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

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

Synaptic antigens nerve muscle VGCC MuSK AChR

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

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

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

Low frequency stimulation - decrement

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

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

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

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

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

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