Myasthenia gravis is a neuromuscular disorder characterized by weakness and fatigue of muscles due to autoantibodies against acetylcholine receptors, resulting in a decreased number of receptors. It is caused by antibodies that decrease available acetylcholine receptors by damaging postsynaptic membranes, blocking receptor sites, or accelerating receptor turnover. Treatment involves anticholinesterases, immunosuppressants, thymectomy, plasmapheresis, and IVIg. Disease severity is classified using the Osserman classification system.

1. MYASTHENIA GRAVIS

2. DEFINITION OF MG
• NEUROMUSCULAR DISORDER
CHARACTERISED BY WEAKNESS AND FATIGUE
OF MUSCLES
• DUE TO AUTOANTIBODY AGAINST AchR
• DECREASED NO. OF AchR

3. pathology

4. Normal physiology
• Whenever the presynaptic neuron is
stimulated, it releases the stored “Ach” from
the vesicle to act on the AchR on the post
synaptic membrane which is comprising of
five subunits (2 alpha, 1 beta , 1 delta, 1
gamma/ 1 epsilon)

5. NORMAL PHYSIOLOGY
• Once the Ach reaches the AchR it acts on this
receptor and forms the pore, to allow the ions
mostly Na+ and depolarisation takes place and
hence muscle contraction

6. Pathology in MG
• FEMALES OUTNUMBER MALES (3:2)
• AND THE AGE OF ONSET IS IMPORTANT FOR
DIFFERENTIAL
• FEMALES – SECOND DECADE
• MALES – THIRD DECADE

7. • IF THERE IS CASE SUGGESTIVE OF WEAKNESS OF
EYE (I.E DIPLOPIA, PTOSIS ) IN YOUNG AGE
SHOULD SUSPECT THE CONGENITAL MYASTHENIC
SYNDROME.
• OTHER D/D
LEMS (LAMERT-EATON MS)
HYPERTHYROIDISM
PENICILLAMINE THERAPY FOR RA
NEURASTHENIA

8. • IN MG, THERE IS DECREASE IN THE NO. OF
AchR and flattening of synaptic folds(look in
the previous picture),
• These changes decrease the efficiency of
transmission of Ach , result in inefficient
action potential, so the watchman(AchR)
don’t open the gates to Na+(or small way), so
less action potential

9. • The amount of Ach released per impulse
decreases gradually called “PRESYNAPTIC
RUNDOWN”

10. ANTIBODIES IN MG
• ANTI-AchR decreases the available AchR by
three mechanism
– Damage to post – synaptic membrane
incombination with complement
– Blockade of active site of AchR
– Accelerated turnover of AchR by mechaism
involving cross linking and rapid endocytosis of
receptor

11. Antibodies in myasthenia gravis
• They are IgG and T – cell dependent
• Musk- muscle specific kinase
• Anti AchR
• Anti – lrp4(lipoprotein related protein 4)
• And recently agrin(from the motor nerves )

12. Thymus and MG
• THYMUS PLAY AN IMPORTANT ROLE
• PATHOGENESIS IN MG IS SUGGESTED BY THE
PRESENCE OF MUSCLE LIKE CELLS IN MG- WHICH
WILL PRODUCE AUTO-IMMUNE RESPONSE.
• MOST COMMON LESION
• THYMIC HYPERPLASIA> THYMOMA

13. CLINICAL FEATURE
• IT CAN BE EITHER RESTRICTED TO OCULAR MG OR
GENERALISED
• THERE SHOULD NOT BE ANY SENSORY OR AUTONOMIC
DISTURBANCES (IN LEMS +)
• IN CASE, IF A PATIENT REPORTED ONLY WITH
DROPPING OF EYELIDS AND DIPLOPIA AND IT WAS THE
ONLY COMPLAINT HAD FOR MORE THAN 3 YEARS
OCULAR MG

14. • MUSCLE WEAKNESS IN CHARACTERISTIC PATTERN
• -PTOSIS
• DIPLOPIA
• SMILING PRODUCES SNARLING EXPRESSION
• ANTI-MUSK POSITIVE – HAVE BULBAR WEAKNESS

15. ANTIBODY
• ANTI-AchR does not correlate with severity of
disease
• But increased level  exacerbation
• And decreased level on treatment , implies
the treatment is working

16. Electrodiagnostic testing
• On successive impulses, there is a drop of
amplitude by 10-15 % suggestive of MG
• DECREMENTAL RESPONSE – MG AND OTHER
DISORDERS
• INCREMENTAL RESPONSE - LEMS

17. ANTI-CHOLINESTERASE TEST
• TENSILON TEST
• IV.EDROPHONIUM 2MG  IMPROVEMENT IN
MUSCLE STRENGTH  POSITIVE
• IF NEGATIVE  8MG EDROPHONIUM IN TWO
DOSES( ATROPINE IN HAND TO COUNTER THE
S/E)

18. TENSILON TEST
• THIS TEST IS NOW RESTRICTED TO THE
PATIENTS
• WHO ARE
– ANTIBODY NEGATIVE
– INCONCLUSIVE ELECTRODIAGNOSTIC TESTING

19. INHERITED MYASTHENIC SYNDROMES
• 4 TYPES
• SLOW CHANNEL TYPE
• A.D
• MUTATION IN RECEPTOR IN AchR
• M/C PRESENTATION – WEAK FOREARM
EXTENSOR
• ANTI-ACHE DANGEROUS

20. INHERITED MYASTHENIC SYNDROMES
• LOW – AFFINITY FAST CHANNEL
ONSET EARLY
AR
BRIEF AND INFREQUENT CHANNEL OPENING
NORMAL END PLATE STRUCTURE
RESPOND TO 3,4 DAP AND ANTI ACHE

21. SEVERE AchR
• A.R
• EPSILON SUBUNIT OF ACHR MORE COMMON
• DECREMENTAL RESPONSE TO
ELECTRODIAGNOSTIC STUDY

22. ACHE DEFICIENCY
EARLY ONSET
WORSE WITH ANTI-ACHE
TREATMENT BY ALBUTEROL, EPHEDRINE

23. MANAGEMENT
• ANTICHOLINESTERASE
– PYRIDOSTIGMINE 30-60MG THREE TO FOUR
TIMES DAILY
– ANTI-MUSK POSITIVE INDIVIDUALS WONT SHOW
PROMISING RESPONSE

24. • THYMECTOMY
– ANTI-MUSK RESPONSE LESS THAN ANTI-ACHR

25. • IMMUNOSUPPRESSANTS
• GOOD RESPONSE IN ALL MG PATIENTS

26. IMMEDIATE IMPROVEMENT
• PLASMAPHERESIS
• IVIg

27. INTERMEDIATE
• GLUCOCORTICOIDS
• CYCLOSPORINE/TACROLIMUS

28. LONG TERM
• AZATHIOPRINE(DON’T USE ALLOPURINOL
CONCURRENTLY)
• MYCOPHENOLATE MOFETIL(SAFEST)- fewer
GIT s/e

29. • RITUXIMAB – PARTICULARLY EFFECTIVE FOR
ANTI - MUSK

30. MEDICALLY REFRACTORY MG
• IN LAST – CYCLOPHOSPHAMIDE (IT ACTUALLY
REBOOTS THE IMMUNE SYSTEM)

31. OSSERMANN CLASSIFICATION
• CLASS I – ANY OCULAR MUSCLE WEAKNESS
• CLASS II MILD WEAKNESS OTHER THAN
OCULAR
• CLASS II A – PREDOMINANTLY LIMB, AXIAL OR
BOTH
• CLASS IIB – PREDOMINANTLY
OROPHARYNGEAL

32. OSSERMAN CLASSIFICATION
• CLASS III – MODERATE WEAKNESS OTHER
THAN OCULAR
• III A – PREDOMINATLY LIMB OR AXIAL OR
BOTH
• III B – PREDOMINALTY RESPIRATORY OR
OROPHARYNGEAL

33. OSSERMANN CLASSIFICATION
• CLASS IV : SEVERE WEAKNESS OTHER THAN
OCULAR
• IVA – PREDOMINANTLY LIMB OR AXIAL OR BOTH
• IV B – PREDOMIANTLY RESPIRATORY OR
OCULOPHARYNGEAL
• CLASS V : INTUBATION WITH OR WITHOUT
VENTILATION

34. MYASTHENIC CRISIS(MAY BELONGS TO
CLASS V)
• IF THE MG PATIENTS IS ON RESPIRATORY
SUPPORT
• M/C/C – INFECTIONS
– TREATMENT FOR INFECTION SHOULD BE
AGGRESSIVE

35. MYASTHENIC CRISIS
• MUST RULE OUT THE EXCESSIVE USE OF ANTI-
ACHE BY TEMPORARILY STOPPING THE DRUG

36. DRUGS SHOULD BE AVOIDED IN MG
• MNEMONIC – AB MP
• A-ANASTHETICS
– LOCAL ANAESTHETICS
• PROCAINE,XYLOCAINE IN LARGE AMOUNTS
NON-DEPOLARISING MUSCLE RELAXANTS

37. • ANTIBIOTICS
– AMINOGLYCOSIDES
– QUINOLONE
– MACROLIDES
– QUININE DERIVATIVES (USEFUL IN SLOW
CHANNEL MG)

38. • B – BOTULISM TOXIN
– BETA BLOCKING AGENTS(PROPANOLOL)

39. • M – MAGNESIUM
• DECREASE THE RELEASE OF Ach from the
nerve
• P- PENICILLAMINE
• CAUSE AUTOIMMUNE MG