Disorders of the Neuromuscular Junction

1. Disorders of the Neuromuscular Junction Myasthenia gravis Radim Mazanec, MD, PhD

2. Definition • An autoimmune disease due to an antibody mediated attack directed against nicotinic AchR at neuromuscular junction • 10% have thymoma • 70% have thymic hyperplasia

5. nerve muscle Synaptic antigens VGCC MuSK AChR

6. Epidemiology • Incidence 1 : 20 000 in USA • Women slightly higher incidence 3 : 2 • Majority of the MG are young women in the third decade and middle aged men in 5th and 6th decade • Children account for 11% of all patients with MG

7. Clinical Features • Fluctuated muscle weakness and excessive fatiguability • Diplopia and ptosis • Bulbar weakness – swalloving, dysarthria • Generalized weakness of the trunk and extremities

8. Diagnostic algorhitm • Electromyography • AChR antibodies • MR of mediastinum – thymomas, hyperplasia

9. Low frequency stimulation - decrement

10. Treatment • Thymectomy • Plasma exchange in myasthenic crisis (TPE) • Human immune globuline (IvIg) • Corticosteroids + cytostatics • AChE inhibitors (pyridostigmine, distigmine)

11. Myasthenic crisis • Respiratory insuficiency – paralysis of respiratory muscles • Assisted ventilation required • Affect 15-20% myasthenic patients • Females : males = 2 : 1 • Average age : 55 years

12. Clinical features • Respiratory tract infection, pneumonia ( 38%) • Respiratory failure 99% • Oropharyngeal or ocular weakness 86% • Arms and legs weakness 76%

13. Complication of crisis • Ateletactic pneumonia (40%) • Hypotension • Cardio-respiratory arrest • Pneumothorax

14. Treatment • ICU is required for assisted ventilation • Cardiopulmonary monitoring • Plasmapheresis ( 5 sessions) or IvIg 2g/kg in five consecutive days • Antithrombotic treatment • Antibiotics • Respiratory rehabilitation

15. Outcome • Duration of intubation : 13 days • Duration of hospitalization : 35 days • Tracheostomy cca 40% • Mortality cca 4%