Disorders of the Neuromuscular JunctionDisorders of the Neuromuscular Junction

Myasthenia gravisMyasthenia gravis

Radim Mazanec, MD, PhDRadim Mazanec, MD, PhD

DefinitionDefinition

An autoimmune disease due to an antibody An autoimmune disease due to an antibody mediated attack directed against nicotinic mediated attack directed against nicotinic AchR at neuromuscular junctionAchR at neuromuscular junction

10% have thymoma10% have thymoma 70% have thymic hyperplasia70% have thymic hyperplasia

5

Synaptic aSynaptic antigenntigenss

nerve

muscle

VGCC

AChRMuSK

EpidemiologyEpidemiology

Incidence 1 : 20 000 in USAIncidence 1 : 20 000 in USA

Women slightly higher incidence 3 : 2Women slightly higher incidence 3 : 2 Majority of the MG are young women in Majority of the MG are young women in

the third decade and middle aged men in the third decade and middle aged men in 5th and 6th decade5th and 6th decade

Children account for 11% of all patients Children account for 11% of all patients with MGwith MG

Clinical FeaturesClinical Features

Fluctuated muscle weakness and excessive Fluctuated muscle weakness and excessive fatiguabilityfatiguability

Diplopia and ptosisDiplopia and ptosis Bulbar weakness – swalloving, dysarthriaBulbar weakness – swalloving, dysarthria Generalized weakness of the trunk and Generalized weakness of the trunk and

extremitiesextremities

Diagnostic algorhitmDiagnostic algorhitm

ElectromyographyElectromyography

AChR antibodiesAChR antibodies

MR of mediastinum – thymomas, hyperplasiaMR of mediastinum – thymomas, hyperplasia

Low frequency stimulation - Low frequency stimulation - decrementdecrement

TreatmentTreatment

ThymectomyThymectomy

Plasma exchange in myasthenic crisis (TPE)Plasma exchange in myasthenic crisis (TPE)

Human immune globuline (IvIg)Human immune globuline (IvIg)

Corticosteroids + cytostaticsCorticosteroids + cytostatics

AChE inhibitors (pyridostigmine, distigmine)AChE inhibitors (pyridostigmine, distigmine)

Myasthenic crisisMyasthenic crisis

Respiratory insuficiency – paralysis of Respiratory insuficiency – paralysis of respiratory musclesrespiratory muscles

Assisted ventilation requiredAssisted ventilation required

Affect 15-20% myasthenic patientsAffect 15-20% myasthenic patients Females : males = 2 : 1Females : males = 2 : 1 Average age : 55 yearsAverage age : 55 years

Clinical featuresClinical features

Respiratory tract infection, pneumonia ( 38%)Respiratory tract infection, pneumonia ( 38%)

Respiratory failure 99%Respiratory failure 99%

Oropharyngeal or ocular weakness 86%Oropharyngeal or ocular weakness 86%

Arms and legs weakness 76%Arms and legs weakness 76%

Complication of crisisComplication of crisis

Ateletactic pneumonia (40%)Ateletactic pneumonia (40%)

HypotensionHypotension

Cardio-respiratory arrestCardio-respiratory arrest

Pneumothorax Pneumothorax

Treatment Treatment

ICU is required for assisted ventilationICU is required for assisted ventilation Cardiopulmonary monitoringCardiopulmonary monitoring

Plasmapheresis ( 5 sessions) or IvIg 2g/kg Plasmapheresis ( 5 sessions) or IvIg 2g/kg in five consecutive daysin five consecutive days

Antithrombotic treatmentAntithrombotic treatment Antibiotics Antibiotics Respiratory rehabilitationRespiratory rehabilitation

OutcomeOutcome

Duration of intubation : 13 daysDuration of intubation : 13 days Duration of hospitalization : 35 daysDuration of hospitalization : 35 days

Tracheostomy cca 40%Tracheostomy cca 40% Mortality cca 4% Mortality cca 4%