Myasthenia gravis (MG) is a neuromuscular disorder characterized by weakness and fatigability of skeletal muscles.
The underlying defect is a decrease in the number of available acetylcholine receptors (AChRs) at neuromuscular junctions due to an antibody-mediated autoimmune attack
2. Myasthenia gravis (MG) is a neuromuscular
disorder characterized by weakness and
fatigability of skeletal muscles.
The underlying defect is a decrease in the
number of available acetylcholine receptors
(AChRs) at neuromuscular junctions due to
an antibody-mediated autoimmune attack.
3. The hallmark of myasthenia gravis is muscle weakness
that worsen after period of activity and improves after
period of rest.
As a clinical entity, myasthenia gravis was not
recognized until Samuel Wilks in 1877 described bulbar
and peripheral muscular weakness. In the Lancet of June
2, 1934, the remarkable discovery of physostigmine
treatment by Dr. Mary Walker was published, which was
to become the mainstay of symptomatic treatment.
4. Certain muscles such as those that control eye and
eyelid movement, facial expression, chewing, talking,
and swallowing are often (but not always) involved in
the disorder. The muscle that control breathing and
neck and limb movements may also be affected.
There is no known cure but available treatments can
control the symptoms and often allow people to have
a relatively high quality of life.
5. In MG, the receptors at the muscle surface are destroyed
or deformed by antibodies that prevent a normal muscular
reaction from occurring.
The causative factor is unknown, but the disorder may
have a genetic link.
The most commonly affected muscles are those of the
eyes, face, and swallowing.
It can result in double vision, drooping eyelids, trouble
talking, and trouble walking.
Those affected often have a large thymus gland or develop
a thymoma.
6.
7. Factors that can worsen myasthenia
gravis
Fatigue
Illness
Stress
Extreme heat
Some medications — such as beta
blockers, calcium channel blockers,
quinine and some antibiotics
8. MG is rare, having a prevalence of 2–7 in 10,000.
Myasthenia Gravis is most common in the people at the
age of 40 and above.
This mainly affects the older people and the middle
aged people.
There are more women than men and the age of the
participants ranged from 40to 82.
The prevalence of this disease is found to be more in
China (64,942) followed by India (53,253) and is found
to be least in Bhutan (109).
9. The following table attempts to extrapolate the prevalence rate for
Myasthenia Gravis to the populations of various countries and regions
in Asia:
10. In MG, antibodies are directed toward the acetylcholine receptor
at the neuromuscular junction of the skeletal muscle
Resulting in:
Decreased number of acetylcholine receptors at the post synaptic muscle membrane
postsynaptic folds are simplified or flattened
Decreased neuromuscular transmission
Weakness of muscle contraction
Therefore, although Ach is released normally, it produces small end-plate potentials
that may fail to trigger muscle action potentials.
11. Failure of transmission at many
neuromuscular junctions results in
weakness of muscle contraction.
The amount of Ach released per impulse
normally declines on repeated activity
(termed presynaptic rundown).
14. An immune response to muscle-specific kinase
(musk), a protein involved in achR clustering at
neuromuscular junctions, can also result in
myasthenia gravis, with reduction of achRs
demonstrated experimentally.
The pathogenic antibodies are igG, and are t cell
dependent.
Immunotherapeutic strategies directed against either
the antibody-producing b cells or helper t cells are
effective in this antibody-mediated disease.
15. The autoimmune response is initiated and maintained in mg is not
completely understood, but the thymus appears to play a role in
this process.
The thymus is abnormal in ∼75% of patients with MG; in ∼65%
the thymus is “hyperplastic,” with the presence of active germinal
centers detected histologically, though the hyperplastic thymus is
not necessarily enlarged.
An additional 10% of patients have thymic tumors (thymomas).
Muscle-like cells within the thymus (myoid cells),
*Bear AChRs on their surface
*May serve as a source of autoantigen and trigger the
autoimmune reaction within the thymus gland.
16. Thymus gland, a part of your immune system located in the upper
chest beneath the breastbone, may trigger or maintain the production
of antibodies that result in the muscle weakness common in MG.
17. Myasthenia gravis may be inherited as a rare, genetic
disease, acquired by babies born to mothers with MG
Nerves communicate with the muscles by releasing
chemicals, called neurotransmitters.
Immune system produces antibodies that block or destroy
many of the muscles' receptor sites for a neurotransmitter
called acetylcholine.
With fewer receptor sites available, muscles receive fewer
nerve signals, resulting in weakness.
18. The main symptom of myasthenia gravis is weakness in
the voluntary skeletal muscles, which are muscles under
our control. The failure of muscles to contract normally
occurs because they can’t respond to nerve impulses.
Without proper transmission of the impulse, a blocked
communication occurs between nerve and muscle and
weakness results.
Weakness associated with myasthenia gravis typically
gets worse with more activity and improves with rest.
Some of the main symptoms to be noticed are:
19. In more than half the people who develop MG, their first signs
and symptoms involve eye problems:
Drooping of one or both eyelids (ptosis)
Double vision (diplopia)
Blurred vision, which may come and go
20. In about 15 percent of people with
myasthenia gravis, the first symptoms
involve face and throat muscles, which can
cause difficulties with:
› Speaking. The speech may be very soft
or sound nasal, depending upon which
muscles have been affected.
› Swallowing. May choke very easily,
which makes it difficult to eat, drink or
take pills. In some cases.
21. › Chewing. The muscles used for chewing may
wear out halfway through a meal, particularly if
eating.
› Facial expressions. Family members may note
"lost smile" if the muscles that control facial
expressions are affected
22. Myasthenia gravis can cause weakness in arms and legs, but
this usually happens in conjunction with muscle weakness in
other parts of the body – such as eyes, face or throat.
The disorder usually affects arms more often than legs.
If it affects legs, may waddle when walking.
Normal dumbbell Weakness dumbbell
23. If having trouble with:
Breathing
Seeing
Swallowing
Chewing
Walking
24. History Diplopia, ptosis, Weakness in characteristic
distribution, Fluctuation and fatigue: worse with
repeated activity, improved by rest Effects of previous
treatments .
Physical examination Ptosis, diplopia Motor power
survey: quantitative testing of muscle strength ,Forward
arm abduction time(5 min), Vital capacity, Absence of
other neurologic signs.
25. Edrophonium test:
Injection of the chemical edrophonium (Tensilon) may result
in a sudden, although temporary, improvement in muscle
strength — an indication that may have myasthenia gravis.
Edrophonium- acts to block an enzyme that breaks down
acetylcholine, the chemical that transmits signals from nerve
endings to muscle receptor sites.
Blood analysis: A blood test may reveal the presence of
abnormal antibodies that disrupt the receptor sites where
nerve impulses signal muscles to move.
26. Single-fiber electromyography (EMG):
EMG measures the electrical activity
traveling between brain and muscle. It
involves inserting a very fine wire electrode
through skin and into a muscle. In single-
fiber EMGs, a single muscle fiber is tested.
Imaging scans: CT scan or an MRI to
confirm a tumor or other abnormality in
thymus.
• SINGLE FIBER-EMG
• CT CHEST
27. A. THERAPEUTIC MANAGEMENT:
Cholinesterase inhibitors.
Drugs like pyridostigmine (Mestinon) enhance communication between
nerves and muscles.
These drugs don't cure, but improves muscle contraction and strength.
Corticosteroids.
These types of drugs inhibit the immune system, limiting antibody production.
Prolonged use of corticosteroids, can lead to serious side effects, like bone
thinning, weight gain, diabetes, increased risk of some infections, and increase
and redistribution of body fat.
Immunosuppressants.
Doctor may also prescribe other medications that alter immune system, like
azathioprine (Imuran), cyclosporine (Sandimmune)
28. Plasmapheresis. This procedure uses a filtering process
similar to dialysis. Blood is routed through a machine that
removes the antibodies that are blocking transmission of
signals from nerve endings to muscles' receptor sites.
However, the beneficial effects usually last only a few
weeks.
Intravenous immune globulin. This therapy provides body
with normal antibodies, which alters immune system
response. It has a lower risk of side effects than do
plasmapheresis and immune-suppressing, but it can take a
week or two to start working and the benefits usually last
less than a month or two.
29. Thymectomy - surgical removal
of the thymus gland. The role of
the thymus gland in MG is not
fully understood, and the
thymectomy may or may not
improve a child's symptoms.
30. Because the cause of myasthenia gravis is unknown, there is
no way to prevent it. However, once the disease has
developed, there may be ways to prevent episodes of
worsening symptoms or flare-ups:
Give yourself plenty of rest.
Avoid strenuous, exhausting activities.
Avoid excessive heat and cold.
Avoid emotional stress.
31. Whenever possible, avoid exposure to any kind of
infection, including colds and influenza (flu). You
should be vaccinated against common infections,
such as influenza.
Work with your doctor to monitor your reactions to
prescription medications. Some drugs commonly
prescribed for other problems, such as infections,
heart disease or hypertension, may make myasthenia
gravis worse. You may need to choose alternative
therapies or avoid some medications entirely.
32. Harrisons Neurology in clinical medicine
http://www.ninds.nih.gov/disorders/myasthenia_gravis/detai
l_myasthenia_gravis.htm ( for fact sheet & possible
questions asked by patient’s family )
http://www.drugs.com/health-guide/myasthenia-gravis.html
https://en.wikipedia.org/wiki/Myasthenia_gravis
Myasthenia Gravis A Manual for the Health Care
Provider, Jemes F. Haward, M. D