Myasthenia gravis

Myasthenia gravis (from Greek μύς “muscle”, ἀσθέ- subtype evolves into generalized MG, usually after a few
νεια “weakness”, and Latin: gravis “serious"; abbrevi- years.[6]
ated MG) is a neuromuscular disease that leads to fluc-
tuating muscle weakness and fatigue. In the most com-
mon cases, muscle weakness is caused by circulating 1.2 Eating
antibodies that block acetylcholine receptors at the post-
synaptic neuromuscular junction, inhibiting the excita- Weakness of the muscles involved in swallowing may
tory effects of the neurotransmitter acetylcholine on nico-
lead to swallowing difficulty (dysphagia). Typically, this
tinic receptors at neuromuscular junctions. Alternatively,
means that some food may be left in the mouth after
in a much rarer form, muscle weakness is caused by a ge-an attempt to swallow,[7] or food and liquids may re-
netic defect in some portion of the neuromuscular junc- gurgitate into the nose rather than go down the throat
tion that is inherited at birth as opposed to developing(velopharyngeal insufficiency).[4] Weakness of the mus-
through passive transmission from the mother’s immune cles that move the jaw (muscles of mastication) may
system at birth or through autoimmunity later in life.[1]
cause difficulty chewing. In individuals with MG, chew-
Myasthenia is treated with medications such as ing tends to become [3]
more tiring when chewing tough,
acetylcholinesterase inhibitors or immunosuppressants, fibrous foods. Difficulty in swallowing, chewing and
and, in selected cases, thymectomy (surgical removal of speaking is the first symptom in about one-sixth of
[3]
the thymus gland). The disease is diagnosed in 3 to 30 individuals.
people per million per year.[2] Diagnosis is becoming
more common due to increased awareness.[2]
1.3 Voice

Weakness of the muscles involved in speaking may lead

1 Signs and symptoms to dysarthria and hypophonia.[3] Speech may be slow
and slurred,[8] or have a nasal quality.[4] In some cases
The initial, main symptom in MG is painless weakness of a singing hobby or profession must be abandoned.[7]
specific muscles, not fatigue.[3] The muscle weakness be-
comes progressively worse during periods of physical ac-
tivity, and improves after periods of rest. Typically, the 1.4 Head and neck
weakness and fatigue are worse towards the end of the
day.[4] MG generally starts with ocular (eye) weakness; Due to weakness of the muscles of facial expression and
it might then progress to a more severe generalized form, muscles of mastication, there may be facial weakness,
characterized by weakness in the extremities or while per- manifesting as inability to hold the mouth closed[3] (the
forming basic life functions.[5] “hanging jaw sign”), and a snarling appearance when at-
tempting to smile.[4] Together with drooping eyelids, fa-
cial weakness may make the individual appear sleepy
1.1 Eyes or sad.[3] There may be difficulty in holding the head
upright.[8]
In about two-thirds of individuals, the initial symptom
of MG is related to the muscles around the eye.[3] There
may be eyelid drooping (ptosis due to weakness of levator 1.5 Other
palpebrae superioris)[6] and double vision (diplopia,[3]
due to weakness of the extraocular muscles).[4] Eye The muscles that control breathing (dyspnea) and limb
symptoms tend to get worse when watching television, movements can also be affected, but rarely do these
reading or driving, particularly in bright conditions.[3] present as the first symptoms of MG, and they develop
Consequently, some affected individuals choose to wear over months to years.[9] In a myasthenic crisis, a paralysis
sunglasses.[3] The term “ocular myasthenia gravis” de- of the respiratory muscles occurs, necessitating assisted
scribes a subtype of MG where muscle weakness is con- ventilation to sustain life.[10] Crises may be triggered by
fined to the eyes, i.e. extraocular muscles, levator palpe- various biological stressors such as infection, fever, an ad-
brae superioris and orbicularis oculi.[6] Typically, this verse reaction to medication, or emotional stress.[10]

1
2 3 PATHOPHYSIOLOGY

2 Cause
This neuromuscular disease is caused by transmission de-
fects in nerve impulses to muscles. The neuromuscu-
lar junction is apparently affected: acetylcholine, which
produces muscle contraction under normal conditions no
longer produces the contractions necessary to muscle
movement.[11]

3 Pathophysiology

The nicotinic acetylcholine receptor

other autoimmune diseases. Relatives of MG patients

have a higher percentage of other immune disorders.[13]
The thymus gland cells form part of the body’s immune
system. In those with myasthenia gravis, the thymus
gland is large and abnormal. It sometimes contains clus-
ters of immune cells which indicate lymphoid hyperpla-
sia, and it is believed the thymus gland may give wrong
instructions to immune cells.[14]

3.1 Associated conditions

Myasthenia gravis is associated with various autoimmune
Neuromuscular junction: 1. Axon 2. Muscle cell membrane
diseases, including:
3. Synaptic vesicle 4. Nicotinic acetylcholine receptor 5.
Mitochondrion • Thyroid diseases,[15]
• CNS disease[16]
• Lupus[17]

3.2 In pregnancy
For women who are pregnant and already have MG, in a
third of cases they have been known to experience an ex-
acerbation of their symptoms, and in those cases it usu-
ally occurs in the first trimester of pregnancy.[18] Signs
and symptoms in pregnant mothers tend to improve dur-
ing the second and third trimesters. Complete remission
can occur in some mothers.[19] Immunosuppressive ther-
apy should be maintained throughout pregnancy, as this
A juvenile thymus shrinks with age. reduces the chance of neonatal muscle weakness, as well
as controls the mother’s myasthenia.[20]
Myasthenia gravis is believed to be caused by variations
10-20% of infants with mothers affected by the con-
in certain genes. The disorder occurs when the immune dition are born with Transient Neonatal Myasthenia,
system malfunctions and attacks the body’s tissues. The
which generally produces feeding and respiratory diffi-
antibody in myasthenia gravis attacks normal human pro-
culties that develop within 12 hours to several days af-
tein, targeting a protein called an acetylcholine receptor,
ter birth.[18][20] A child with TNM typically responds
or a related protein called a muscle-specific kinase.[12]
very well to acetylcholinesterase inhibitors, and the con-
Human leukocyte antigens have been associated with MG dition generally resolves over a period of three weeks as
receptibility. Many of these genes are present among the antibodies degregate and generally does not result in
4.4 Electrodiagnostics
any complications.[18] Very rarely, an infant can be born
with arthrogryposis multiplex congenita, secondary to
profound intrauterine weakness. This is due to maternal
antibodies that target an infant’s acetylcholine receptors.
In some cases, the mother remains asymptomatic.[20]
4 Diagnosis
MG can be difficult to diagnose, as the symptoms can be
subtle and hard to distinguish from both normal variants
and other neurological disorders.[7]
Three types of myasthenic symptoms in children can be 4.4
distinguished:[21]
1. Transient Neonatal: occurs in 10 to 15% of babies
born to mothers afflicted with the disorder, and dis-
appears after a few weeks.
2. Congenital: the rarest form; genes are present in
both parents.
3. Juvenile myasthenia gravis: most common in fe-
males
Congenital myasthenias cause muscle weakness and fati-
gability similar to those of MG. The signs of congen-
ital myasthenia usually are present in the first years of
A chest CT-scan showing a thymoma (red circle)
childhood although they may not be recognized until
adulthood.[22]
4.1 Classification
When diagnosed with MG, a person is assessed for his
or her neurological status and the level of illness is estab-
lished. This is usually done using the accepted Myasthe-
nia Gravis Foundation of America Clinical Classification
scale, which is as follows:
4.2 Physical examination
During a physical examination to check for MG, a proc-
tor might ask the potentially affected person to look at
a fixed point for 30 seconds and to relax the muscles of
their forehead. This is done because a person with MG
and ptosis of their eyes might be involuntarily using their
forehead muscles to compensate for the weakness in their
eyelids.[7] The clinical examiner might also try to elicit the
“curtain sign” in a patient by holding one of the person’s
eyes open, which in the case of MG will lead the other
eye to close.[7]
4.3 Blood tests
If the diagnosis is suspected, serology can be performed:
3
• One test is for antibodies against the acetylcholine
receptor,[7] the test has a reasonable sensitivity of
80–96%, but in ocular myasthenia, the sensitivity
falls to 50%.
• A proportion of the patients without antibodies
against the acetylcholine receptor have antibodies
against the MuSK protein.[24]
• In specific situations, testing is performed for
Lambert-Eaton syndrome.[25]
Electrodiagnostics
Photograph of a patient showing right partial ptosis (left picture),
the left lid shows compensatory pseudo lid retraction because of
equal innervation of the levator palpabrae superioris (Hering’s
law of equal innervation): Right picture: after an edrophonium
test, note the improvement in ptosis.
Muscle fibers of patients with MG are easily fatigued,
and a test called the repetitive nerve stimulation test can
be performed. In single-fiber electromyography, which
is considered to be the most sensitive (although not the
most specific) test for MG,[7] a thin needle electrode is in-
serted into different areas of a particular muscle to record
the action potentials from several samplings of different
individual muscle fibers. Two muscle fibers belonging
to the same motor unit are identified, and the temporal
variability in their firing patterns is measured. Frequency
and proportion of particular abnormal action potential
patterns, called “jitter” and “blocking”, are diagnostic.
Jitter refers to the abnormal variation in the time inter-
val between action potentials of adjacent muscle fibers
in the same motor unit. Blocking refers to the failure of
nerve impulses to elicit action potentials in adjacent mus-
cle fibers of the same motor unit.[26]
4 5 MANAGEMENT

4.5 Ice test

Applying ice for two to five minutes to the muscles re-

portedly has a sensitivity and specificity of 76.9% and
N O
98.3%, respectively, for the identification of MG. Acetyl-
cholinesterase is thought to be inhibited at the lower tem- N
perature, and this is the basis for this diagnostic test. This
generally is preformed on the eyelids when a ptosis is
present and is deemed positive if there is a ≥2mm raise
O
in the eyelid after the ice is removed.[27]

Neostigmine, chemical structure

4.6 Edrophonium test

This test requires the intravenous administration of

edrophonium chloride or neostigmine, drugs that block
the breakdown of acetylcholine by cholinesterase O
N
(acetylcholinesterase inhibitors).[28] This test is no longer
typically preformed as its use can lead to life-threatening
bradycardia (slow heart rate) which requires immediate
emergency attention.[29] Production of edrophonium was N
discontinued in 2008.[10]

N O
4.7 Imaging

S
A chest X-ray may identify widening of the mediastinum
suggestive of thymoma, but computed tomography or
magnetic resonance imaging (MRI) are more sensitive
ways to identify thymomas and are generally done for this

N
reason.[30] MRI of the cranium and orbits may also be
performed to exclude compressive and inflammatory le-
sions of the cranial nerves and ocular muscles.[31]

H
4.8 Pulmonary function test
N
The forced vital capacity may be monitored at intervals to
detect increasing muscular weakness. Acutely, negative N
N
inspiratory force may be used to determine adequacy
of ventilation; it is performed on those individuals with
MG.[32][33]

Azathioprine, chemical structure

5 Management
Treatment is by medication and/or surgery. Med-
ication consists mainly of acetylcholinesterase in-
hibitors to directly improve muscle function and
immunosuppressant drugs to reduce the autoimmune
process.[34] Thymectomy is a surgical method to treat
MG.[35]
5.1 Medication
Acetylcholinesterase inhibitors can provide symptomatic
benefit and may not fully remove a person’s weakness
from MG.[36] While they might not fully remove all symp-
toms of MG, they still may allow a person the ability
to perform normal daily activities.[36] Usually, acetyl-
cholinesterase inhibitors are started at a low dose and in-
creased until the desired result is achieved. If taken 30
minutes before a meal, symptoms will be mild during eat-
ing, which is helpful for those who have difficulty swal-
lowing due to their illness. Another medication used for
MG is atropine.[37] Pyridostigmine is a short-lived drug,
with a half-life of about four hours with relativity few side
effects.[38] Generally, it is discontinued in those who are
being mechanically ventilated as it is known to increase
the amount of salivary secretions.[38] There have been few

high-quality studies directly comparing cholinesterase in-
hibitors with other treatments (or placebo); it has been
suggested that their practical benefit is such that it would
be difficult to conduct studies in which they would be
withheld from some people.[39] The steroid prednisone
might also be utilized to achieve a better result, but it can
lead to the worsening of symptoms for 14 days and take
6–8 weeks for it to achieve its maximal effectiveness.[38]
Due to the myriad of symptoms steroid treatments can
have, it is not the preferred method of treatment.[38]
5.2 Plasmapheresis and IVIG
If the myasthenia is serious (myasthenic crisis),
plasmapheresis can be used to remove the putative
antibodies from the circulation. Also, intravenous
immunoglobulins (IVIGs) can be used to bind the
circulating antibodies. Both of these treatments have
relatively short-lived benefits, typically measured in
weeks, and often are associated with high costs which
make them prohibitive; they are generally reserved for
when MG requires hospitalization.[38][40]
5.3 Surgery
Main article: Thymectomy
As thymomas are seen in 10% of all people with the MG,
patients are often given a chest X-ray and CT scan to eval-
uate their need for surgical removal of their thymus and
any cancerous tissue that may be present.[10][29] Even if
surgery is performed to remove a thymoma, it generally
does not lead to the remission of MG.[38] Surgery in the
case of MG involves the removal of the thymus although
there is no clear consensus that it would be beneficial ex-
cept in the presence of a thymoma. However, thymec-
tomy should not be done in ocular myasthenia.[41] Cur-
rently, there is no literature that gives meaningful con-
clusions in regard to the benefit of thymectomy in af-
fected individuals. Some observational studies indicate
that thymectomy could be prudent in MG.[41]
5.4 Physical measures
Patients with MG should be educated regarding the fluc-
tuating nature of their symptoms, including weakness and
exercise-induced fatigue. Exercise participation should
be encouraged with frequent rest.[42] In people with gen-
eralized MG, some evidence indicates a partial home
program including training in diaphragmatic breathing,
pursed lip breathing, and interval-based muscle therapy
may improve respiratory muscle strength, chest wall mo-
bility, respiratory pattern, and respiratory endurance.[43]
5
6 Prognosis
The prognosis of MG patients is generally good, as is
quality of life, given very good treatment.[44] In the
early 1900s the mortality associated with MG was 70%;
now that number is estimated to be around 3–5% which
is attributed to increased awareness and medications
to manage symptoms.[38] Monitoring of a person with
MG is very important as at least 20% of people diag-
nosed with it will experience a myasthenic crisis within
two years of their diagnosis requiring emergent medical
intervention.[38] Generally, the most disabling period of
MG might be years after the initial diagnosis.[36]
7 Epidemiology
Myasthenia gravis occurs in all ethnic groups and both
sexes. It most commonly affects women under 40 and
people from 50 to 70 years old of either sex, but it has
been known to occur at any age. Younger patients rarely
have thymoma. The prevalence in the United States is
estimated between 0.5–20.4 cases per 100,000, with an
estimated 60,000 Americans affected.[10][45] Within the
United Kingdom, it is estimated that there are 15 cases
of MG per 100,000 people.[29]
8 History
The first to write about MG were Thomas Willis,
Samuel Wilks, Erb, and Goldflam.[6] The term “myas-
thenia gravis pseudo-paralytica” was proposed in 1895
by Jolly, a German physician.[6] Mary Walker treated a
person with MG with physostigmine in 1934.[6] Simp-
son and Nastuck detailed the autoimmune nature of the
condition.[6] In 1973, Patrick and Lindstrom used rab-
bits to show that immunization with purified muscle-like
acetylcholine receptors caused the development of MG-
like symptoms.[6]
9 Research
Immunomodulating substances, such as drugs that pre-
vent acetylcholine receptor modulation by the immune
system, are currently being researched.[46] Some research
recently has been on anti-c5 inhibitors for treatment re-
search as they are safe and used in the treatment of
other diseases.[47] Ephedrine seems to benefit some peo-
ple more than other medications, but it has not been prop-
erly studied as of 2014.[48][49]
6 11
10 Notable cases
• Indian actor Amitabh Bachchan was diagnosed with
it in 1983.
• Brandon Cox, starting Auburn quarterback from
2005-2007, finished with a record of 29-9.[50]
• Christopher Robin Milne, the son of A. A. Milne,
author of the Winnie-the-Pooh books and the person
on whom Christopher Robin was based, lived with
myasthenia gravis for several years before his death
in 1996.[51]
• Actor Roger Smith, husband of Ann-Margret, was
diagnosed in 1980.[52]
• Days Of Our Lives actress Suzanne Rogers has
the condition and so does the character she plays,
Maggie Horton.
• Powhatan chief Opchanacanough (Uncle of
Pocahontas ) was thought to have the condition.
• Stephen Garrett, also known as Static Major. He
made up half of the R&B group “Playa”.
11 References
[1] Kandel E, Schwartz J, Jessel T, Siegelbaum S, Hudspeth A
(2012). Principles of Neural Science (5 ed.). pp. 318–19.
[2] McGrogan A, Sneddon S, de Vries CS (2010). “The
incidence of myasthenia gravis: a systematic litera-
ture review”. Neuroepidemiology 34 (3): 171–183.
doi:10.1159/000279334. PMID 20130418.
[3] Engel AG (3 April 2012). Myasthenia Gravis and Myas-
thenic Disorders (2nd ed.). Oxford University Press, USA.
pp. 109–110. ISBN 978-0-19-973867-0.
[4] Scully C (21 July 2014). Scully’s Medical Problems in Den-
tistry. Elsevier Health Sciences UK. ISBN 978-0-7020-
5963-6.
[5] “Myasthenia Gravis: Practice Essentials, Background,
Anatomy”. 2015-06-06.
[6] Nair, AG; Patil-Chhablani, P; Venkatramani, DV;
Gandhi, RA (October 2014). “Ocular myasthenia
gravis: a review.”. Indian journal of ophthalmology 62
(10): 985–91. doi:10.4103/0301-4738.145987. PMC
4278125. PMID 25449931.
[7] Scherer K, Bedlack RS, Simel DL. (2005). “Does this
patient have myasthenia gravis?". JAMA 293 (15): 1906–
14. doi:10.1001/jama.293.15.1906. PMID 15840866.
[8] Rajendran A; Sundaram S (10 February 2014). Shafer’s
Textbook of Oral Pathology (7th ed.). Elsevier Health Sci-
ences APAC. p. 867. ISBN 978-81-312-3800-4.
[9] “Myasthenia gravis: MedlinePlus Medical Encyclopedia”.
www.nlm.nih.gov. Retrieved 2015-07-09.
REFERENCES
[10] Marx, John A. Marx (2014). Rosen’s emergency medicine :
concepts and clinical practice (8th ed.). Philadelphia, PA:
Elsevier/Saunders. pp. 1441–1444. ISBN 1455706051.
[11] Information, National Center for Biotechnology; Pike, U.
S. National Library of Medicine 8600 Rockville; MD,
Bethesda; Usa, 20894. “Myasthenia Gravis - National Li-
brary of Medicine”. PubMed Health. Retrieved 2015-07-
09.
[12] “Myasthenia gravis”. Genetics Home Reference. Retrieved
2015-07-10.
[13] Sathasivam, Sivakumar (January 1, 2014). “Diagnosis
and management of myasthenia gravis”. Progress
in Neurology and Psychiatry 18 (1): 6–14.
doi:10.1002/pnp.315. ISSN 1931-227X.
[14] “Myasthenia Gravis Fact Sheet: National Institute of Neu-
rological Disorders and Stroke (NINDS)". www.ninds.
nih.gov. Retrieved 2015-07-10.
[15] “Autoimmune Myasthenia Gravis and Thyroid Disease in
Argentina (P02.200) -- Bettini et al. 80 (1001): P02.200
-- Neurology”. www.neurology.org. Retrieved 2015-07-
10.
[16] Kaminski, Henry J. (2009-03-02). Myasthenia Gravis
and Related Disorders. Springer Science & Business Me-
dia. ISBN 9781597451567.
[17] Jallouli, M.; Saadoun, D.; Eymard, B.; Leroux, G.;
Haroche, J.; Le Thi Huong, D.; De Gennes, C.; Chapelon,
C.; Benveniste, O. (Jul 2012). “The association of sys-
temic lupus erythematosus and myasthenia gravis: a series
of 17 cases, with a special focus on hydroxychloroquine
use and a review of the literature”. Journal of Neurology
259 (7): 1290–1297. doi:10.1007/s00415-011-6335-z.
ISSN 1432-1459. PMID 22160434. – via ScienceDirect
(Subscription may be required or content may be available
in libraries.)
[18] Varner, Michael (June 2013). “Myasthenia Gravis
and Pregnancy”. Clinical Obstetrics and Gynecology
(Lippincott Williams & Wilkins) 56 (2): 372–81.
doi:10.1097/GRF.0b013e31828e92c0.
[19] Téllez-Zenteno JF, Hernández-Ronquillo L, Salinas V,
Estanol B, da Silva O (2004). “Myasthenia gravis and
pregnancy: clinical implications and neonatal outcome”.
BMC Musculoskeletal Disorders 5: 42. doi:10.1186/1471-
2474-5-42. PMC 534111. PMID 15546494. Retrieved
10 July 2008.
[20] Warrell, David A; Timothy M Cox et al. (2003). Oxford
Textbook of Medicine — Fourth Edition — Volume 3. Ox-
ford. p. 1170. ISBN 0-19-852787-X.
[21] Rudd, Kathryn; Kocisko, Diane (2013-10-10). Pediatric
Nursing: The Critical Components of Nursing Care. F.A.
Davis. ISBN 9780803640535.
[22] “Congenital Myasthenia Information Page: National In-
stitute of Neurological Disorders and Stroke (NINDS)".
www.ninds.nih.gov. Retrieved 2015-07-11.

[23] Wolfe, Gil I.; Barohn, Richard J. (2009). “Myasthenia
Gravis: Classification and Outcome Measurements”.
Myasthenia Gravis and Related Disorders. Current Clin-
ical Neurology (Humana Press): 293–302. ISBN 978-1-
58829-852-2.
[24] Leite MI, Jacob S, Viegas S et al. (July 2008).
“IgG1 antibodies to acetylcholine receptors in 'seroneg-
ative' myasthenia gravis”. Brain 131 (Pt 7): 1940–
52. doi:10.1093/brain/awn092. PMC 2442426. PMID
18515870.
[25] “Lambert-Eaton syndrome: MedlinePlus Medical Ency-
clopedia”. www.nlm.nih.gov. Retrieved 2015-07-11.
[26] Selvan VA. (2011). “Single-fiber EMG: A review”. Ann
Indian Acad Neurol. 14 (1): 64–67. doi:10.4103/0972-
2327.78058. PMC 3108086. PMID 21654930.
[27] Kearsey, Christopher; Fernando, Prabhath; D'Costa,
Domnick; Ferdinand, Phillip (June 1, 2010). “The use
of the ice pack test in myasthenia gravis”. JRSM Short Re-
ports 1 (1): 14. doi:10.1258/shorts.2009.090037. ISSN
2054-2704. PMID 21103106.
[28] “Tensilon test: MedlinePlus Medical Encyclopedia”.
www.nlm.nih.gov. Retrieved 2015-07-11.
[29] Spillane, J.; Higham, E.; Kullmann, D. M. (21 De-
cember 2012). “Myasthenia gravis”. The BMJ 345:
e8497. doi:10.1136/bmj.e8497. ISSN 1756-1833.
PMID 23261848.
[30] de Kraker M, Kluin J, Renken N, Maat AP, Bogers AJ
(2005). “CT and myasthenia gravis: correlation be-
tween mediastinal imaging and histopathological find-
ings”. Interact Cardiovasc Thorac Surg 4 (3): 267–71.
doi:10.1510/icvts.2004.097246. PMID 17670406.
[31] Allan H. Ropper, Robert H. Brown Adams and Victor’s
Principles of Neurology McGraw-Hill Professional; 8 edi-
tion (29 March 2005)
[32] “Pulmonary function tests: MedlinePlus Medical Ency-
clopedia”. www.nlm.nih.gov. Retrieved 2015-07-11.
[33] “Emergent Management of Myasthenia Gravis:
Overview, Patient History, Physical Examination”.
2015-06-06.
[34] Mehndiratta, Man Mohan; Pandey, Sanjay; Kuntzer,
Thierry (2014). “Acetylcholinesterase inhibitor
treatment for myasthenia gravis”. The Cochrane
Database of Systematic Reviews 10: CD006986.
doi:10.1002/14651858.CD006986.pub3. ISSN 1469-
493X. PMID 25310725.
[35] “National Guideline Clearinghouse | Practice parame-
ter: thymectomy for autoimmune myasthenia gravis (an
evidence-based review). Report of the Quality Standards
Subcommittee of the American Academy of Neurology.”.
www.guideline.gov. Retrieved 2015-07-11.
[36] Mehndiratta, Man Mohan; Pandey, Sanjay; Kuntzer,
Thierry (2014-10-13). Acetylcholinesterase inhibitor
treatment for myasthenia gravis. John Wiley & Sons, Ltd.
doi:10.1002/14651858.CD006986.pub3.
7
[37] Choices, N. H. S. (2014). “Atropine - Myasthenia-gravis
medicines and drugs - NHS Choices”. Retrieved 2015-
07-11.
[38] Kumar, Vikas; Kaminski, Henry J. (7 October 2010).
“Treatment of Myasthenia Gravis”. Current Neu-
rology and Neuroscience Reports 11 (1): 89–96.
doi:10.1007/s11910-010-0151-1. ISSN 1528-4042.
[39] Mehndiratta, MM; Pandey, S; Kuntzer, T (Oct 13, 2014).
“Acetylcholinesterase inhibitor treatment for myasthenia
gravis.”. The Cochrane database of systematic reviews 10:
CD006986. doi:10.1002/14651858.CD006986.pub3.
PMID 25310725.
[40] Juel VC (2004). “Myasthenia gravis: management of
myasthenic crisis and perioperative care”. Semin Neu-
rol 24 (1): 75–81. doi:10.1055/s-2004-829595. PMID
15229794.
[41] “Surgical removal of the thymus for myasthenia gravis
that is not caused by a tumour of the thymus | Cochrane”.
www.cochrane.org. Retrieved 2015-07-11.
[42] Goldenberg, W.D. and Shah, A.K. “Myasthenia Gravis”.
eMedicine. Retrieved 5 May 2012.
[43] Cup E.H., Pieterse A.J., ten Broek-Pastoor J.M.,
Munneke M., van Engelen B.G., Hendricks H.T., van
der Wilt G.J., Oostendorp R.A., EH; Pieterse, AJ; Ten
Broek-Pastoor, JM; Munneke, M; Van Engelen, BG; Hen-
dricks, HT; Van Der Wilt, GJ; Oostendorp, RA (2007).
“Exercise therapy and other types of physical therapy
for patients with neuromuscular diseases: a systematic
review”. Archives of Physical Medicine and Rehabilita-
tion 88 (11): 1452–64. doi:10.1016/j.apmr.2007.07.024.
PMID 17964887.
[44] Sieb, J P (2014). “Myasthenia gravis: an update for the
clinician”. Clinical and Experimental Immunology 175
(3): 408–418. doi:10.1111/cei.12217. ISSN 0009-9104.
PMC 3927901. PMID 24117026.
[45] Cea, Gabriel; Benatar, Michael; Verdugo, Renato J; Sali-
nas, Rodrigo A (November 14, 2013). “Thymectomy
for non-thymomatous myasthenia gravis”. Cochrane
Database of Systematic Reviews (John Wiley & Sons, Ltd).
[46] Losen M, Martínez-Martínez P, Phernambucq M, Schu-
urman J, Parren PW, DE Baets MH (2008). “Treatment
of myasthenia gravis by preventing acetylcholine receptor
modulation”. Annals of the New York Academy of Sci-
ences 1132: 174–9. doi:10.1196/annals.1405.034. PMID
18567867.
[47] Conti-Fine, Bianca; Milani, Monica (December 1, 2006).
“Myasthenia gravis: past, present, and future”. The Jour-
nal of Clinical Investigation. doi:10.1172/JCI29894.
[48] Vrinten, C; van der Zwaag, AM; Weinreich, SS;
Scholten, RJ; Verschuuren, JJ (17 December 2014).
“Ephedrine for myasthenia gravis, neonatal myas-
thenia and the congenital myasthenic syndromes.”.
The Cochrane database of systematic reviews 12:
CD010028. doi:10.1002/14651858.CD010028.pub2.
PMID 25515947.
8 13 FURTHER READING

[49] Vrinten, Charlotte; van der Zwaag, Angeli M; Weinreich,

Stephanie S; Scholten, Rob JPM; Verschuuren, Jan JGM
(December 17, 2014). “Ephedrine for myasthenia gravis,
neonatal myasthenia and the congenital myasthenic syn-
dromes”. Cochrane Database of Systematic Reviews (John
Wiley & Sons, Ltd).

[50] Nielsen, Chad. “Toughness is a Choice”. ESPN Magazine.

Retrieved 11 November 2010.

[51] “Who Was Christopher Robin Milne?". 2007-06-18. Re-

trieved 2015-07-12.

[52] “Hollywood Legend Ann-Margret on Faith, Love and Re-

covery”. Retrieved 2015-07-12.

12 External links
• The Myasthenia Gravis Foundation of America
• The Myasthenia Gravis Association (MGA) for the
United Kingdom
• The Myasthenia Gravis Association (MGA) for the
Republic of Ireland
• The Myasthenia Gravis Coalition of Canada

13 Further reading
• Zhang, Zhenchang; Guo, Jia; Su, Gang; Li,
Jiong; Wu, Hua; Xie, Xiaodong (Novem-
ber 17, 2014). “Evaluation of the Quality
of Guidelines for Myasthenia Gravis with the
AGREE II Instrument”. PLoS ONE 9 (11):
e111796. doi:10.1371/journal.pone.0111796.
PMC 4234220. PMID 25402504.

• “NCBI - Diagnostic”. www.ncbi.nlm.nih.gov. Re-

trieved 2015-07-11.
 9

14 Text and image sources, contributors, and licenses

14.1 Text
• Myasthenia gravis Source: https://en.wikipedia.org/wiki/Myasthenia_gravis?oldid=681043705 Contributors: General Wesc, Vicki
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14.2 Images
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utors: ? Original artist: ?
• File:Gray1178.png Source: https://upload.wikimedia.org/wikipedia/commons/8/80/Gray1178.png License: Public domain Contributors:
Henry Gray (1918) Anatomy of the Human Body (See “Book” section below)
Original artist: Henry Vandyke Carter
• File:Myasthenia_gravis_ptosis_reversal.jpg Source: https://upload.wikimedia.org/wikipedia/commons/5/57/Myasthenia_gravis_
ptosis_reversal.jpg License: CC BY 2.0 Contributors: Rare association of thymoma, myasthenia gravis and sarcoidosis : a case report.
Journal of Medical Case Reports. 2008;2:245. doi:10.1186/1752-1947-2-245 Original artist: Mohankumar Kurukumbi, Roger L Weir,
Janaki Kalyanam, Mansoor Nasim, Annapurni Jayam-Trouth.
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• File:Tumor_Thymoma1.JPG Source: https://upload.wikimedia.org/wikipedia/commons/3/3f/Tumor_Thymoma1.JPG License: GFDL
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