56
Neuromuscular Diseases Roy Maynard, M.D. September 23, 2010

Neuromuscular Diseases

Embed Size (px)

DESCRIPTION

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

Citation preview

Page 1: Neuromuscular Diseases

Neuromuscular Diseases Roy Maynard, M.D. September 23, 2010

Page 2: Neuromuscular Diseases

2 of 56

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

Page 3: Neuromuscular Diseases

3 of 56

Classification

• Muscular Dystrophies • Congenital and Metabolic Myopathies • Anterior Horn Cell Disorders • Neuromuscular Junction Diseases

Page 4: Neuromuscular Diseases

4 of 56

Epidemiology of Neuromuscular Diseases

http://www.mfm-nmd.org/history.aspx Accessed on September 14, 2010

Page 5: Neuromuscular Diseases

5 of 56

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

Page 6: Neuromuscular Diseases

6 of 56

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

Page 7: Neuromuscular Diseases

7 of 56

Clinical Symptoms of Impending Respiratory Failure

• Infants – Paradoxical breathing – Tachypnea – Head bobbing – Poor feeding – Increasing muscle weakness and hypotonia

Page 8: Neuromuscular Diseases

8 of 56

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

Page 9: Neuromuscular Diseases

9 of 56

Classification: Muscular Dystrophies

– Duchenne muscular dystrophy – Becker muscular dystrophy – Myotonic muscular dystrophy – Congenital muscular dystrophy (8) – Distal muscular dystrophy (8) – Others

Page 10: Neuromuscular Diseases

10 of 56

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

Page 12: Neuromuscular Diseases

12 of 56

Duchenne Muscular Dystrophy

http://www.humgen.nl/lab-vdeutekom/pictures/DGC.jpg Accessed 9/20/10

Page 13: Neuromuscular Diseases

13 of 56

Classification: Congenital Myopathies

• Nemaline myopathy • Myotubular/Centronuclear myopathy • Central core disease • Multiminicore disease • Congenital fiber-type disproportion

myopathy

Page 14: Neuromuscular Diseases

14 of 56

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

Page 15: Neuromuscular Diseases

15 of 56

Nemaline Myopathy

http://www.childrenshospital.org/cfapps/research/data_admin/Site1694/Images/S93-1497EM25039_490px.jpg Accessed 9/20/10

Page 16: Neuromuscular Diseases

16 of 56

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

Page 17: Neuromuscular Diseases

17 of 56

Myotubular Myopathy

http://www.mtmrg.org/MTM%20Article%20by%20CR.PDF Accessed 9/20/10

Page 18: Neuromuscular Diseases

18 of 56

Myotubular Myopathy

http://www.mtmrg.org/MTM%20Article%20by%20CR.PDF Accessed 9/20/10

Page 19: Neuromuscular Diseases

19 of 56

Central Core Disease

• Proximal skeletal muscles • Variable clinical picture • Malignant hyperthermia • Rare • Mutations RYR1 gene • Genetics autosomal dominant (some

autosomal recessive)

Page 20: Neuromuscular Diseases

20 of 56

Central Core Disease

http://www.neurologyindia.com/articles/2008/56/3/images/ni_2008_56_3_325_43451_u1.jpg Accessed 9/20/10

Page 21: Neuromuscular Diseases

21 of 56

Multiminicore Disease

• Genetics autosomal recessive – SEPPN1 mutation – Rare disease

• Clinical – 4 types

• Rigid spine (classic) • Progressive with hand involvement • Arthrogryposis multiplex • opththalmoplegic

Page 22: Neuromuscular Diseases

22 of 56

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

Page 23: Neuromuscular Diseases

23 of 56

Newborn with Hypotonia

http://neuromuscular.wustl.edu/pics/people/patients/cmdl.jpg Accessed 9/20/10

Page 24: Neuromuscular Diseases

24 of 56

Multiminicore Disease Myopathy

http://www.scielo.br/img/revistas/anp/v62n4/a02fig04.gif Accessed 9/20/10

Page 25: Neuromuscular Diseases

25 of 56

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

Page 26: Neuromuscular Diseases

26 of 56

Congenital Fiber-Type Disproportion

http://brain.oxfordjournals.org/content/vol128/issue7/images/large/awh511f5.jpeg Accessed 9/20/10

Page 27: Neuromuscular Diseases

27 of 56

Metabolic Myopathies

• Pompe disease • Phosphorylase deficiency • Phosphofructokinase deficiency • Debrancher enzyme deficiency • Mitochondrial myopathy • Carnitine deficiency • Carnitine palmityl transferase deficiency • Lactate dehydrogenase deficiency • Others

Page 28: Neuromuscular Diseases

28 of 56

Classification: Anterior Horn Cell Disorders

• Infectious - poliomyelitis • Motor neuron disease - amyotrophic

lateral sclerosis • Spinal muscular atrophy (SMA)

Page 29: Neuromuscular Diseases

29 of 56

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

Page 30: Neuromuscular Diseases

30 of 56

SMA Types

• Type 1 • Type 2 • Type 3 • Type 4 • Non-5q-SMA’s

Page 31: Neuromuscular Diseases

31 of 56

Incidence SMA at Birth

Type 1Type 2Type 3

60%

12%

27%

Page 32: Neuromuscular Diseases

32 of 56

Prevalence SMA in Population

Type 1Type 2Type 3

51%

14%

35%

Page 33: Neuromuscular Diseases

33 of 56

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

Page 34: Neuromuscular Diseases

34 of 56

SMA Type 1

http://www.kierahenry.com/i//tn2_1.jpg Accessed 9/20/10

Page 35: Neuromuscular Diseases

35 of 56

SMA Type 2

• Intermediate severity • Age of onset 7-18 months • Sits but never stands • Life expectancy > 2 years

Page 36: Neuromuscular Diseases

36 of 56

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

Page 38: Neuromuscular Diseases

38 of 56

Anterior Horn Cell Disease

http://www.ott.zynet.co.uk/polio/lincolnshire/library/gawne/images/pandcmfig3.gif Accessed 9/20/10

Page 39: Neuromuscular Diseases

39 of 56

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

Page 40: Neuromuscular Diseases

40 of 56

Classification: Diseases of the Neuromuscular Junction

• Congenital myasthenic syndromes • Myasthenia gravis

– Acetylcholine junction

Page 41: Neuromuscular Diseases

41 of 56

http://jama.ama-assn.org/content/vol293/issue15/images/medium/jpg0420f1.jpg Accessed 9/20/10

Pathophysiology of Myasthenia Gravis

Page 42: Neuromuscular Diseases

42 of 56

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

Page 43: Neuromuscular Diseases

43 of 56

Complications of Neuromuscular Disease

• Scoliosis • Bulbar Dysfunction

– Swallowing dysfunction, speech

• Osteoporosis • Respiratory Failure • Cardiomyopathy/Congestive Heart

Failure • Early Death

Page 44: Neuromuscular Diseases

44 of 56

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

Page 45: Neuromuscular Diseases

45 of 56

Diagnostic Studies

• Polysomnography – Upper airway obstruction

• Blood gases • Cardiac Echo • Serial pulmonary function tests

Page 46: Neuromuscular Diseases

46 of 56

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

Page 47: Neuromuscular Diseases

47 of 56

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

Page 48: Neuromuscular Diseases

48 of 56

Negative Pressure Ventilation

http://www.ispub.com/ispub/ijh/volume_3_number_2_21/intensive_care_unit/icu-fig2a.jpg Accessed 9/20/10

Page 49: Neuromuscular Diseases

49 of 56

Negative Pressure Ventilation

http://nivusers.tripod.com/Equipic/Negvent.html Accessed 9/20/10

Page 51: Neuromuscular Diseases

51 of 56

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

Page 52: Neuromuscular Diseases

52 of 56

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

Page 55: Neuromuscular Diseases

55 of 56

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

Page 56: Neuromuscular Diseases

56 of 56

Q&A

Thank you for attending!