The symptoms of Myasthenia Gravis (MG) are common
complaints that can be found in a variety of medical and even
psychological conditions. The symptoms include drooping eyelids,
double vision, difficulty chewing or swallowing, weakness in
almost in any part of the body, and even simple fatigue. One
can see that the symptoms of MG are not specific to the condition.
This can make it difficult to diagnose MG, particularly in cases
where the condition is mild, or where the doctor is not familiar
enough with MG to suspect the condition. Generally an individual
with potential symptoms of MG would be referred to a neurologist
for diagnosis, but sometimes an ophthalmologist or an immunologist
will also make the diagnosis.
There are many different kinds of disorders that
can cause symptoms similar to MG, and so a complete history
and both general and neurological examination are important
first steps in diagnosing MG and ruling out other disorders.
This may include a careful family history, past medical history
and medication history; as the disorders that can mimic MG can
occur for many different reasons. It may therefore be important
that your doctor has access to your previous medical records
and any previous tests, in particular this includes scans and
x-rays. This section does not address the tests that might be
required to investigate potential diagnoses other than MG.
It is not often realised that there is no single
test that absolutely proves the diagnosis of MG. However, the
combination of history, clinical examination, nerve tests and
blood tests often establishes the diagnosis beyond reasonable
doubt. If there is doubt after the tests have been completed
often a trial of treatment for MG helps clarify the issue, and
the diagnosis also often becomes clearer in the longer term.
The doctor should know as much as possible about all symptoms
that the patient is experiencing. The patient should be quite
specific about what symptoms are occurring, the time of day,
the circumstances, what brings it on or makes it better, and
what is actually felt. If specific muscles are more affected
let the doctor know. If the doctor suspects MG, further tests
are usually carried out.
There are certain symptoms that are more suggestive of MG. These
· double vision or drooping of the eyelids that comes
and goes, particularly if it is worse towards the end of the
· speech becoming weak or nasal after a few minutes of
· difficulty with chewing or swallowing that gets worse
after a few minutes or with something difficult to chew, such
· the head suddenly dropping forwards without the patient
· weakness in the shoulders or hips that gets worse towards
the end of the day
A neurological exam can involve many things, but if MG is suspected
it will be focused on the findings that may occur in MG.. The
doctor may also look for the findings that may indicate an alternative
diagnosis. An examination focused on MG will test various general
areas: the eyes, speech and swallowing, the neck, and the arms
and legs, plus other things as determined by the circumstances.
The concept of fatigability is particularly important for MG,
and this is when the muscle is initially strong but after some
seconds becomes weaker.
· In the eyes the doctor might check the eyelids for
drooping, the eye movements for limitation or double vision,
the strength around the eyes and of facial movements, plus the
ability to look up for a sustained period of time to test for
fatigability of the eye and eyelid movements.
· In the throat the doctor might check for the tone of
the voice, the ability to talk for a sustained period, the ability
to hold a sung note, and the ability to safely swallow and drink.
The doctor might also examine the thyroid gland at the front
of the neck, and the strength of the neck in pushing the head
forward and back against resistance.
· In the arms and the legs the doctor might check for
the presence and symmetry of reflexes, strength in the muscles
particularly in those around the shoulder and hip, the ability
to do certain things such as rising from a chair without using
arms to help, and the presence of fatigability by checking strength
in one side for a sustained period and then comparing it after
that to the other side.
There are two special clinical tests that the doctor might perform
looking for MG. These are the ice test and the Tensilon test.
In the ice test the doctor will examine for improvement in eyelid
drooping after covering the eye for a minute or two with an
ice pack or a cold pack. In the Tensilon test the doctor will
examine for improvement in any weak area of the body after administration
of the medication Tensilon. This medication only works when
injected into the vein, and only has a short duration of effect.
Variations on this test include the injection of neostigmine,
and taking a tablet of Mestinon, again see if there is any improvement
of weakness. Obviously both the ice test and the Tensilon test
require something abnormal to be present at the time of the
test, in other words the tests cannot be done if there are no
abnormal findings on examination at the time.
Nerve Conduction Studies and Repetitive Stimulation
Nerve conduction studies can test both the sensory and the motor
nerves, in the context of MG generally only the motor nerves
are examined. An electrical stimulus (shock) is applied to the
skin overlying the nerve, the nerve then activates and sends
the signal to the muscle supplied by that nerve. The size of
the muscle response and the time that the nerve signal takes
to get there is recorded from a separate set of electrodes on
the skin over the muscle.
This test often frightens people but it sounds worse than it
actually is, and the doctor will generally have established
normal ranges on themselves and will know what it feels like.
In MG repetitive closely timed stimuli will often produce progressively
smaller or weaker responses in the muscle recording electrodes.
This is called Decrement of the Compound Muscle Action Potential
(CMAP) in the Repetitive Stimulation Test. It is the most specific
of the nerve tests for MG, but is not present in all cases and
is only able to be done on certain muscles, which may not be
affected in any individual patient. An example of decrement
on repetitive stimulation can be seen below, with progressive
decline in size (and therefore power) in the first four muscle
responses. This is the electrical, objective equivalent of the
fatigue that most patients with MG experience.
In some instances an electromyogram (EMG) will
also be performed, particularly if an alternative diagnosis
is being considered. An EMG involves placing a very tiny electrode
needle into the muscles, and the muscle will then be examined
both with the patient relaxing the muscle and with the patient
activating the muscle. Always let your doctor know if you are
on blood thinning agents, in particular warfarin, before having
this test as a more limited EMG test may be done in such circumstances.
For more detail on EMG results, see http://www.neuro.wustl.edu/neuromuscular/mtime/mgdx.html#rns)
Single Fibre EMG (SFEMG)
SFEMG is the most sensitive nerve test of neuromuscular transmission
and shows increased jitter in some muscles in almost all patients
with myasthenia gravis. SFEMG is like standard EMG in that a
small needle is inserted into the muscle. However it is technically
a much more difficult test for the doctor and often requires
a study of up to an hour long. For this reason generally the
other tests are done first, and SFEMG is used if the other tests
are normal but the diagnosis of MG is still suspected.
The concept of jitter and exactly what causes it can be difficult
to explain without a thorough knowledge of the nature of the
neuromuscular junction. Muscles are made up of thousands of
separate muscle (motor) units. Jitter can be thought of as a
measure of the fatigability within a microscopic single motor
unit itself, rather than within the muscle as a whole which
is tested with repetitive stimulation. The tiny needle is actually
inserted within a single motor unit.
Jitter is greatest in weak muscles but may be abnormal even
in muscles with normal strength. Patients with mild or purely
ocular muscle weakness may have increased jitter only in facial
muscles. Increased jitter is a nonspecific sign of abnormal
neuromuscular transmission and can be seen in other motor unit
diseases. Therefore the finding of increased jitter does not
definitely mean that MG is present. Normal jitter in a weak
muscle excludes abnormal neuromuscular transmission as the cause
Blood Test for Serum Antibodies
Blood tests can be performed to help in the diagnosis of MG.
This is not a routine blood test that a general practitioner
would necessarily do, and is not ordered as part of a routine
blood screen or during a routine medical. It can however be
done on a standard blood sample, although it is only done in
a few laboratories in Australia.
The standard MG blood test is the detection of serum antibodies
to the acetylcholine receptor (AChR antibodies). Antibodies
are proteins made by the immune system that are able to bind
specifically to other proteins. In the case of MG, the antibodies
bind to the acetylcholine receptor protein and block its function
or damage it. As the acetylcholine receptor protein is a normal
protein in the human body, the antibodies are often called autoantibodies
and MG is called an autoimmune disease.
AChR antibodies are only detectable in about 50% of patients
with MG confined to the eyes, and about 80% of patients with
generalised MG, where it affects not only the eyes but also
other parts of the body. This means that some patients with
MG are missed by this blood test, and therefore it cannot be
relied upon to detect all cases of MG. Technically this means
the ACHR test has impaired sensitivity for the diagnosis of
It should be noted that the concentration of AChR antibodies
varies widely among myasthenics, and that the level of concentration
does not predict the severity of the condition. Further, the
level of AChR antibodies may increase as the condition progresses.
AChR antibodies might very occasionally be elevated in people
with systemic lupus erythematosus, inflammatory neuropathy,
rheumatoid arthritis taking D-penicillamine, thymoma without
myasthenia gravis, mothers of children with arthrogryposis congenita,
and in relatives of patients with myasthenia gravis. However
often when these patients are carefully examined clinically
and with nerve tests they are found to have subtle MG without
having realised it. Technically this means the ACHR test has
relatively good but not perfect specificity.
The simple way to look at the ACHR antibody test is that an
elevated concentration of AChR antibodies confirms a clinical
diagnosis of MG, but a normal or negative result does not exclude
Around 20% of all myasthenics with generalised features have
no AChR antibodies detectable in their blood ("seronegative"
MG). About half of these patients have recently been shown to
have antibodies to another protein present at the neuromuscular
junction, called MuSK (muscle specific tyrosine kinase). The
role of the MuSK protein is still been clarified, but it seems
to be important in forming and maintaining the structure of
the neuromuscular junction. Antibodies to MuSK for patients
in Australasia and Southeast Asia can be tested at the Molecular
Medicine Laboratory, Concord Hospital, Sydney.
Comparison of Diagnostic
There is no one definitive test for MG. The doctor will do the
tests that are necessary for the exact clinical situation, but
each test has certain advantages and disadvantages that are
· Sometimes the diagnosis is obvious on the history and
clinical examination, although the doctor will generally also
want to tests to help guide treatment and provide for the monitoring
of the response to treatment
· the icepack test is simple and quick but only generally
useful when there is eyelid drooping
· The Tensilon test is useful when only ocular and oral
symptoms are present, but is not completely reliable and can
generally only be done in hospital.
· Detectable antibodies to ACHR or MuSK are highly diagnostic
of MG at the absence of such antibodies to is not exclude MG
· Decrement on repetitive nerve stimulation generally
confirms MG but is frequently normal in patients with mild or
purely ocular disease.
· The finding of increased jitter by SFEMG is the most
sensitive clinical test for abnormal neuromuscular transmission
and is abnormal in almost all patients with myasthenia gravis,
but it does not prove myasthenia gravis and is present in a
number of other conditions that affect the nerve and muscle
and that can cause symptoms similar to that of MG.
Sometimes all of these confirmatory tests are negative in someone
whose clinical examination seems to point to MG. In these cases,
the doctor would diagnose "possible MG" or "probable
MG". In this case a patient would be monitored to see if
the condition manifests itself and a diagnostic trial of treatment
may sometimes be given.