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‡ Most common disorder of neuromuscular transmission
‡ Hallmark of disorder-- fluctuating degree & variable combination of
weakness in occular, limb, bulbar, respiratory muscle
‡ Mechanism-
± Antibody mediated , T cell dependent immunological attack directed at
protein in post synaptic membrane of neuromuscular junction (A/Ch
receptor &/or receptor associated protein)
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‡ 2 clinical forms- Occular & Generalized
‡ Occular MG-
± Weakness is limited to eyelids & extra occular muscles
‡ Generalized MG-
± Commonly affect occular muscles
± Also involves variable combination of limb, bulbar, respiratory muscles

‡ Pt who have detectable antibodies to AChR are called as

SERO-POSITIVE MG, & those without are called as SERO-
NEGATIVE MG

‡ 10-15% of pt have underlying thymoma

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‡ Occurs at any age; Bimodal distribution-
± Early peak in 2nd & 3rd decades ( female predominant)
± Late peak in 6th & 8th decades ( male predominant)
±
‡ Cardinal feature - fluctuating skeletal muscle
weakness, often with true muscle fatigue
± Fatigue- is manifested by worsening contractile force of
muscle ,not a sensation of tiredness
± Weakness- fluctuate through out day, more worse in
evening or after exercise
 
‡ OCCULAR MUSCLE: Ptosis; Diplopia
‡ BULBUR MUSCLE: fatiguable chewing; dysarthria, dysphagia;
speech sounds nasal, nasal regurgitation
‡ FASCIAL MUSCLE- Expressionless face, ³lost smile´
‡ NECK MUSCLE-Flexor & extensor are commonly affected
‡ LIMB MUSCLE- Predominantly proximal muscle; Arm > leg
‡ RESPIRATORY MUSCLE-
± Respiratory distress± respiratory falure± ³Myesthenia crisis´
± Spontaneously during active phase of disease OR
± PPT by- surgery, infection,certain medication, tappering
immunosuppresion
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‡ Early in disorder ,symptoms -- transient with hrs, days, wks, free of symptoms
‡ Maximal extent of disease -- by 3 yrs of onset
‡ 3 phase-
‡ 1st phase-
± Active phase--most fluctuation & most severe symptoms -in 5 to 7 yr of
onset
± Mysthenia crisis occur during this phase
‡ 2nd phase-
± Symptoms are stable ,but persistant
± Worsen on infection, medication taper,surgery
‡ 3rd phase-
± Remission may occur
± Free of symptoms on immunotherapy or off medication
     
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‡ EDROPONIUM CHLORIDE (tensilon) ±
± Acetylcholinesterase inhibitor, with rapid onset (30-45 sec)& short duration (5-10
min)
± Results in increase in muscle strength of affected pt
‡ Initial 2 mg IV of test dose--followed by 2 mg IV every 60 sec.--up to total 10 mg
‡ Most pt responded by 4 to 6 mg

‡ Advantage of incremental dose-

± Avoid excessive muscarinic effect
± In some pt ,occular muscle strength improves at lower dose, paradoxical response
at higher dose

‡ Adverse effect-
± Bronchospasm, GI cramp, bradycardia
‡ Sensitivity- 80-90 %
‡ Many false positive &false negative
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‡ 3 Ach R-Ab assay- binding ,blocking, modulating
‡ Binding Ab are most sensitive
‡ Measured by Radioimmuno assay
‡ Highly specific for MG (90%)
‡ 85 % sensitive
‡ In seronegative MG - can test MuSK antibodies (muscle
specific tyrosine kinase)
± Antibodies to MuSK are present in 40-50 % pt with seronegative MG
  
    
‡ REPETITIVE NERVE STIMULATION:
± Performed by putting recording electrodes over end plate region of
muscle, & stimulating motor nerve of that muscle
± Compound muscle action potential (CMAP) is noted
± In normal person- no change in CMAP on repetitive stimulation
± In MG- progressive decline in CMAP amplitude ( >10 %
decrement)
± Sensitivity ± 75 %

‡ SINGLE FIBER ELECTRO MYOGRAPHY:

± More technically demanding ;less widely available
± Most sensitive-95%
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‡ MRI BRAIN/CT ORBIT:
± To r/o other neurological problem
± To differentiate from thyroid opthalmopathy

‡ THYROID FUNCTION TEST

‡ RHEUMATOID FACTOR
‡ ANTI NUCLEAR ANTIBODY:
± to r/o other autoimmune disorder

‡ CT SCAN CHEST-
± To look for thymoma
  
4 basic therapies—
1. Symptomatic Rx (anticholinesterase)
2.Chronic immunomodulating agent (corticosteroids &
other immunosuppresive agent)
3.Rapid immunomodulating Rx ( IVIG, plasma
exchange)
4.Surgical Rx (thymectomy
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‡ Anti cholinesterase- retard breakdown of A/Ch at NMJ, effect of A/Ch is
prolonged, variable improvement in muscle strength
‡ Limb & bulbar muscle respond better than occular muscle
‡ Only for symptomatic therapy ,not sufficient in generalized myesthenia

‡ Rapid onset (15-20 min), peak at 2 hr, last for 3-4 hr

‡ Started with 30 mg TID--- up to 120 mg Q 3-4 hrly

‡ Cholinergic side effects-

± Diarrhea, increase secretions, abdominal cramp--controlled by ±
glycopyrrolate
‡ CHOLINERGIC CRISIS:
± Excessive anticholinesterase ± weakness
± Rarely seen if dose is limit up to 120 mg Q3H
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‡ CORTICOSTEROIDS:
± Moderate to high dose ± complete remission in 30 % pt,
marked improvement in 50% pt
± Onset of benefit ±begins with 2-3 wks
± Transient deterioration ± in 50% pt, with high dose of
corticosteroids«.5-10 days after initiation, lasting around 5-
6 days
± So, high dose in only hospitalized pt ( intubated) who are
receiving plasma exchange or IVIG
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‡ As steroid sparing agent
‡ Started early to facilitate weaning from steroids
‡ Takes month for effect

‡ MYCOPHENOLATE- becoming agent of choice, better

tolerated, faster onset than azathioprim
‡ Cyclosporine, Azathioprim --can be used

‡ Monitoring of COUNTS & LFT is required

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‡ Regimens -- same as for GBS
‡ Indications -
a) Severe symptoms
b) As a bridge for steroids/ other agents
c) Pre-operatively prior to Thymectomy
d) In chronic myasthenia unresponsive to maintenance regimens

‡ Both take effect within 3-5 days and last 3-5 weeks only

‡ Plasma exchange in one small study was found to reduce

need for MV & improve 1 month outcomes compared to IVIG
 

‡ Thymoma mandates thymectomy --once patient completely
stabilised and is an outpatient
± Needs to have disease very well controlled and be on relatively small doses of
steroids prior to surgery
± Treated pre-operatively with IVIG or Plasmapheresis to facilitate post-op
extubation and pulmonary status

‡ Patients without thymoma-

± Can benefit from thymectomy---especially younger patients (<60 years)
± Who undergo thymectomy--1.5-2 times more likely to be remission free/ off
medicines/ asymptomatic than those who are not operated

‡ Open thoracotomy -preferred approach

‡ Minimally invasive approaches -- higher risk of recurrence

‡ Benefit of thymectomy takes several years