Transcript Myasthenia Gravis

MYASTHENIA GRAVIS
(MG)
CASE STUDY
• 66 year male
> 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
> CT of chest was normal
• Laboratory
> Tests
– ANA
– RF
– Anti-AChR
– Anti-MuSK
Results
Negative
Negative
Positive
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
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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
> 90% generalized
> 70% ocular
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)