MYASTHENIA GRAVIS

1. MYASTHENIA GRAVIS GENERAL THORACIC SURGERY CHAPTER 168

2. 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 single-fiber electromyography.

3. 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.

4. 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.

5. 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.

7. 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.

8. 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.

10. 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.

11. 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.

12. Pathogenesis and immunobiology • Simpson (1960) — Autoimmune origin. • Almon (1974) — Demonstrate circulation antibodies to AChR site of neuromuscular junction.

13. 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.

14. 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.

15. Pathology • Thymoma is present in 10-15% patient with myasthenia gravis. • Normal 10-25%. • Other is thymic hyperplasia.

16. 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.

17. 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.

18. 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.

19. Thymoma • 10-15% patient with MG has thymoma. • 30-50% thymoma are associated with MG.

20. Classifications • Modified Osserman and Genkin classification. • Oosterhuis classification. • Result classification. • Immunobiological classification.

24. 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.

25. 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.

26. 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.

27. 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.