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