CR.PDF
Accessed 9/20/10
18 of 56
25. Congenital Fiber-Type Disproportion
• Genetics
– 3 different mutations, usually present first year of
life
• Clinical
– Hypotonia, weakness, delayed motor development
first year of life
– 90% static or slow improvement over time
– Contractures at birth
– Scoliosis
– Dislocated hips
25 of 56
26. Congenital Fiber-Type Disproportion
http://brain.oxfordjournals.org/content/vol128/issue7/images/large/awh511f5.jpeg
Accessed 9/20/10
26 of 56
29. SMA
• Genetics
– Autosomal recessive
– 1/6000 births
– 1/40 carriers
– SMA1 and SMA2 identified to chromosome 5q
in 1995
– Variable based on specific genetic defect
29 of 56
30. SMA Types
• Type 1
• Type 2
• Type 3
• Type 4
• Non-5q-SMA’s
30 of 56
31. Incidence SMA at Birth
12%
Type 1
27% 60% Type 2
Type 3
31 of 56
32. Prevalence SMA in Population
14%
35%
Type 1
Type 2
Type 3
51%
32 of 56
33. SMA Type 1
• Werdnig-Hoffman Disease
• Severe
• Age of onset 0-6 months
• Never sits, flaccid paralysis, absent deep
tendon reflexes, tongue fasiculations
• Life expectancy < 2 years
33 of 56
35. SMA Type 2
• Intermediate severity
• Age of onset 7-18 months
• Sits but never stands
• Life expectancy > 2 years
35 of 56
36. SMA Types 3 and 4
• SMA 3
– Kugelberg-Welander Disease
– Mild severity
– Age of onset > 18 months
– Function stands and walks
– Life expectancy - adult
• SMA 4 (adult form – rare)
– Very mild severity
– Presents 2nd and 3rd decade
– Ambulatory
36 of 56
39. Anterior Horn Cell Disease
http://www.anatomyatlases.org/MicroscopicAnatomy/Images/Plate89.jpg and
www.anatomyatlases.org/MicroscopicAnatomy/Section06/Plate0689.shtml
Accessed both websites 9/20/10
39 of 56
40. Classification:
Diseases of the Neuromuscular Junction
• Congenital myasthenic syndromes
• Myasthenia gravis
– Acetylcholine junction
40 of 56
41. Pathophysiology of Myasthenia Gravis
http://jama.ama-assn.org/content/vol293/issue15/images/medium/jpg0420f1.jpg
Accessed 9/20/10
41 of 56
43. Complications of Neuromuscular Disease
• Scoliosis
• Bulbar Dysfunction
– Swallowing dysfunction, speech
• Osteoporosis
• Respiratory Failure
• Cardiomyopathy/Congestive Heart
Failure
• Early Death
43 of 56
44. Monitoring for Respiratory Failure
• Serial monitoring of lung function when able to
be performed (> 5 years of age)
– FVC < 1 liter
• Close monitoring, consider NIV
– FVC < 40% of predicted (nocturnal hypoventilation)
• Refer for polysomnography
– MIP < 40 cm H2O MEP < 45 cm H2O
• Polysomnography, consider day/night CO2
– Peak Cough Flows < 270 L/min in older children
• Monitor closely for respiratory failure
– Wheelchair bound
• Consider overnight sleep monitoring
– Upper airway obstruction
• Adenotonsillectomy (CPAP if no hypertrophy)
– Chronic hypercarbia or acute respiratory failure
• NIV
44 of 56
51. NIV and Airway Clearance
• First used in the 1960’s
• First suggested for use in 1980’s for NMD
• May reduce incidence of respiratory
infections
• Techniques to improve pulmonary toilet –
breath stacking, cough assist devices
• Possible benefit of high-frequency chest
wall oscillation and intrapulmonary
percussive ventilation
51 of 56
52. Non-Invasive Ventilation
• According to international consensus,
NIV is defined as any form of
ventilatory support applied without
endotracheal intubation and includes
bipap, cpap and other modes
52 of 56
55. Conclusions
• Marked improvement in management of
respiratory complications of neuromuscular
disease in past 15 years
• Serial monitoring for progressive respiratory
pump failure necessary to minimize pulmonary
complications
• Early implementation of therapies to treat
hypoventilation and promote airway clearance
may augment quality and quantity of life
55 of 56