05 November 2004
autoimmune disorder characterised by abnormal muscle fatiguability due to
nicotinic acetylcholine receptor antibodies
in motor end plates of striated muscle.
20 – 30 in women
50 – 60 in men (tend to be associated with thymomas)
by certain drugs especially penicillamine
mild generalised myasthenia with slow progression, no crises, drug
moderately severe generalised myasthenia, severe skeletal & bulbar
involvement but no crises; less than satisfactory drug response
acute fulminating myasthenia, rapid progression of severe symptoms with
respiratory crises & poor drug response; high incidence thymoma; high
late severe myasthenia, same as III but progression over 2 yrs from class
I to II
myasthenia gravis with thymoma, no sex nor HLA association, high antibody
onset < 40 yo, no thymoma, female predominant,
HLA A1, B8, DRW3 associations.
Onset > 40 yo, no thymoma, male predominant, low antibody titre, HLA
A3, B7, DRW2 associations.
% initial manifestation is ocular symptoms (ptosis, palsy, pseudoINO)
will eventually develop ocular symptoms at some stage
will eventually develop some form of faciobulbar palsy
flexion (parallels bulbar & respiratory function)
upward eye gaze, trident tongue, ice eye test, Cogan’s lid twitch sign.
lymphofollicular hyperplasia in thymus
connective tissue disease
FHx of autoimmune disorder
Ach Receptor antibody: 80% with generalised myasthenia, 60% ocular
myasthenia. Associated with blocking of Ach binding, degradation of Ach
receptors, destruction of postsynaptic folds.
Repetitive nerve stimulation +/- Tensilon (75-80% sensitive):
decrementing CMAP >10% at 3 Hertz in distal ulnar/median, accessory, facial;
exercise for 1 min followed by RNS at 0 sec, 30 sec, 1, 2 & 3 min.
Single fibre EMG: 92 % sensitive
Antistriated muscle antibody (thymoma association): titin, myosin, actin,
Ryanodine receptor antibody (thymoma association)
Antibody negative maybe due to failure of assay, antibody strongly bound
to antigen, antibody binding to voltage gated sodium channels, other end plate
9. Ice pack test: apply ice pack to eye with ptosis for 2 minutes to see whether ptosis resolves or improves. (This is essentially a reverse Uhthoff's phenomenon in the peripheral nervous system).
Septic workup and check medications
Tensilon test exclude cholinergic crisis
Repeat repetitive nerve stimulation / EMG: steroid myopathy vs myasthenia
CT chest for residual thymus tissue
Thymectomy recommended virtually for all patients from puberty to 60 yo
especially so for thymoma and myasthenics with poor drug response. In case of
thymoma, radiation for residual tissue & platinum based chemo for
invasion/spread. Achieves 35 % remission rate & 50% will improve. Best
response after 3 yrs.
Prednisolone 1 – 1.5 mg/kg/day initially. 75% patients will improve.
Eventually reduce to alternate day regimen. May initially exacerbate myasthenia.
Azathioprine (Myasthenia Gravis Clinical Study Group): steroid sparing
agent or who fail to respond to steroids. Slow onset of action from 3 –12 mths.
Combination of pred & aza better than either drug alone in severe disease,
achieves longer remission. Main SE
is mutagenicity, monitor LFT & wcc.
Cyclophosphamide rarely used due to toxic profile.
Cyclosporine with improvement in 1 –2 mths.
Intragam 0.4 mg/kg/d for 5 days (NB based on studies for ITP &
Kawasaki’s disease). Occasionally used long term as monthly infusions.
Plasma exchange for myasthenic crisis as fastest acting at 250 ml/kg for
at least 5 exchanges. Occasionally used long term.
Total body irradiation
patients have one episode of myasthenic crisis usually within first 2 yrs.
flexion & oropharyngeal weakness marker impending crisis.
set pattern except 30% will have postpartum exacerbation.
of myasthenia in babies.