MYASTHENIA GRAVIS GENERAL THORACIC SURGERY CHAPTER 168 Myasthenia gravis • A neuromuscular disorder, • Characterized— 1) abnormal fatigability of voluntary muscle on repetitive activity, and recover by rest. 2) electrophysiologically decremental response to repetitive stimulation by singlefiber electromyography. Myasthenia gravis 3) improve by administration of anticholinesterase drugs. 4) association with abnormality of thymus. 5) presence of circulating antibody to AChRs and complement-mediated damage to receptor. Clinical picture • Involvement of various voluntary muscle group. • Abnormal fatigability on repetitive activity with improvement after rest. • Progressive worsening symptoms through the day from morning to evening. • Ocular symptoms as diplopia and ptosis, • Weakness and fatigue transiently. Clinical picture • Bulbar innervated musculature is affected — dysphagia, dysarthria, difficult in mastication, failure of respiratory muscle. • Most serious symptoms are ventilatory failure. • In women — the symptoms may affected by pregnancy, menses and stress. Electrophysiology • Single fiber electromyography. • Record the jitter phenomenon. • Jitter is variable temporal separation of the response of individual muscle fibers of the same motor unit during activation. • Abnormally variable separation may found more than 80% patients with myasthenia gravis. Pharmacologic treatment • Loewi（1932）noted acetylcholine is neuromuscular transmission in cardiac muscle, Sir Henry Dale（1935）noted acetylcholine is liberated at motor nerve ending in voluntary striated muscle—1936 Nobel prize. • Propagation of action potential down a motor nerve fiber, release acetylcholine from synaptic vesicles, depolarization muscle. Pharmacologic treatment • Only a small fraction of the 30-40 million receptors per neuromuscular junction are activated normally in response to a nerve impulse. • The receptors excess provide large safety ensure the repetitively neuromuscular transmission. Pharmacologic treatment • Anticholinesterase—physostigmine, neostogmine, pyridostigmine— block the cholinesterase inactivation of acetylcholine, • Tensilon（edrophonium chloride） test— rapid action and rapid subsidence, a basic diagnostic test. Pathogenesis and immunobiology • Simpson (1960) — Autoimmune origin. • Almon (1974) — Demonstrate circulation antibodies to AChR site of neuromuscular junction. Pathogenesis and immunobiology • Three possible mechanism— 1)Accelerating the degradation of anticholinesterase receptor through the cross-linking phenomenon. 2)Direct blocking receptor site. 3)Actual degradation the receptor site by complement activation. Pathogenesis and immunobiology • Elevated antibody level are found in 90% patient and roughly correlated with clinical severity. • Immunosuppressive agents as azathioprine, corticosteroid, cyclosporine may have benefit effect. Pathology • Thymoma is present in 10-15% patient with myasthenia gravis. • Normal 10-25%. • Other is thymic hyperplasia. Thymectomy • Von Haberer 1917 — transcervical thymectomy because of thymic hyperplasia often found in thyrotoxicosis. • Blablock 1936— upper sternotomy incision and introduced neostigmine the operation is success. Thymectomy • Carlens (1968), Crile (1965), Akakura (1965) — re-describe the old technique of transcervical thymectomy. • Papatestas (1987) — perform more than 700 transcervical thymectomy. • Incomplete thymectomy is the most important problem. Thymectomy • Advantage of transcervical incision– incision only involve soft tissue, rarely enter the pleural space, well tolerated by patients. • Cooper (1988) —add self-retaining retractor to aid in transcervical exposure and able to extent transternal resection. • Type of surgical exposure is most important determinant of the extent of resection. Thymoma • 10-15% patient with MG has thymoma. • 30-50% thymoma are associated with MG. Classifications • • • • Modified Osserman and Genkin classification. Oosterhuis classification. Result classification. Immunobiological classification. Present indications for thymectomy • Patient with thymoma — the thymectomy is indicated all. • If no thymoma — the patient age, symptoms, duration, severity, response to medication, sex are factors in decision-making. Present indications for thymectomy • Thymectomy is not recommended for the neonatal type of myasthenia gravis. • In juvenile form — the reserve thymectomy for patient with more severe symptoms and lack of response to medical therapy. Present indications for thymectomy • In adult — Cooper, Jaretzki and Papatestas all believed patient with general symptoms should receive early thymectomy as soon as the diagnosis established. • The ocular type — may try medical therapy for a year and if the symptoms interfere the daily life, the thymectomy should be considered. • High incidence of unsuspected thymoma in patient older than 40y/o with ocular symptom only. Result • Adult patient without thymoma undergoing thymectomy has higher incidence of complete remission. • Complete remove all thymic tissue fom mediastium and lower neck from standard transternal incision is required in surgical treatment of myasthenia gravis.