Management Of Myasthenia Gravis

Management Of Myasthenia Gravis- medicine cardiothoracic surgery

1. MANAGEMENT OF MYASTHENIA GRAVIS OKOYE, C CARDIOTHORACIC UNIT, DEPT OF SURGERY, ABUTH 24 /07/2020

2. OUTLINE Introduction Definition Epidemiology Pathophysiology Statement of Surgical Importance Classification Management History Examination Differential Diagnosis Investigations Treatment Prognosis Follow up Future Perspective Conclusion

3. Introduction The name myasthenia gravis ( MG ), which is L atin and G reek in origin means ‘grave’ or serious muscle weakness Available treatments can control symptoms and often allow people to have a relatively high quality of life. Most individuals with the condition have a normal life expectancy.

4. Introduction Thymectomy for myasthenia gravis, first used by Sauerbruchin 1912, was introduced again by Blalock in 1939 B ecame a widely used procedure in the last two decades, when large series of cases proved this treatment to be beneficial to patients with myasthenia .

5. Definitions Myasthenia gravis is a chronic autoimmune neuromuscular disease, that causes weakness in the skeletal muscles worsens by periods of activity and improves after periods of rest.

6. Definitions The thymus gland is a primary lymphoid organ that is involved in development and maturity of T-lymphocytes. It plays an important role in immunologic development in early life and begin to involute in adolescence. Thymic tumors are rare in children, most common in middle-aged adult.

7. Epidemiology MG affects 14 per 100,000 people in the United States and can affect any age group Of the 317patients studied in Poland, 252 were women F emale to male ratio being 3 . 9 :1. Forty one percent of patients were aged 20 - 30 years Men – peak incidence 50's to 60’s Thymic tumors found in 15% of patients

8. Epidemiology Of patients with MG, 75% have thymic disease, 85% have thymic hyperplasia, and 10–15% have thymoma

9. Statement of Surgical Importance The most common paraneoplastic syndrome associated with thymoma is myasthenia gravis (MG).  Findings from a recent NINDS-supported study yielded conclusive evidence about the benefits of surgery for even individuals without thymoma , a subject that had been debated for decades This presentation would attempt to highlight the association of thymoma with MG and associated clinical and therapeutic issues.

10. Osserman and Genkins Classification Pediatric myasthenia gravis A. Neonatal group (1%) Infants born of myasthenic mothers Self-limited, lasting no more than 6 weeks after birth Probably caused by tr B. Juvenile group (9%) Nonmyasthenic mother Onset any time from birth to puberty Tends to be permanent Familial involvement Myasthenia gravis disability classified as in adult myasthenia gravis

11. Osserman and Genkins Classification III. Adult myasthenia gravis Group 1: Ocular (15% to 20%) Limited to ocular muscles 40% ultimately develop clinically generalized disease Electromyographic results may be positive in peripheral muscles Group 2A: Mild generalized disease (30%) Involves cranial, limb, and truncal muscles Respiratory musculature spared Good response to anticholinesterase drugs Low mortality

12. Osserman and Genkins Classification Group 2B: Moderately severe generalized disease (20%) Significant diplopia and ptosis Bulbar muscle involvement: dysarthria, dysphagia, feeding difficulty Limb weakness Exercise intolerance

13. Osserman and Genkins Classification Group 3: Acute fulminating disease (11%) Abrupt onset Most severe symptoms appear by 6 months Early respiratory muscle involvement Severe bulbar, limb, and truncal weakness Poor response to anticholinesterases Frequent crises High mortality Thymoma relatively frequent

14. Osserman and Genkins Classification Group 4: Late severe disease (9%) Progression from milder disease after 2 years High incidence of thymoma Relatively poor prognosis

15. Classification based on muscle affected 1: Eye muscle weakness (EMW) 2: EMW and other mild muscle weakness Predominantly limb or axial muscles Predominantly bulbar or respiratory muscles 3: EMW and other moderate weakness Predominantly limb or axial muscles Predominantly bulbar or respiratory muscles 4: EMW and other severe weakness Predominantly limb or axial muscles Predominantly bulbar or respiratory muscles 5: Intubation needed to maintain airway

16. Management Resuscitation Sometimes the severe weakness of myasthenia gravis may cause respiratory failure, which requires immediate emergency medical care

17. Management History The onset of the disorder may be sudden, and symptoms often are not immediately recognized as myasthenia gravis . Painless   W eakness of the eye muscles (called ocular myasthenia) D rooping of one or both eyelids (ptosis) B lurred or double vision (diplopia)

18. Management History Changes in facial expression Difficulty chewing Difficulty swallowing Difficulty breathing Impaired speech (dysarthria) Weakness in the arms, hands, fingers, legs, and neck.

19. Management History Symptoms may worsen with exposure to extreme heat or emotional stress , infection , systemic illness, pregnancy, the menstrual cycle, or drugs that affect neuromuscular transmission Patients may report that they plan activities for early in the day when their strength is at its peak.

20. Management On Examination Do a general examination Findings may not be apparent unless muscle weakness is provoked by repetitive or sustained use of the muscles involved . Recognize a patient in whom respiratory failure is imminent.

21. Management On Examination Weakness of eyelid closure is seen in most patients with MG and should be specifically tested Patients are unable to whistle, suck through a straw, or blow up a balloon Sensory examination and deep tendon reflexes are normal.

22. Management On Examination Counting aloud (1 to 50): Enhances dysarthria (nasal, lingual, or labial) and results in dyspnea. Patient may sound relatively clear on speaking initially but will become increasingly dysarthric to the point of becoming unintelligible.

23. Myasthenic Crisis Requires immediate assistance Shortness of breath Extreme muscle weakness General fatigueablility Respiratory muscle paralysis Requires ventilatory supports

24. MG in Pregnancy Many mothers get worse 1st trimester and better 2nd and 3rd trimester. Up to 10% of infants born to mothers with MG will have Transient Neonatal Myasthenia. Weak cry, poor muscle tone, difficulty breathing etc…

25. Differential Diagnosis Lambert -Eaton Myasthenic Syndrome (LEMS) Multiple Sclerosis Brainstem Gliomas Chronic Myelogenous Leukemia (CML) Congenital Myasthenic Syndrome Dermatomyositis Diphtheria Graves Disease Guillain-Barre Syndrome

26. Differential Diagnosis Tolosa -Hunt Syndrome Thyroid Ophthalmopathy Myocardial Infarction Organophosphate Toxicity Polymyositis Pulmonary Embolism (PE) Tetrodotoxin Toxicity Amyotrophic Lateral Sclerosis Basilar Artery Thrombosis Botulism

27. Management Investigations; Electrodiagnostic studies (repetitive nerve stimulation and single-fiber electromyography ) Tensilon test CXR may identify an anterior mediastinal mass Chest CT to identify or rule out thymoma or thymic enlargement

28. Management Investigations In strictly ocular MG, MRI of the brain and orbit is helpful to evaluate for mass lesions compressing the cranial nerves or a brainstem lesion that may masquerade as ocular MG Blood tests Tests for specific antibodies TFT- RF- ANA

29. Management Treatment M ultidisciplinary and M ultimodal Medical and Surgical

30. Management Treatment decisions are based on predicted response to a specific form of therapy The treatment goals must be individualised according to severity of the disease, the patient’s age and sex, and the degree of functional impairment

31. Management Cholinesterase inhibitors Mestinon ( pyridostigmine bromide 30-60mg 6-8hrly Neostigmine 7.5-15mg 6-8hrly

32. Management Steroids Prednisolone 60-80mg/day Marked or complete relief of symptoms in 75% of patients

33. Management Immunosuppressants Azathioprine ( 2-3 mg/kg/ day ) Cyclosporine Mycophenolate mofetil Rituximab

34. Management Plasmapheresis and Intravenous Immunoglobulin ( IVIg ) Administered during myasthenic exacerbations to produce short-term clinical improvement Plasmapheresis rapidly lowers AChR antibody titers

35. Management Surgical Indications for surgery Patients with thymoma Patients aged 10-55 years without thymoma but who have generalized MG. A rapid increase of myasthenic symptoms Failure of medical management Advanced myasthenia with bulbar and respira - tory symptoms.

36. Management Surgical Thymectomy has been proposed as a first-line therapy in most patients with generalized myasthenia . Remission rate increases with time: at 7-10 years after surgery, it reaches 40-60% in all categories of patients except those with thymoma .

37. Management Surgical In the absence of a thymoma , 85% of patients experience improvement, and 35% of these patients achieve drug-free remission. In a study by Nieto et al, the rate of remission in the presence of thymic hyperplasia was 42% compared to 18% in patients with thymoma

38. Management Surgical Over the years, many different techniques have been employed to perform thymectomy . Although it is generally believed that complete removal of thymic tissue is better; this is not an established fact. There is no consensus as to whether one technique is superior to another in achieving benefit or minimizing risks. The Myasthenia Gravis Foundation of America (MGFA) has proposed a classification scheme for thymectomy , which is primarily based on techniques described in various published reports.  

39. Management Surgical The MGFA thymectomy classification is as follows: T-1 transcervical thymectomy – Basic; Extended T-2 videoscopic thymectomy – Classic VATS or VATET T-3 transsternal thymectomy – Standard; Extended T -4 transcervical and transsternal thymectomy

40. Prognosis Disease course is highly variable; ranging from remission to death . Ocular Myasthenia has the best prognosis . Thymectomy results in complete remission of the disease in a number of patients. Mortality rate is 2-3%

41. Follow Up Educate patients about the fluctuating nature of weakness and exercise-induced fatigability. Follow-up by specialists is necessary to secure optimal treatment regarding effect on muscle strength, as well as to avoid unnecessary side effects . Rehabilitation

42. Future Perspective Until an antigen-specific MG treatment is available, it remains a challenge to evaluate new and promising immunoactive drugs for MG. The aim should be to suppress the anti- AChR , anti- MuSK immune response in MG patients without influencing the rest of the immune system

43. Conclusion The management of MG involves a multidisciplinary and multimodal approach F rom establishing diagnosis, deciding the therapeutic strategy and evaluating the prognosis. With advances in medical science, new surgical techniques and drugs, there is a remarkable improvement in the management of MG.  

44. THANK YOU

45. References Blalock A. Thymectomy in the treatment of myasthenia gravis. J Thorac Surg 1944;13:316-39. Schumacher CH, Roth P. Thymektomie bei einem Fall von Morbus Basedowi mit Myasthenie . Mitt Grenzgeb Med Chir 1912;25:746-65. Keyness GL. The results of thymectomy in myasthenia gravis. Br Med J 1949;ii:611-6. 4 Keyness GL. Surgery of the thymus gland. Lancet 1954;ii: 1197-208. Evoli A, Tonali PA, Padua L, Lo Monaco M, Scuderi F, Batocchi AP, Marino M, Bartoccioni E. Clinical correlates with anti- MuSK antibodies in generalized seronegative myasthenia gravis. Brain. 2003;126:2304–2311. doi : 10.1093/brain/awg223.  Hoch W, McConville J, Helms S, Newsom-Davis J, Melms A, Vincent A. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med. 2001;7:365–368. doi : 10.1038/85520. Jaretzki A, III, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, Sanders DB. Myasthenia gravis: Recommendations for clinical research standards. Neurology. 2000;55:16–23.