• Neuromuscular junction : the synapse
between motor neuron and muscle fiber is called
the neuromuscular junction.
• Motor end plate contain nicotinic receptors, and
the Ach binds to these receptors leads to
the channels opens & permeability of motor end
plate to Na+ & K+ increases.
• Is an acquired autoimmune disorder.
• Is caused by autoantibodies that block the
function of postsynaptic Ach receptors at motor
• Some 60% of cases are associated with a peculiar
reactive hyperplasia of intrathymic B cells.
• And another 20% are associated with thymoma.
Myasthenia gravis can involve either the external
ocular muscle selectively (ocular MG)
or the general voluntary muscle system
(generalized MG) ,the symptoms usually
fluctuate tending to be worse later in the day
(diurnal fluctuation) .
they are worsened by exertion
• Ocular muscle involvement is usually bilateral
and asymmetrical and typically is associated
with ptosis and diplopia.
• Ocular muscles are affected in nearly all patients
after a year of disease.
• weakness of other muscles innervated by cranial
nerves result in loss of facial expression.
• Abnormal fatigability of the limb muscles
difficulty in combing the hair, lifting objects
repeatedly ,climbing stares, walking, and
• The symptoms are ocular in 40% ,
• And are generalized in 40%,
• involve only the extremities in 10%
• and involve only bulbar or bulbar and eye
muscles in another 10%.
• In about 10% the MG is associated with another
autoimmune disease, circulating Ach receptor
antibodies can be detected in most infants born
to myasthenic mothers, but only 12% of such
children develop transit neonatal MG,usually
during the first few hours of life.
• The disease is caused by transfer of Ach receptor
antibodies is self limited
Edrophonium given intravenously acts within a few
seconds and lasts for a few minutes. Two milligrams of
the drug are injected intravenously over 15 seconds. If no
response occurs in 30 to 45 seconds, an additional 8 mg
is injected. The evaluation of the response requires
objective assessment of one or more signs not easily
influenced by motivation, such as degree of ptosis and
range of ocular movements.
(tensilon test) cont.
Possible cholinergic side effects of the drug include
fasciculations, flushing, lacrimation, abdominal cramps,
nausea, vomiting, and diarrhea. The drug must be given
cautiously to patients with cardiac disease because it may
cause sinus bradycardia, atrioventricular block, and,
rarely, cardiac arrest. Atropine should be available
during the test. Edrophonium should not be given to
patients having respiratory difficulty.
Repetitive Nerve Stimulation
Supramaximal stimulation of a motor nerve at 2 or 3 Hz
results in a 10% or greater decrement of the amplitude of
the evoked compound muscle action potential from the
first to the fifth response. The test is positive in about
75% with generalized MG, provided that two or more
distal and two or more proximal muscles are examined.
It is less frequently abnormal (approximately 50%) in
purely ocular MG.
Single Fiber Electromyography
Single fiber electromyography (SFEMG) is currently the
most sensitive method for diagnosis of MG and reveals
increased jitter and blocking in 99% of patients with
generalized MG and in 97% of those with purely ocular
MG when a weak muscle is tested. SFEMG is usually
available only in specialized EMG laboratories
Blood Tests and Radiography
The AChR antibody test measures the binding of antibody
to AChR labeled with radioactive αbungarotoxin. The
antibody-binding test result is positive in nearly all adults
with moderately severe or severe MG, in 80% with mild
generalized MG, and in 50% with ocular MG. Some patients
without AChR have abnormal antibodies to MuSK, a
muscle-specific tyrosine kinase with a role in aggregation of
AChR and the end plate. Striated muscle antibodies also
occur in MG patients. Their role is unknown, but they are
often associated with thymoma. Because of the frequency of
thymomas, chest x-ray studies and chest computed
tomography (CT) scanning are indicated.
Pyridostigmine (60 mg tablet) is widely used. The duration of action
is 3–4 hours, the dose (usually 4–16 tablets daily) determined by
response. Pyridostigmine prolongs acetylcholine action by inhibiting
cholinesterase. Overdose of anticholinesterases causes severe
weakness (cholinergic crisis). Muscarinic side-effects, e.g. colic and
diarrhoea, are common; oral atropine (antimuscarinic) 0.5 mg helps
to reduce this. Anticholinesterases help weakness but do not alter
the natural history of myasthenia.
• These drugs are used in patients who do not
respond to pyridostigmine or who relapse on
treatment. Steroids are often used. There is
improvement in 70%, although this may be
preceded by an initial relapse. Azathioprine,
mycophenolate and other immunosuppressants
are also used.
• Plasmapheresis and intravenous
• During exacerbations these interventions are of
• Thymectomy improves prognosis, more so in
women than men below 50 years with positive
AchR antibodies, even in patients without a
thymoma. Cases positive for anti-MuSK
antibodies tend not to improve following
thymectomy. When a thymoma is present, the
potential for malignancy also makes surgery
• Andreoli and Carpenter s cecil essentials of
Medicine 8th edition
by: Thomas E. Andreoli, Ivor J. Benjamin, Ropert C. Griggs, Edward J.
•Robbins Basic Pathology 9th edition
Vinay Kumar, Abul K. Abbas, Jon C. Aster
• by Parveen Kumar and Michael Clark
• published by Elsevier