1. Myasthenia Gravis
By Matthias Mauer
MBC 115 Anatomy, Physiology, and
Coding of the Integumentary,
Musculoskeletal, and Nervous Systems
May 27, 2014

2. Background: What is Myasthenia
Gravis?
• Myasthenia gravis (MG) is a disease characterized by muscle
weakness that fluctuates, is exacerbated by physical exertion
and improves through rest (Trouth et. al, 2012)
• Myasthenia gravis results in weakness attributed to specific
muscle groups, with ocular muscle weakness being substantially
most common initial symptom
• Other muscle groups which can be affected include
▫ bulbar muscle(s)
▫ neck muscle(s)
▫ respiratory muscle(s)
▫ torso (thorax and abdomen)
▫ limbs

3. Background: Causes and Epidemiology
• Myasthenia gravis caused by impaired acetylcholine (AChR) receptor
stimulation in postsynaptic skeletal muscle membrane (Gilhus et. al, 2011)
• Root or external factors that cause myasthenia gravis are completely unknown
• Thymus is a critical organ for T-cell education and elimination of auto-reactive
T cells, and plays major role in myasthenia gravis (Angelini, 2011)
• It is likely that expression of AChRs by myoid cells in thymus, plus
inflammatory environment within MG thymus, contribute to induction and
maintenance of anti-acetylcholine receptor autoimmune response (Angelini,
2011)
• Myasthenia gravis is not very common with prevalence rates estimated to be
50-125 cases per million among world’s population (Angelini, 2011)

4. Basic Overview of the Neuromuscular
Junction and Acetylcholine Receptors for
Contraction of Skeletal Muscle
• Neuromuscular junction (NMJ):
communication synapse between nerve and
muscle which initiates muscle contraction
• Acetylcholine released into synaptic cleft on
nerve depolarization
• Muscle-specific tyrosine kinase (MuSK): an
AchR-associated protein involved in
clustering of AChRs during synapse
formation
• In healthy individuals, binding of
acetycholine to its receptor results in
generation of an action potential necessary
for muscle contraction (Angelini, 2011)

5. Characteristics of Myasthenia Gravis
• Only symptom of myasthenia gravis is muscle weakness
• Six subclassifications of myasthenia gravis according to specific
type of patient:
 Early-onset MG: age at onset <5 years
 Late-onset MG: age at onset <5 years, often with thymic atrophy,
mainly in males
 Thymoma-associated MG
 Ocular myasthenia gravis
 MG with no detectable AChR and muscle-specific tyrosine kinase
(MuSK) antibodies

6. Characteristics of Myasthenia Gravis
• Myasthenia gravis patients with thymoma almost always have
recognizable or noticeable AChR antibodies in serum (Trouth et. al,
2012)
• Thymoma-associated MG may also have additional paraneoplasia-
associated antibodies such as antivoltage-gated potassium and calcium
channels, anti-Hu, antidihydropyrimidinase-related protein 5, and
anti-glutamic acid decarboxylase antibodies (Trouth et. al, 2012)
• About 15% of myasthenia gravis patients do not have acetylcholine
receptor antibodies in their serum
▫ In 40% of this subgroup, antibodies to MuSK and another postsynaptic
neuromuscular junction (NMJ) protein are found (Trouth et. al, 2012)

7. Characteristics of Myasthenia
Gravis
• Disease onset generally occurs earlier
in females
• Ocular muscle weakness in
myasthenia gravis has characteristic
symptoms
• Eye muscle fatigue can actually cause
the diplopia in patient with MG

8. Characteristics of Myasthenia Gravis
• Other muscle weaknesses due to myasthenia
gravis in relation to different groups of muscles
are bulbar muscles, respiratory muscles, limbs,
facial muscles, and neck extensor and flexor
muscles resulting in following symptoms
 Fatigable chewing, especially when chewing
on solid food when bulbar muscles are
involved
 myasthenic crisis, a life threatening
condition, when respiratory muscle weakness
exists
 Proximal muscle weakness, with tendency of
arms to be more affected than legs if there is
limb weakness
 An expressionless face if facial muscles
affected
 Weight of head may overcome extensors
producing a “dropped head syndrome” if
symptom of neck muscle weakness exists

9. Pathophysiology of Myasthenia
Gravis
• Delayed diagnosis of myasthenia gravis is significant clinical problem because
patients’ health can decline to an extent that they can have a myasthenic crisis
• Myasthenic crisis is life-threatening condition in which weakness of
respiratory muscles become severe causing respiratory failure requiring
mechanical ventilation (Angelini, 2011)
• Generalized myasthenia gravis is when muscle weakness occurs in several
muscle groups of body or possibly all muscle groups of body
• Within two to three years, most individuals with myasthenia gravis develop
generalized MG
• Myasthenia gravis patients have increased risk of developing diseases of the
thyroid gland and other types of autoimmune diseases such as rheumatoid
arthritis and systemic lupus erythematosus (Angelini, 2011)

10. Diagnosis of Myasthenia Gravis
• Myasthenia gravis remains challenging disease to
diagnose because of its fluctuating nature and its
symptoms which are similar with other disorders
• Pharmacological testing is one way to diagnose
myasthenia gravis
• One of the pharmacological tests for MG is
 Tensilon (edrophonium chloride) test, an
acetylcholinesterase (AChE) inhibtor which inhibits
degradation of acetylcholine, thus providing prolonged
interaction of acetylcholine with reduced number of
acetylcholine receptors on muscle endplate (Angelini,
2011)

11. Diagnosis of Myasthenia Gravis
• Ice pack test is another way to diagnose myasthenia gravis
• Serological testing
• Electrophysiological tests-Repetitive nerve stimulation
study (RNS) and single fiber electromyography (SFEMG)
• RNS tests neuromuscular transmission
• Imaging tests, another way to diagnose myasthenia gravis,
are used to screen for possible thymoma or abnormal
thymus gland through a chest imaging study (computed
tomography or magnetic resonance imaging)

12. Treatment of Myasthenia Gravis
• Main objectives of treatment include remission of disease, hindering muscle
weakness from progressing, and maintaining muscle strength
• Symptomatic drugs such as acetylcholinesterase inhibitors act by increasing
amount of available acetylcholine at neuromuscular junction (Trouth et. al, 2012)
• Plasmapheresis, another type of drug therapy, improves strength in most
myasthenia gravis patients by directly removing acetycholine receptor from
circulation (Trouth et. al, 2012)
• Short-term immunomodulating therapies such as plasma exchange and
intravenous immunoglobulin are used in particular circumstances such as
myasthenic crisis and preoperatively before thymectomy or other surgical
procedures (Trouth et. al, 2012)
• Other drug therapies: long-term immune therapies, corticosteroids, and
nonsteroidal immunosuppressive agents such as mycophenolate mofetil and
azathioprine

13. Other Treatments for Myasthenia Gravis
• Anti-sense drug therapy currently being investigated as clinical development for several
different diseases including cancer, diabetes mellitus, and myasthenia gravis (one type of
anti-sense therapy drug is EN 101 [monransen]: shown to decrease production of
acetylcholine esterase production by hindering RNA from synthesizng and forming itself
into acetylcholine esterase protein)
• For patients with non-thymomatous autoimmune MG, thymectomy recommended only
as an option to increase clinical improvement or remission
• Surgical therapy for thymoma: removal of thymus performed with no exception
regardless of severity of myasthenia gravis
• During acute myasthenia gravis exacerbations, intensive care therapy with respiratory
support is performed (Gilhus et. al, 2011)
• Physical therapy is beneficial for reinvigorating muscle strength long-term

14. References
Angelini, C. (2011). Diagnosis and management of autoimmune myasthenia gravis.
Clinical Drug Investigation, 31(1), 1-14. Retrieved from http://web.b.ebscoho
st.com/ehost/detail?vid=7&sid=c25828da-0a0c-4ff6-bbab320bc8507fea%40
sessionmgr110&hid=128&bdata=JnNpdGU9ZWhvc3QtbGl2ZQ%3d%3d#
db=a9h&AN=57519942
Gilhus, N.E., Owe, J.F., Hoff, J.M., Romi, F., Skeie, G.O., & Aarli, J.A. (2011).
Myasthenia gravis: A review of available treatment approaches. Autoimmune
Diseases (2090-0422), 1-6. Retrieved from http://web.a.ebscohost.com/ehost/
detail?vid=10&sid=4587219a-884a-4195-997d-8e6784f5283c%40sessionmgr
4002&hid=4201&bdata=JnNpdGU9ZWhvc3QtbGl2ZQ%3d%3d#db=a9h&
AN=70697646
Trouth, A.J., Dabi, A., Solieman, N., Kurukumbi, M., & Kalyanam, J. (2012).
Myasthenia gravis: A review. Autoimmune Disease (2090-0422), 1-10.
Retrieved from http://web.b.ebscohost.com/ehost/detail?vid=13&sid=c258
28da-0a0c-4ff6-bbab320bc8507fea%40sessionmgr110&hid=128&bdata=Jn
NpdGU9ZWhvc3QtbGl2ZQ%3d%3d#db=a9h&AN=87286639