Myasthenia gravis guest_lecture[1]

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Myasthenia gravis guest_lecture[1]

  1. 1. HARVARD MEDICAL SCHOOL DEPARTMENT OF NEUROLOGY MASSACHUSETTS GENERAL HOSPITAL Myasthenia Gravis Shirley H. Wray, M.D., Ph.D.Professor of Neurology, Harvard Medical School Director, Unit for Neurovisual Disorders Massachusetts General Hospital
  2. 2. HistoryA detailed history often reveals evidence of early, unrecognized myasthenic features: Intermittent diplopia Frequent purchases of new glasses to correct blurry vision, difficulty focusing and/or early onset of convergence insufficnecy of a need for prism correction Use of dark glasses to reduce diplopia or hide drooping eyelids
  3. 3. History continued.Avoidance of certain foods that becomedifficult to chew and swallowCessation of activities that requireprolonged use of muscle activity
  4. 4. Myasthenia Gravis Clinical ClassificationI. Ocular aloneIIa. Mild generalizedIIb. Moderately severe generalized plus usually some bulbar involvementIV. Acute severe over weeks-months with severe bulbar involvementV. Late severe with marked bulbar involvement
  5. 5. Ocular Myasthenia GravisBecause the majority of patients withmyasthenia gravis present with ocularmanifestations, the ophthalmologist playsan essential role in the diagnosis of thiscondition and a high index of suspicionfacilitates the diagnosis
  6. 6. Muscle groups involved at onset Analysis of 295 casesOcular alone 34%Bulbar alone 8%Extremities alone 15%Ocular and bulbar 7%
  7. 7. Muscle group analysis continued. Ocular and extremities 7% Bulbar and extremities 6% Ocular, bulbar and extremities 21%Simpson et al, Acta Neurol. Scand. 1966 suppl. 23 pl
  8. 8. Extraocular Muscles Analysis of 295 cases NumberUnilateral ptosis 37Bilateral ptosis 36Unilateral EOM paresis 8Bilateral EOM paresis 32
  9. 9. Extraocular muscles continuedBilateral ptosis and EOM paresis 57Unilateral ptosis and EOM paresis 16Unilateral ptosis and bilateral paresis 13 Simpson et al, Acta Neurol. Scand. 1966 suppl. 23 pl
  10. 10. Eyelids The findings on examination of the lids may simulate:Congenital ptosisSenile ptosisHorner’s syndromeLevator dehiscenceSuperior division 3rd nerve palsyNuclear 3rd nerve palsyMitochondrial myopathy
  11. 11. PtosisUnilateral (partial or complete), alternatingwith or without paradoxical lid retraction,or see-saw ptosisBilateral and asymmetric, variable inseverityLid twitch – Cogan signVariable levator function
  12. 12. Ptosis continued.Weakness of the orbicularis oculiIncreased ptosis with repetitive eyeclosureRecovery of ptosis with gentle eye closure
  13. 13. To Document PtosisMeasure the palpebral fissure beforetesting EOM, giving Tensilon, or usingsympathomimetic drugsIncrease of ptosis on fatigueMyasthenic lid twitchRecovery of ptosis following gentle eyeclosure
  14. 14. To document ptosis continued.Range of levator function+ Weakness orbicularis oculiPhotograph and compare with familysnapshotsMeasure response to IV Tensilon
  15. 15. PtosisMyopathy MyastheniaSymmetric Appearance AsymmetricNo Ptosis on fatigue YesNo Lid twitch YesNo Recovery w/ eye closure YesConstant Range lev. function VariesYes Weak orb. oculi YesNegative Tensilon test Positive50% Family history RareSlowly Progressive Course Fluctuates
  16. 16. Saccades Examination may show:Intrasaccadic fatigue (slow in midflight)Decrescendo from saccade to saccadeHypermetria of small saccadesHypometria of large saccadesQuiver movements and “hyperfast”saccadesFatigability of quick phases on OKN
  17. 17. Myasthenia GravisMyasthenia gravis is a disease of skeletalmuscle acetylcholine receptors. Thechemical transmitter, acetylcholine (ACh) isunable to bind to the receptors (AChR) onthe postsynaptic membrane to transmit thenerve impulse to muscle fibers to produce amuscle contraction
  18. 18. Presentation (I)MG occurs at any age, involves eithersex and begins insidiouslySecond and third decades commonestage of onset in women. Seventh andeighth decades in menPatients complain of specific muscleweakness, not generalized fatigue
  19. 19. Presentation (II)Ptosis or diplopia – initial symptoms in65% of patientsOropharyngeal muscle weakness –difficulty in swallowing and talkinginitial symptoms in 17% of patientsLimb weakness presenting symptom inonly 10% of cases
  20. 20. Presentation (III)Characteristically, severity of weaknessfluctuates during the day, least in themorning, worsening as the dayprogresses, especially after prolonged useof affected musclesIn the era before corticosteroid treatment,approximately one-third of patientsimproved spontaneously, one thirdbecame worse and one third died
  21. 21. Presentation (IV)Ocular myasthenia – if progressing togeneralized MG usually does so within thefirst two years after onsetAfter 15 to 20 years, weakness becomesfixed. The Burnt-Out-Stage + muscleatrophy
  22. 22. Edrophonium Chloride Tensilon Test (10 Mg in 1 cc)Precautionary Steps:List all medications being takenHistory of drug allergy and previousreaction to TensilonPerform the test in the ER with an ambubag, atropine and adrenalin available inelderly patients and those with cardiacdisease
  23. 23. Administration ProcedureThe ideal dose of Tensilon cannot bepredeterminedGive a 0.1 cc test dose and monitor pulse,blood pressure and clinical stateFollow with 0.3 cc aliquotes examining fora response in ptosis, EOM or Lancasterstrabismus screen test after each oneOnce improvement is seen -- STOP
  24. 24. The defect in neuromusculartransmission in MyastheniaGravis is due to: The muscle end-plate membrane is distorted Acetylcholine receptors are lost from the tips of the folds, and antibodies attach to the postsynaptic membrane Ach is released normally but absence of receptors prevents the transmitter binding to the muscle membrane
  25. 25. Acetylcholine Receptor Antibodies75% of cases generalized MG have serumantibodies (Ab) that bind to huma AChR54% with ocular MG have antibodies 10%MG cases with no binding antibodies haveother antibodiesThe AChR Ab tit varies widely amongpatients with similar degrees of weakness.The amount of Ab in the serum does notpredict the severity of the disease inindividual patients
  26. 26. Antibodies continued.The Ab level may be low at onset on MGand gradually become elevated in latestageWorthwhile to repeat test when initialvalues normal
  27. 27. The Presence of AChR Antibodyis not diagnostic for MG, alsopresent in: Systemic lupus erythematosus Inflammatory neuropathy Amyotrophic lateral sclerosis Rheumatoid arthritis in patients taking D- penicillamine In cases of thymoma without MG
  28. 28. Association of MG with other diseasesHyperthyroidism 6%Rheumatoid arthritis, less than2%Systemic lupus erythematosus 2%Diabetes mellitus 7%Non thymus neoplasm 3%
  29. 29. Differential DiagnosisGraves ophthalmopathyProgressive External Ophthalmoplegia(PEO)Oculopharyngeal DystrophyMyotonic DystrophyThe Lambert-Eaton Myasthenic Syndrome(LEMS)Guillian Barre Syndrome – Miller Fishervariant
  30. 30. Factors that Aggravate MGEmotional stressSystemic illness e.g. viral URIThyroid disease, hyper or hypoPregnancyMenstrual CycleIncrease in body temperatureDrugs
  31. 31. TreatmentTreatment decisions are based on thepredicted response to a specific form oftherapyTreatment goals must be individualizedaccording to the severity of the disease,the patient’s age and sex, and the degreeof functional impairment
  32. 32. Treatment continued.The response to any form of treatment isdifficult to access because the severity ofsymptoms fluctuates. Spontaneousimprovement, even remissions, occurwithout specific therapy, especially duringthe early stages of the disease
  33. 33. CHE Inhibitors (I)Mestinon (Pyridostigmine bromide) firstchoice, dose 30-60 mg q 6-8 h/dailyProstigmine (Neostigmine bromide) 7.5 –15.0 mg q 6-8 h/dailyNo fixed dosage schedle suits all aptients
  34. 34. CHE Inhibitors (II)The need for ChE inhibitors varies fromday to day and during the same dayDifferent muscles respond differently withany dose, certain muscles get stronger,others do not change and still othersbecome weakerThe drug schedule should be titratedaccording to the pateints work load andmuscle activity
  35. 35. ChE Inhibitors (III)Many patients assume responsibility fortheir own drug doseThe goal is to keep the dose low enoughto provide definite improvement 30 to 40minutes later and allow theeffect to wearoff before the next doseAdvise patients re: adverse effects of ChEinhibitors
  36. 36. PrednisoneMarked improvement or complete relief ofsymptoms occurs in 75% of casesImprovement in first 6 to 8 weeks, butstrength may increase to total remissionover monthsBest responses in patients with recentonset MG, but chronic disease may alsorespond
  37. 37. Prednisone continued.The severity of the disease does notpredict the ultimate improvementPatients with thymoma have an excellentresponse to prednisone before or afterthymectomy
  38. 38. DosePrednisone 60 to 80 mg/day given untilsustained improvement (usually 2 weeks)then alternate days beginning with100-120 mg tapered over months tolowest dose necessary (usually less than20 mg alternate days)
  39. 39. http://www.library.med.utah.edu/NOVEL

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