Neuromuscular Diseases

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


<ul><li> 1. Neuromuscular Diseases Roy Maynard, M.D. September 23, 2010 </li> <li> 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 </li> <li> 3. Classification Muscular Dystrophies Congenital and Metabolic Myopathies Anterior Horn Cell Disorders Neuromuscular Junction Diseases 3 of 56 </li> <li> 4. Epidemiology of Neuromuscular Diseases Accessed on September 14, 2010 4 of 56 </li> <li> 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 </li> <li> 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 </li> <li> 7. Clinical Symptoms of Impending Respiratory Failure Infants Paradoxical breathing Tachypnea Head bobbing Poor feeding Increasing muscle weakness and hypotonia 7 of 56 </li> <li> 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 </li> <li> 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 </li> <li> 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 </li> <li> 11. Duchenne Muscular Dystrophy Accessed on September 20, 2010 11 of 56 </li> <li> 12. Duchenne Muscular Dystrophy Accessed 9/20/10 12 of 56 </li> <li> 13. Classification: Congenital Myopathies Nemaline myopathy Myotubular/Centronuclear myopathy Central core disease Multiminicore disease Congenital fiber-type disproportion myopathy 13 of 56 </li> <li> 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 </li> <li> 15. Nemaline Myopathy Accessed 9/20/10 15 of 56 </li> <li> 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 </li> <li> 17. Myotubular Myopathy Accessed 9/20/10 17 of 56 </li> <li> 18. Myotubular Myopathy Accessed 9/20/10 18 of 56 </li> <li> 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 </li> <li> 20. Central Core Disease Accessed 9/20/10 20 of 56 </li> <li> 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 </li> <li> 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 </li> <li> 23. Newborn with Hypotonia Accessed 9/20/10 23 of 56 </li> <li> 24. Multiminicore Disease Myopathy Accessed 9/20/10 24 of 56 </li> <li> 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 </li> <li> 26. Congenital Fiber-Type Disproportion Accessed 9/20/10 26 of 56 </li> <li> 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 </li> <li> 28. Classification: Anterior Horn Cell Disorders Infectious - poliomyelitis Motor neuron disease - amyotrophic lateral sclerosis Spinal muscular atrophy (SMA) 28 of 56 </li> <li> 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 </li> <li> 30. SMA Types Type 1 Type 2 Type 3 Type 4 Non-5q-SMAs 30 of 56 </li> <li> 31. Incidence SMA at Birth 12% Type 1 27% 60% Type 2 Type 3 31 of 56 </li> <li> 32. Prevalence SMA in Population 14% 35% Type 1 Type 2 Type 3 51% 32 of 56 </li> <li> 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 &lt; 2 years 33 of 56 </li> <li> 34. SMA Type 1 Accessed 9/20/10 34 of 56 </li> <li> 35. SMA Type 2 Intermediate severity Age of onset 7-18 months Sits but never stands Life expectancy &gt; 2 years 35 of 56 </li> <li> 36. SMA Types 3 and 4 SMA 3 Kugelberg-Welander Disease Mild severity Age of onset &gt; 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 </li> <li> 37. Anterior Horn Cell Disease Accessed 9/20/10 37 of 56 </li> <li> 38. Anterior Horn Cell Disease Accessed 9/20/10 38 of 56 </li> <li> 39. Anterior Horn Cell Disease and Accessed both websites 9/20/10 39 of 56 </li> <li> 40. Classification:Diseases of the Neuromuscular Junction Congenital myasthenic syndromes Myasthenia gravis Acetylcholine junction 40 of 56 </li> <li> 41. Pathophysiology of Myasthenia Gravis Accessed 9/20/10 41 of 56 </li> <li> 42. Congenital Myastheinic Syndromes Presynaptic insufficient acetylcholine Postsynaptic receptor problem Synaptic acetylcholinesterase deficiency Accessed 9/20/10 42 of 56 </li> <li> 43. Complications of Neuromuscular Disease Scoliosis Bulbar Dysfunction Swallowing dysfunction, speech Osteoporosis Respiratory Failure Cardiomyopathy/Congestive Heart Failure Early Death 43 of 56 </li> <li> 44. Monitoring for Respiratory Failure Serial monitoring of lung function when able to be performed (&gt; 5 years of age) FVC &lt; 1 liter Close monitoring, consider NIV FVC &lt; 40% of predicted (nocturnal hypoventilation) Refer for polysomnography MIP &lt; 40 cm H2O MEP &lt; 45 cm H2O Polysomnography, consider day/night CO2 Peak Cough Flows &lt; 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...</li></ul>


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