class lecture MYASTHENIA GRAVIS

MYASTHENIA GRAVIS : 

MYASTHENIA GRAVIS Myasthenia gravis (MG) is a rare autoimmune disease. It is a disorder of neuromuscular function thought to be due to the presence of antibodies to acetylcholine receptors at the neuromuscular junction

SYMPTOMS : 

SYMPTOMS Drooping of the eyelids Double vision Difficulty smiling, speaking, swallowing Difficulty raising the arms Difficulty walking Difficulty breathing if chest muscle are affected

Pathogenesis : 

Pathogenesis 1) In MG, underlying defect is a decrease in the number of available acetylcholine receptors (AChR) at postsynaptic muscle membrane 2) Postsynaptic folds are flattened or “simplified”, causing less efficient neuromuscular transmission

Diagnosis : 

Diagnosis History and Physical “Tensilon Test” Repetitive Nerve Stimulation AChR antibody testing Single Fiber EMG

History and Physical : 

History and Physical Diplopia, ptosis Fatigability Reduced strength on exam Reduced vital capacity

Tensilon Test : 

Tensilon Test Edrophonium is an AChE inhibitor Rapid onset (30s) and short duration of action (about 5 minutes) Focus on a weak muscle group and evaluate. Initial dose of 2mg given I.V. If no change, give additional 8mg I.V.

AChR Antibodies : 

AChR Antibodies Measured level does NOT correspond well with severity of disease In an individual patient, however, treatment-induced fall in the antibody level often correlates with clinical improvement

Treatment : 

Treatment AChE inhibitors Pyridostigmine (Mestinon) Immunosuppression Rapid immunomodulating treatments Plasma exchange Thymectomy

AChE inhibitors : 

AChE inhibitors Neostigmine Treatment start with this drug. 15 mg orally, 6 hourly. Dose is adjusted according to the response. Alternative drug Pyridostigmine (Mestinon) Effect starts in 15-30 minutes, lasts 3-4 hours Titrate dosage to symptoms Cholinergic symptoms can limit use

Plasmapheresis : 

Plasmapheresis Plasmapheresis Pathogenic antibodies removed Usually a course of 5 exchanges over a 2 week period Useful for temporary relief of symptoms

Immunosuppression : 

Immunosuppression Glucocorticoids inhibit 1) production of NR-antibodies 2) increase synthesis of NRs. Immunosuppressant (Azathioprine, cyclosporin) Inhibit NR-antibodies synthesis by affecting T-cells Glucocorticoids and cyclosporin generally produce improvement within 1-3 months Azathioprine and mycophenolate take up to a year to show effect

Thymectomy : 

Thymectomy Thymus has modified musle cells having NRs which is a source of antigen for the production of anti-NR antibodies in MG. In the absence of tumor, 85% of patients have improvement after thymectomy Improvement takes months to years