PBL Week 7

Myasthenia gravis is an autoimmune condition that affects the nerves and

muscles
In myasthenia gravis, the immune system produces antibodies (proteins) that
block or damage muscle receptor cells.
This prevents messages being passed from the nerve endings to the muscles,
which results in the muscles not contracting (tightening) and becoming weak
The most common age at onset is the second and third decades in women
and the seventh and eighth decades in men

Diagnosis

Blood Test
- A special type of blood test can be used to detect the antibodies (proteins)
that block or damage the muscle receptors
- Most people with myasthenia gravis have an abnormally high number of
acetylcholine receptor antibodies.
- The antibody blood tests are quite specific, which means they're almost
never detected in patients who don't have myasthenia gravis.
- A small amount people with myasthenia gravis may test negative for
acetylcholine receptor antibodies but have anti-MuSK antibodies instead
- The antibodies produced can be made in various parts of the body such as
the bone marrow, blood, lymph glands or the thymus gland
Nerve Conduction Tests
- Electromyography is a procedure that can be used to identify
communication problems between the nerves and muscles. It involves
inserting a needle electrode through the skin into the muscle.
- This produces an electrical recording of the muscle activity. If you have
myasthenia gravis, your muscles won't respond well to nerve stimulation.
Edrophonium test
- Injection of a type of medication called edrophonium chloride
- Edrophonium chloride prevents the substance acetylcholine from being
broken down
- In people with myasthenia gravis, the increased amount of acetylcholine
produces a sudden but temporary improvement in muscle power.
However, this won't usually occur in people with other causes of muscle
weakness.
- Edrophonium is a readily reversible acetylcholinesterase inhibitor. It
prevents breakdown of the neurotransmitter acetylcholine and acts by
competitively inhibiting the enzyme acetylcholinesterase, mainly at the
neuromuscular junction
- There are significant side effects associated with the
edrophonium test, such as heart rate and breathing problems,
that may occur during the investigation. For this reason, the test
is rarely performed. This test should only be considered if
myasthenia gravis is still suspected despite negative blood and
electrical tests. If performed, the test should only be carried out
by experienced neurology doctors in specialist centres with
resuscitation equipment available.
Imaging Tests

CT Scans or MRIs are used to detect for an enlarged Thymus gland or the
formation of a tumour on the Thymus.

The thymus gland, which lies in the chest area beneath the breastbone, plays
an important role in the development of the immune system in early life. Its
cells form a part of the body's normal immune system. The gland is
somewhat large in infants, grows gradually until puberty, and then gets
smaller and is replaced by fat with age. In adults with myasthenia gravis, the
thymus gland remains large and is abnormal Some individuals with
myasthenia gravis develop thymomas (tumours of the thymus gland).
The relationship between the thymus gland and myasthenia gravis is not yet
fully understood. Scientists believe the thymus gland may give incorrect
instructions to developing immune cells, ultimately resulting in autoimmunity
and the production of the acetylcholine receptor antibodies, thereby setting
the stage for the attack on neuromuscular transmission
Curare
- Curare is a common name for various plant extract alkaloid arrow poisons
originating from Central and South America. These poisons function by
competitively and reversibly inhibiting the nicotinic acetylcholine receptor
(nAChR), which is a subtype of acetylcholine receptor found at the
neuromuscular junction. This causes weakness of the skeletal muscles
and, when administered in a sufficient dose, eventual death by
asphyxiation due to paralysis of the diaphragm.
- Muscle paralysis can be reversed by administration of an
acetylcholinesterase inhibitor
Symptoms
- Ptosis drooping of the eyelids
- Blurred/Double vision
- General low facial weakness
- Difficult chewing and walking (Dysarthria)
- Swallowing difficulties (Dysphagia)
- Certain breathing difficulties especially when lying flat in bed or after
exercise
- Weakness of muscles of the arm, legs and neck
- Physical activity often leads to weakness
Treatment
- Medicines such as pyridostigmine, an acetylcholinesterase inhibitor,
prevent the breakdown of acetylcholine, an important chemical that helps
the muscles contract (tighten). These medicines tend to work best in mild
myasthenia gravis. They can improve muscle contractions and strength in
affected muscles. They're often used if the initial symptoms aren't too
severe but pyridostigmine isn't a suitable long-term treatment for most
people (side effects, such as stomach cramps, muscle twitching, diarrhoea
and nausea).
- Steroid tablets, such as prednisolone, are used at a low dose. The dose
can be increased gradually over time and is usually kept at a high dose for
several months until remission is achieved.
- Immunosuppressant medication may be prescribed if remission isn't
achieved or the high dose of prednisolone isn't suitable. This is usually
azathioprine, mycophenolate or methotrexate. These are used to help

achieve remission so the prednisolone dose can be reduced and

eventually stopped.
- In some cases of myasthenia gravis, surgery to remove the thymus gland
(a thymectomy) may be recommended
- In severe cases, patient breathing may have stopped and so they will need
to stay in an ICU at a hospital to try and fix the problem either with
plasmapheresis (plasma removed externally, harmful antibodies removed
then added again) and Intravenous immunoglobulin therapy (temporary
but takes healthy donated blood and injects the immunoglobulin from it)
- No Cure
While MG reportedly occurs in all ethnic groups, relative differences in disease
prevalence are yet to be determined. The disease is manifest from infancy to
old age and can occur in both genders although more women than men are
affected. Women usually present during childbearing age. Men typically
develop symptoms at a later age with a median age of onset in the seventh
decade.

Is there a progressive loss of AChR?

Its a progressive disorder. In early stages, myasthenia gravis primarily affects
muscles that control eye movement (extraocular muscles) and those that
control facial expression, chewing, and swallowing. If untreated, the disorder
may affect muscles that control breathing (respiration), causing acute
respiratory failure. Once can only assume this is due to more AChRs being
blocked over time around the body.
LambertEaton myasthenic syndrome

It is the result of an autoimmune reaction in which antibodies are formed

against presynaptic voltage-gated calcium channels, and likely other nerve
terminal proteins, in the neuromuscular junction
Affects the legs more than the arms, separating it from the similar Myasthenia
gravis
Often has an underlying malignancy, most commonly small cell lung
carcinoma making it paraneoplastic
In LEMS, antibodies against VGCC decrease the amount of calcium that can
enter the nerve ending, hence less acetylcholine can be released from the
neuromuscular junction. Apart from skeletal muscle, the autonomic nervous
system also requires acetylcholine neurotransmission; this explains the
occurrence of autonomic symptoms in LEMS