MYASTHENIA GRAVIS (MG)

CASE STUDY 66 year male Physical exam revealed Ice pack test Healthy and active entire life Presents with 4 month history of gradually progressive diplopia Physical exam revealed Moderate ptosis of both eyelids Limitation of R/L ocular movement Ice pack test Improved ptosis

CASE STUDY Radiology Laboratory CT of chest was normal Tests Results ANA Negative RF Negative Anti-AChR Positive Anti-MuSK Negative

CASE STUDY Prescription for pyridostigmine (Mestinon) 6 tablets (60 mg) daily Dose reduced to 3 tablets daily Nausea, vomiting and diarrhea Two years later following severe influenza Diplopia, dysphagia, dysarthria, dyspnea Admitted to hospital and treated with Azathioprine (Imuran)

MYASTHENIA GRAVIS (MG) Chronic autoimmune neuromuscular disease Hallmark Skeletal muscle weakness and fatigue Increases with activity and improves with rest Muscles affected Eye and eyelid movement, facial expression, chewing, swallowing and talking Most common primary disease of neuromuscular transmission

EPIDEMIOLOGY OF MYASTHENIA GRAVIS Prevalence of 50,000 cases in US All ethnic groups and both genders Female to male ratio 20 to 40 years (females 1.5:1) 50 to 70 years (males 1.5:1) Etiology is unknown

SYMPTOMS OF MYASTHENIA GRAVIS Ptosis Diplopia Dysphagia Dysarthria Change in facial expression Weakness of arms, hands, fingers, legs

DIAGNOSIS OF MYASTHENIA GRAVIS Physical examination for muscle fatigue Edrophonium Test IV administration of Edrophonium chloride (Tensilon) Blocks degradation of acetylcholine Brief relief of eye weakness Single fiber electromyography (EMG) CT of thymus gland

LABORATORY DIAGNOSIS OF MG Acetylcholine receptor antibody (Anti-AChR) Binding Blocking Modulating Muscle-specific tyrosine kinase antibody Anti-MuSK 45% of seronegative MG

LABORATORY DIAGNOSIS OF MG Acetylcholine receptor antibody, binding 90% generalized 70% ocular Acetylcholine receptor antibody, blocking 50% generalized 20% ocular Acetylcholine receptor antibody, modulating

IMMUNOPATHOLOGY OF MYASTHENIA GRAVIS Type II autoimmune mechanism Autoantibody (antagonistic) for acetylcholine receptor at post-synaptic neuromuscular junction Acetylcholine receptors are Blocked Altered Destroyed Muscle contraction is prevented

IMMUNOPATHOLOGY OF MYASTHENIA GRAVIS Role of thymus gland is unclear 75% of patients have thymus abnormality 85% thymic hyperplasia 15% thyroma Disease usually more severe with thyroma

TREATMENT OF MYASTHENIA GRAVIS Anticholinesterase agents Neostigmine (Prostigmin) Pyridostigmine (Mestinon) Corticosteroids / Immunosuppressive agents Prednisone Azathioprine Intravenous Immunoglobulin (IVIG) Thymectomy Plasmapheresis (plasma exchange)