SMA

1. SMA Nanci Yuan, MD LPCH/Stanford Medical Center May 17, 2006

2. Spinal Muscular Atrophy (SMA) • Spinal muscular atrophy (SMA) is a genetic, motor neuron disease caused by progressive degeneration of motor neurons in the entire spinal cord and in select brainstem motor nuclei (nuclei of cranial nerves V, VII, IX, and XII). • The disorder causes weakness and wasting of the voluntary muscles. • Weakness is often more severe in the legs than in the arms.

5. SMA 5q: General Features

6. SMA • SMA is the second most common autosomal recessive disease in the US after cystic fibrosis. • Incidence: • Type 1: 1 per 10,000 live births • Types II and III: 1 per 24,000 births • SMA types I and III each account for about one fourth of cases, whereas SMA type II is the largest group and accounts for one half of all cases • Worldwide 7.8-10 cases per 100,000 live births • ? M:F predominance or M>F • No ethnic predominance.

7. SMA • The genetic defects associated with SMA types I-III are localized on chromosome 5q11.2-13.3. • Mutations in the SMN gene result in a loss of function of the SMN protein. • Many classification systems based on inheritance, clinical, and genetic criteria. • International SMA Consortium (ISMAC, 1994) systems is the most common.

9. SMA Type 1 • SMA type I, (Werdnig-Hoffmann acute infantile, non-sitters), occur birth – 6 months (95% by 3 months) • Severe, progressive muscle weakness and flaccid or reduced muscle tone (hypotonia). • Bulbar dysfunction includes poor suck ability, reduced swallowing, and respiratory failure. • Patients have no involvement of the extraocular muscles, and facial weakness is often minimal or absent. • They have no evidence of cerebral involvement, and infants appear alert.

10. SMA Type 1 • Impaired fetal movements are observed in 30% of cases • 60% of infants with SMA type I are floppy babies at birth. Prolonged cyanosis may be noted at delivery. • In some instances, the disease can cause fulminant weakness in the first few days of life. Such severe weakness and early bulbar dysfunction -> mean survival of 5.9 months. • Affected children never sit or stand. • In 95% of cases, infants die from complications of the disease by 18 months.

13. SMA Type 2 • SMA type II (chronic infantile, sitters) usually begin between 6 - 18 months. • Most common form of SMA • Most common manifestation is developmental motor delay. Infants with SMA type II often have difficulties with sitting independently or failure to stand by 1 year of age. • These children may learn to sit but will never be able to stand or walk.

14. SMA Type 2 • An unusual feature of the disease is a postural tremor affecting the fingers. This is thought to be related to fasciculations in the skeletal muscles • Pseudohypertrophy of the gastrocnemius muscle, musculoskeletal deformities, and respiratory failure can occur. • The lifespan of patients with SMA type II varies from 2 years to the third decade of life. Respiratory infections account for most deaths.

17. SMA Type 3 • SMA type III (Kugelberg-Welander, chronic juvenile, walkers) appear 18 months – adult. • Slowly progressive proximal weakness. Most can stand and walk but have trouble with motor skills, such as going up and down stairs. • Bulbar dysfunction occurs late in the disease. • Patients may show evidence of pseudohypertrophy. • The disease progresses slowly, and the overall course is mild. Many patients have normal life expectancies.

19. SMA • Kennedy syndrome or progressive spinobulbar muscular atrophy may occur between 15 and 60 years of age. Features of this type may include weakness of muscles in the tongue and face, difficulty swallowing, speech impairment, and excessive development of the mammary glands in males. The course of the disorder is usually slowly progressive. Kennedy syndrome is an X-linked recessive disorder, which means that women carry the gene, but the disorder only occurs in men.

20. Bulbo-Spinal Muscular Atrophy (BSMA; Kennedy's Syndrome; X-linked)

21. SMA • Congenital SMA with arthrogryposis (persistent contracture of joints with fixed abnormal posture of the limb) is a rare disorder. Manifestations include severe contractures, curvature of the spine, chest deformity, respiratory problems, an unusually small jaw, and drooping upper eyelids.

23. Pulmonary Needs • Is NOT Duchenne’s Muscular Dystophy • Diaphragm NOT involved and IS the primary muscle of breathing • Diaphragm function better when flat or in Trendelenburg • Intercostals are weak/ineffective • Chest wall compliance is increased -> chest wall shape changes (pulled down chest appearance) -> then decreases

24. Pulmonary Needs • Pulmonary compliance increases then decreases • Hypoventilation • Oxygen therapy does not address hypoventilation • Non-invasive positive pressure ventilation (NIPPV) – BiPAP NOT CPAP or non-invasive volume ventilator

25. NIPPV Goals • From Mehta and Hill • Short – term • Relieve symptoms • Reduce WOB • Improve/stabilize blood gas • Optimize patient comfort • Good patient-ventilator synchrony • Minimize risk • Avoid intubation

26. NIPPV Goals • From Mehta and Hill • Long – term • Improve sleep duration and quality • Maximize quality of life • Enhance functional status • Prolong survival

27. NIPPV • More effective in decreasing work of breathing than CPAP or negative pressure • Increasing tidal volume -> decreases respiratory rate • More effective gas exchange • Reduces daytime PCO2 • ?resets PCO2 set point, improves microatelectasis, rests fatigued muscles

28. BiPAP • High IPAP (PIP) -> goal is ventilation NOT to overcome obstruction • Want to rest muscles/decrease WOB • Low EPAP (PEEP) -> LOW 3-6 cm H20 -> compromise ability to exhale • Spontaneous – Timed mode -> want high respiratory rate that will capture their respiratory effort and rest patient (goal patient synchrony and rest) – ex. 30 • May also overdrive them if problems with synchrony and then decrease

29. BiPAP • I – time based on patient age and respiratory rate • Rise time (speed of breath delivery) usually medium setting and on room air (at home)

30. NIPPV • Respironics Synchrony • ResMed VPAP III • Puritan Bennett • Need appropriate interface • Heated or pass-over cool mist humidification

31. Non-invasive Ventilator • Pressure versus volume NO difference on outcomes • Volume – breaths on demand during day • Usually tidal volume 13-20 ml/kg/on nasal mask

32. Intubated • Extubate to BiPAP settings • Do NOT wean to low rates or T-piece • Extubate when already on room air so not to mask atelectasis with supplemental oxygen

33. Respiratory Aids • Cough Assist • Chest physiotherapy • IPV • Home suction • Pulse oximeter • Ambubag • Nebulizer • ?bronchodilators, mucolytics, anticholinergics • Gtube and Nissen fundoplication

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35. Conventional [Top] 1. Oxygen administrated arbitrarily in concentrations that maintain SaO2 well above 95%. 2. Frequent airway suctioning via the tube. 3. Supplemental oxygen increased when desaturations occur. 4. Ventilator weaning attempted at the expense of hypercapnia. 5. Extubation not attempted unless the patient appears to be ventilator weaned. 6. Extubation to CPAP or low span bi-level positive airway pressure and continued oxygen therapy. 7. Deep airway suctioning by catheterizing the upper airway along with postural drainage and chest physical therapy. 8. With increasing CO2 retention or hypoxia supplemental oxygen is increased and ultimately the patient is reintubated. 9. Following re-intubation tracheostomy is thought to be the only long-term option ...or following successful extubation bronchodilators and ongoing routine chest physical therapy are used. 10. Eventually discharged home with a tracheostomy, often following a rehabilitation stay for family training.  

36. Protocol [Top] 1. Oxygen administration limited only to approach 95% SaO2. 2. Mechanical insufflation-exsufflation used via the tube at 25 to 40 cm H2O to -25 to -40 cm H2O pressures up to every 10 minutes as needed to reverse oxyhemoglobin desaturations due to airway mucus accumulation and when there is auscultatory evidence of secretion accumulation. Abdominal thrusts are applied during exsufflation. Tube and upper airway are suctioned following use of expiratory aids as needed. 3. Expiratory aids used when desaturations occur. 4. Ventilator weaning attempted without permitting hypercapnia. 5. Extubation attempted whether or not the patient is ventilator weaned when meeting the following: A. Afebrile B. No supplemental oxygen requirement to maintain SaO2 >94% C. Chest radiograph abnormalities cleared or clearing D. Any respiratory depressants discontinued E. Airway suctioning required less than 1-2x/eight hours

37. F. Coryza diminished sufficiently so that suctioning of the nasal orifices is required less than once every 6 hours (important to facilitate use of nasal prongs/mask for post-extubation nasal ventilation) 6. Extubation to continuous nasal ventilation and no supplemental oxygen. 7. Oximetry feedback used to guide the use of expiratory aids, postural drainage, and chest physical therapy to reverse any desaturations due to airway mucus accumulation. 8. With CO2 retention or ventilator synchronization difficulties nasal interface leaks were eliminated, pressure support and ventilator rate increased or the patient switched from BiPAP-ST™ to using a volume cycled ventilator. Persistent oxyhemoglobin desaturation despite eucapnia and aggressive use of expiratory aids indicated impending respiratory distress and need to re-intubate. 9. Following re-intubation the protocol was used for a second trial of extubation to nasal ventilation ...or following successful extubation bronchodilators and chest physical therapy were discontinued and the patient weaned to nocturnal nasal ventilation. 10. Discharge home after the SaO2 remained within normal limits for 2 days and when assisted coughing was needed for less than 4 times per day.

38. Mary Schroth, MD Associate Professor UW Hospital - Clinical Science CenterOffice Suite K4/942Office: (608) 263-8555 Email: mschroth@wisc.edu View Dr. Mary Schroth's Full CV