Neuromuscular Diseases

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Dr. Maynard's outline on neuromuscular disorders (presented on 9/23/10).

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Neuromuscular Diseases

  1. 1. Neuromuscular Diseases Roy Maynard, M.D. September 23, 2010
  2. 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
  3. 3. Classification• Muscular Dystrophies• Congenital and Metabolic Myopathies• Anterior Horn Cell Disorders• Neuromuscular Junction Diseases 3 of 56
  4. 4. Epidemiology of Neuromuscular Diseases http://www.mfm-nmd.org/history.aspx Accessed on September 14, 2010 4 of 56
  5. 5. Clinical Signs of Neuromuscular Disease• Weakness, poor cough, retained airway secretions• Inability to lift extremities against gravity• Muscle wasting• Low muscle tone (hypotonia)• Poor feeding, swallowing dysfunction• Failure to thrive• Increased respiratory rate• Use of accessory muscles of respiration• Recurrent infections• Night sweats 5 of 56
  6. 6. Work-Up Hypotonia and Weakness • CK - creatinine kinase • EMG - electromyogram • NCS - nerve conduction study • ECG - cardiac muscle involvement • Muscle Biopsy - electron microscopy • Nerve Biopsy • Gene testing • Others 6 of 56
  7. 7. Clinical Symptoms of Impending Respiratory Failure• Infants – Paradoxical breathing – Tachypnea – Head bobbing – Poor feeding – Increasing muscle weakness and hypotonia 7 of 56
  8. 8. Clinical Symptoms of Impending Respiratory Failure• Older children – Sleep disordered breathing (SDB) • Daytime behavioral and neurocognitive problems • Hyperactivity • Tiredness • Morning headaches • Nocturnal arousals • Daytime sleepiness • Anorexia 8 of 56
  9. 9. Classification: Muscular Dystrophies – Duchenne muscular dystrophy – Becker muscular dystrophy – Myotonic muscular dystrophy – Congenital muscular dystrophy (8) – Distal muscular dystrophy (8) – Others 9 of 56
  10. 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. 11. Duchenne Muscular Dystrophy http://upload.wikimedia.org/wikipedia/commons/4/49/Duchenne-muscular-dystrophy.jpg Accessed on September 20, 2010 11 of 56
  12. 12. Duchenne Muscular Dystrophy http://www.humgen.nl/lab-vdeutekom/pictures/DGC.jpg Accessed 9/20/10 12 of 56
  13. 13. Classification: Congenital Myopathies • Nemaline myopathy • Myotubular/Centronuclear myopathy • Central core disease • Multiminicore disease • Congenital fiber-type disproportion myopathy 13 of 56
  14. 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
  15. 15. Nemaline Myopathyhttp://www.childrenshospital.org/cfapps/research/data_admin/Site1694/Images/S93-1497EM25039_490px.jpg Accessed 9/20/10 15 of 56
  16. 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. 17. Myotubular Myopathy http://www.mtmrg.org/MTM%20Article%20by%20CR.PDF Accessed 9/20/10 17 of 56
  18. 18. Myotubular Myopathy http://www.mtmrg.org/MTM%20Article%20by%20CR.PDF Accessed 9/20/10 18 of 56
  19. 19. Central Core Disease• Proximal skeletal muscles• Variable clinical picture• Malignant hyperthermia• Rare• Mutations RYR1 gene• Genetics autosomal dominant (some autosomal recessive) 19 of 56
  20. 20. Central Core Diseasehttp://www.neurologyindia.com/articles/2008/56/3/images/ni_2008_56_3_325_43451_u1.jpg Accessed 9/20/10 20 of 56
  21. 21. Multiminicore Disease• Genetics autosomal recessive – SEPPN1 mutation – Rare disease• Clinical – 4 types • Rigid spine (classic) • Progressive with hand involvement • Arthrogryposis multiplex • opththalmoplegic 21 of 56
  22. 22. Multiminicore Disease• Symptoms – Muscle weakness and wasting – Scoliosis – Impaired respiratory function – Delayed motor development – Feeding problems in infants – Contractures – Weak eye movements – Low set ears• Management – Supportive 22 of 56
  23. 23. Newborn with Hypotonia http://neuromuscular.wustl.edu/pics/people/patients/cmdl.jpg Accessed 9/20/10 23 of 56
  24. 24. Multiminicore Disease Myopathy http://www.scielo.br/img/revistas/anp/v62n4/a02fig04.gif Accessed 9/20/10 24 of 56
  25. 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. 26. Congenital Fiber-Type Disproportion http://brain.oxfordjournals.org/content/vol128/issue7/images/large/awh511f5.jpeg Accessed 9/20/10 26 of 56
  27. 27. Metabolic Myopathies• Pompe disease• Phosphorylase deficiency• Phosphofructokinase deficiency• Debrancher enzyme deficiency• Mitochondrial myopathy• Carnitine deficiency• Carnitine palmityl transferase deficiency• Lactate dehydrogenase deficiency• Others 27 of 56
  28. 28. Classification: Anterior Horn Cell Disorders • Infectious - poliomyelitis • Motor neuron disease - amyotrophic lateral sclerosis • Spinal muscular atrophy (SMA) 28 of 56
  29. 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. 30. SMA Types• Type 1• Type 2• Type 3• Type 4• Non-5q-SMA’s 30 of 56
  31. 31. Incidence SMA at Birth 12% Type 1 27% 60% Type 2 Type 3 31 of 56
  32. 32. Prevalence SMA in Population 14% 35% Type 1 Type 2 Type 3 51% 32 of 56
  33. 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
  34. 34. SMA Type 1http://www.kierahenry.com/i//tn2_1.jpg Accessed 9/20/10 34 of 56
  35. 35. SMA Type 2• Intermediate severity• Age of onset 7-18 months• Sits but never stands• Life expectancy > 2 years 35 of 56
  36. 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
  37. 37. Anterior Horn Cell Disease http://www.alsont.ca/_media/Image/about-als/als-diagram.jpg Accessed 9/20/10 37 of 56
  38. 38. Anterior Horn Cell Disease http://www.ott.zynet.co.uk/polio/lincolnshire/library/gawne/images/pandcmfig3.gif Accessed 9/20/10 38 of 56
  39. 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. 40. Classification:Diseases of the Neuromuscular Junction • Congenital myasthenic syndromes • Myasthenia gravis – Acetylcholine junction 40 of 56
  41. 41. Pathophysiology of Myasthenia Gravis http://jama.ama-assn.org/content/vol293/issue15/images/medium/jpg0420f1.jpg Accessed 9/20/10 41 of 56
  42. 42. Congenital Myastheinic Syndromes • Presynaptic insufficient acetylcholine • Postsynaptic receptor problem • Synaptic acetylcholinesterase deficiency http://www.med.nagoya-u.ac.jp/imgs04/i4l02m11mp1d310007_3.jpg Accessed 9/20/10 42 of 56
  43. 43. Complications of Neuromuscular Disease• Scoliosis• Bulbar Dysfunction – Swallowing dysfunction, speech• Osteoporosis• Respiratory Failure• Cardiomyopathy/Congestive Heart Failure• Early Death 43 of 56
  44. 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
  45. 45. Diagnostic Studies• Polysomnography – Upper airway obstruction• Blood gases• Cardiac Echo• Serial pulmonary function tests 45 of 56
  46. 46. Physiology of Respiratory Pump Failure • Infants highly compliant chest • Hypopnea • Low tidal volumes (scoliosis impairs) • Decreased FRC • Early airway closure and atelectasis • Mechanical disadvantage • Poor collateral ventilation • Respiratory muscles change with time • Decreased chest wall movement • Impaired cough 46 of 56
  47. 47. Interventions• Adenotonsillectomy• Limited care• Non-invasive ventilation – High flow nasal cannula, sipap – Sip and puff, insufflation/exsufflation – Cpap face or nasal – Bipap face or nasal – Negative pressure ventilation• Invasive ventilation – Trach 47 of 56
  48. 48. Negative Pressure Ventilation http://www.ispub.com/ispub/ijh/volume_3_number_2_21/intensive_care_unit/icu-fig2a.jpg Accessed 9/20/10 48 of 56
  49. 49. Negative Pressure Ventilation http://nivusers.tripod.com/Equipic/Negvent.html Accessed 9/20/10 49 of 56
  50. 50. Invasive Respiratory Supporthttp://upload.wikimedia.org/wikipedia/commons/thumb/9/94/VIP_Bird2.jpg/300px-VIP_Bird2.jpg Accessed 9/20/10 50 of 56
  51. 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. 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
  53. 53. Non-Invasive Ventilation http://thevibe.socialvibe.com/wp-content/uploads/2008/07/photo-764404.jpg Accessed 9/20/10 53 of 56
  54. 54. Non-Invasive Ventilation http://www.mda.org/publications/images/q11-3_Taleah_English-SMA.jpg Accessed 9/20/10 54 of 56
  55. 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
  56. 56. Q&AThank you for attending! 56 of 56

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