MYASTHENIA GRAVIS MYASTHENIA GRAVIS (MG)(MG)

CASE STUDYCASE STUDY

• 66 year male 66 year male > Healthy and active entire lifeHealthy and active entire life> Presents with 4 month history of gradually progressive diplopiaPresents with 4 month history of gradually progressive diplopia

• Physical exam revealed Physical exam revealed > Moderate ptosis of both eyelidsModerate ptosis of both eyelids> Limitation of R/L ocular movementLimitation of R/L ocular movement

• Ice pack testIce pack test> Improved ptosisImproved ptosis

CASE STUDYCASE STUDY

• RadiologyRadiology> CT of chest was normalCT of chest was normal

• LaboratoryLaboratory> Tests ResultsTests Results

– ANA ANA NegativeNegative– RF RF NegativeNegative– Anti-AChR Anti-AChR PositivePositive– Anti-MuSK Anti-MuSK NegativeNegative

CASE STUDYCASE STUDY

• Prescription for pyridostigmine (Mestinon)Prescription for pyridostigmine (Mestinon)> 6 tablets (60 mg) daily6 tablets (60 mg) daily

• Dose reduced to 3 tablets dailyDose reduced to 3 tablets daily> Nausea, vomiting and diarrheaNausea, vomiting and diarrhea

• Two years later following severe influenzaTwo years later following severe influenza> Diplopia, dysphagia, dysarthria, dyspneaDiplopia, dysphagia, dysarthria, dyspnea

• Admitted to hospital and treated withAdmitted to hospital and treated with> Azathioprine (Imuran)Azathioprine (Imuran)

MYASTHENIA GRAVIS (MG)MYASTHENIA GRAVIS (MG)

• Chronic autoimmune neuromuscular diseaseChronic autoimmune neuromuscular disease

• HallmarkHallmark> Skeletal muscle weakness and fatigueSkeletal muscle weakness and fatigue> Increases with activity and improves with restIncreases with activity and improves with rest

• Muscles affectedMuscles affected> Eye and eyelid movement, facial expression, chewing, swallowing and talkingEye and eyelid movement, facial expression, chewing, swallowing and talking

• Most common primary disease of neuromuscular transmissionMost common primary disease of neuromuscular transmission

EPIDEMIOLOGY OF EPIDEMIOLOGY OF MYASTHENIA GRAVISMYASTHENIA GRAVIS

• Prevalence of 50,000 cases in USPrevalence of 50,000 cases in US

• All ethnic groups and both gendersAll ethnic groups and both genders

• Female to male ratioFemale to male ratio> 20 to 40 years (females 1.5:1)20 to 40 years (females 1.5:1)> 50 to 70 years (males 1.5:1)50 to 70 years (males 1.5:1)

• Etiology is unknownEtiology is unknown

SYMPTOMS OF SYMPTOMS OF MYASTHENIA GRAVISMYASTHENIA GRAVIS

• PtosisPtosis• DiplopiaDiplopia• DysphagiaDysphagia• DysarthriaDysarthria• Change in facial expressionChange in facial expression• Weakness of arms, hands, fingers, legsWeakness of arms, hands, fingers, legs

DIAGNOSIS OF DIAGNOSIS OF MYASTHENIA GRAVISMYASTHENIA GRAVIS

• Physical examination for muscle fatiguePhysical examination for muscle fatigue

• Edrophonium TestEdrophonium Test> IV administration of Edrophonium chloride (Tensilon)IV administration of Edrophonium chloride (Tensilon)> Blocks degradation of acetylcholineBlocks degradation of acetylcholine> Brief relief of eye weaknessBrief relief of eye weakness

• Single fiber electromyography (EMG)Single fiber electromyography (EMG)

• CT of thymus glandCT of thymus gland

LABORATORY DIAGNOSIS LABORATORY DIAGNOSIS OF MGOF MG

• Acetylcholine receptor antibody (Anti-AChR)Acetylcholine receptor antibody (Anti-AChR)> BindingBinding> BlockingBlocking> ModulatingModulating

• Muscle-specific tyrosine kinase antibodyMuscle-specific tyrosine kinase antibody> Anti-MuSKAnti-MuSK> 45% of seronegative MG45% of seronegative MG

LABORATORY DIAGNOSIS LABORATORY DIAGNOSIS OF MGOF MG

• Acetylcholine receptor antibody, bindingAcetylcholine receptor antibody, binding> 90% generalized90% generalized> 70% ocular70% ocular

• Acetylcholine receptor antibody, blockingAcetylcholine receptor antibody, blocking> 50% generalized50% generalized> 20% ocular20% ocular

• Acetylcholine receptor antibody, modulatingAcetylcholine receptor antibody, modulating> 90% generalized90% generalized> 70% ocular70% ocular

IMMUNOPATHOLOGY OF IMMUNOPATHOLOGY OF MYASTHENIA GRAVISMYASTHENIA GRAVIS

• Type II autoimmune mechanismType II autoimmune mechanism

• Autoantibody (antagonistic) for acetylcholine receptor at Autoantibody (antagonistic) for acetylcholine receptor at post-synaptic neuromuscular junctionpost-synaptic neuromuscular junction

• Acetylcholine receptors areAcetylcholine receptors are> BlockedBlocked> AlteredAltered> DestroyedDestroyed

• Muscle contraction is preventedMuscle contraction is prevented

IMMUNOPATHOLOGY OF IMMUNOPATHOLOGY OF MYASTHENIA GRAVISMYASTHENIA GRAVIS

• Role of thymus gland is unclearRole of thymus gland is unclear

• 75% of patients have thymus abnormality75% of patients have thymus abnormality> 85% thymic hyperplasia85% thymic hyperplasia> 15% thyroma15% thyroma

• Disease usually more severe with thyromaDisease usually more severe with thyroma

TREATMENT OF TREATMENT OF MYASTHENIA GRAVISMYASTHENIA GRAVIS

• Anticholinesterase agentsAnticholinesterase agents> Neostigmine (Prostigmin)Neostigmine (Prostigmin)> Pyridostigmine (Mestinon)Pyridostigmine (Mestinon)

• Corticosteroids / Immunosuppressive agentsCorticosteroids / Immunosuppressive agents> PrednisonePrednisone> AzathioprineAzathioprine

• Intravenous Immunoglobulin (IVIG)Intravenous Immunoglobulin (IVIG)

• ThymectomyThymectomy

• Plasmapheresis (plasma exchange)Plasmapheresis (plasma exchange)