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Myasthenia Gravis; Etiology, Pathophysiology, Symptoms, Management and

Complications

Article · June 2020

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 KASR ALAINY

Myasthenia Gravis;

Etiology, Pathophysiology, Symptoms, Management and

Complications

by

Ahmed Elgohary Mohamed Elgohary

First Year Undergraduate Student,

Kasr Alainy School of Medicine,

Cairo University
Myasthenia Gravis 1

Myasthenia Gravis;

Etiology, Pathophysiology, Symptoms, Management and

Complications

Abstract

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder, characterized

by weakness in the body’s skeletal muscles, in which the body’s own immune
system produces antibodies that blocks or breaks down the acetylcholine receptors
at the neuromuscular junction, which in turn blocks the muscle’s excitability by the
nerve. Usually, smooth and cardiac muscles are unaffected. This weakness is known
to worsen with activity and improve with rest. Ptosis, diplopia, impaired speaking,
difficulty in swallowing, problems in chewing, head drop and difficulties in walking
are the commonest presentations of this disease. Anticholinesterase medicine is not
only used to treat those patients but also to prove their diagnosis. Lifestyle changes
and medication could improve the patients’ symptoms. Plasmapheresis, artificial
ventilation and thymectomy are other treatment strategies in severe, complicated
cases. This study is aimed to emphasize the etiology and pathophysiology of this
disease as well as its symptoms and management. Also, a case study from the
literature will be included. Due to the ongoing COVID-19 pandemic, and due to the
fact that MG patients are treated by immunosuppressive therapy and could also have
respiratory muscles weakness, the possible effect the virus have on such patients will
be discussed.

Keywords: Myasthenia gravis, MG, COVID-19, hydroxychloroquine

Acknowledgments: I would like to express my sincere gratitude to my advisor Prof.

Elgohary Mohamed Elgohary Prof. of Neurosurgery, Kasr Alainy School of

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Myasthenia Gravis 2

Medicine for his continuous support during conducting this study, for his motivation,
patience and immense knowledge. His guidance helped me in all the time of research
and writing of this article. I could not have imagined having a better advisor and a
mentor for my study. I also thank my elder brother, Mohamed Elgohary, Clinical
Pharmacist at Children Cancer Hospital Egypt (57357), for the stimulating
discussions and for the sleepless nights we were working together to accomplish this
article.

Contact Information

Ahmed Elgohary Mohamed Elgohary,

First Year Undergraduate Student,
Kasr Alainy School of Medicine,
Cairo University,
Cairo,
Egypt.
Email: [email protected]
Mobile Number: (+20) 106 958 9900

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Myasthenia Gravis 3

Introduction & Aim of Work

Myasthenia gravis (MG) (In Greek, Mya: Muscle; astheneia: weakness. In Latin,
gravis: serious) 1, is an autoimmune neuromuscular disorder, characterized by
weakness in the body’s skeletal muscles, in which the body’s own immune system
produces antibodies that blocks or breaks down the acetylcholine receptors at the
neuromuscular junction, which in turn blocks the muscle’s excitability by the nerve.
This study is aimed to emphasize the etiology and pathophysiology of this disease
as well as its symptoms and management. Also, a case study from the literature will
be included. Due to the ongoing COVID-19 pandemic, and due to the fact that MG
patients are treated by immunosuppressive therapy and could also have respiratory
muscles weakness, the possible effect the virus have on such patients will be
discussed.

Go to…
1. Etiology
2. Pathophysiology
3. Symptoms
4. Diagnosis
5. Treatment
6. Complications
7. Case Study
8. Relation to COVID-19
Conclusion
References

1. Etiology

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Myasthenia Gravis 4

Most patients with MG are demonstrating blood samples including antibodies

against the acetylcholine receptors. Thus, it is thought that MG is caused by an
autoimmune reaction. It is believed that the thymus gland causes or maintains the
production of these antibodies because normally in the healthy adults the thymus
gland is small, yet in some MG patients, it is abnormally large or even have thymus
gland tumors (thymomas) (10-15%). Also, it is suspected that some microorganisms
trigger the autoimmune reaction.6,7,9 This disease usually occurs in women below 40
years and men above 60 years, but generally speaking, it can occur at any age. In
the United States, is estimated to affect between 0.5 and 20.4 cases/100,000
individuals.2,3

Another type of MG is “antibody-negative myasthenia gravis” is known, too. In this

type, antibodies are produced against another protein called lipoprotein-related
protein 4 rather than acetylcholine receptors, resulting in the same condition.6

2. Pathophysiology

As a result of the acetylcholine receptors blockage, very few acetylcholine (ACh)

molecules binds to their complementary receptors on the sarcolemma, thus very

Figure 1 18

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Myasthenia Gravis 5

few acetylcholine-gated ion channels open on the sarcolemma, causing insufficient

Na+ influx into the muscle fiber and inadequate end plate potentials to initiate the
opening of the voltage-gated sodium channels. As a result, muscle fiber
depolarization does not occur.5 This is illustrated in Figure 1.

3. Symptoms

Generally, MG causes weakness in any skeletal/voluntary muscle in the body.

Usually, smooth and cardiac muscles are unaffected. 9 This weakness is known to
9
worsen with activity and improve with rest. Although any voluntary muscle is
affected, some groups of muscles are affected greatly as 6:
1- Eye Muscles 6
The first clinical picture that occurs in more than 50% of MG patients involves eye
disorders as:
- Ptosis (drooping of eyelids), could be unilateral (Figure 2) or bilateral
- Diplopia (double vision), vertical or horizontal, which resolves when one eye
is closed

Figure 2 : Right unilateral ptosis 19

2- Face and Throat Muscles 6

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Myasthenia Gravis 6

The first clinical picture that occurs in more than almost 15% of MG patients:
- Impaired speaking causing soft or nasal speech, depending on which
muscles are weakened.
- Difficulty in swallowing.
- Problems in chewing. Muscles of mastication could weaken halfway
eating a meal.
- Facial expressions alteration (Figure 3) Figure 3 20

3- Neck and Limb Muscles 6

Weakness in the neck muscles may cause head drop
and weakness in leg muscles may cause difficulties in
walking.

Figure 4 21
4. Diagnosis 10

- Test the suspected patient’s response to MG treatment medicines. For example,

if the muscle weakness improves for a period of time when given an
anticholinesterase medicine it confirms MG.
- Blood tests for antibodies against acetylcholine receptors.
- Electromyogram (EMG) to detect abnormal electrical muscle activity.
- Genetic tests to determine if it is hereditary.
- Repetitive nerve stimulation test.
5. Treatment 9

Although there is no cure for myasthenia gravis, treatment may improve the
symptoms by either of the two means:

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Myasthenia Gravis 7

- Lifestyle Changes
 Avoid stress and heat exposure
 Resting as much as possible
 Use of eye patch to improve diplopia
- Medication
 Acetylcholineesterase (AChE) inhibitors as neostigmine (compete with
ACh for attachment to AChE at the neuromuscular junction) or
pyridostigmine
 Immunosuppressive drugs as prednisone, azathioprine, cyclosporine or
mycophenolate mofetil are used in case of severe symptoms with no
response to other drugs.
Other treatment strategies includes:
- A ventilator may be used during attacks of weakness of the breathing muscles
- Plasmapheresis may be used to stop the attacks of weakness of the breathing
muscles. This involves replacing the patient’s plasma containing the
antibodies against acetylcholine receptors, with antibodies-free donated
plasma or with other fluids.
- Thymectomy which could lead to permanent relief of symptoms or less need
for medicines.
- Lens prisms to improve vision due to eye problems.
- Physical therapy to maintain muscle strength.
6. Complications 6

Complications of MG are usually treatable, but some can be lethal as. Some of the
complications are:

- Myasthenic crisis, which is the failure in the breathing muscles

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Myasthenia Gravis 8

- Thymus gland tumors

- Other conditions like:
 Hypothyroidism or hyperthyroidism
 Other autoimmune diseases as lupus or rheumatoid arthritis

7. Case Study 11

Patient Presentation: Elsa, a 25 years-old female teacher, complains of double

vision and finds difficulty in talking after prolonged speaking.

History: episodes of double vision began 6 weeks ago. Her husband reported
fluctuating droopy eyelids, in the morning and evening, of four-week onset. She
described asthenia and generalized weakness when gardening. Symptoms worsens
at the end of the day.

Neurological Examination: bilateral ptosis, limitations in eye movements of both

eyes when looking to the right and to the left.

Musculoskeletal System Examination: waddling gait after 100 m

Treatment: the patient was initially treated symptomatically with pyridostigmine.

8. Relation to COVID-19

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Myasthenia Gravis 9

As MG patients are immunosuppressed and could have respiratory muscles

weakness, some theories are evolving that MG patients could have higher
susceptibility of contracting the COVID-19 or experience more severe
manifestations of COVID-19. However, MG patients should continue their
treatment and it is recommended complete their ongoing medications, unless
specifically discussed and approved by the healthcare expert. It is recommended that
immunosuppressed MG patients should practice social distancing measures more
strictly, and switch to telemedicine if possible, and to postpone the onset of the
immunosuppressive therapy till the end of the peak of the pandemic in their region,
if this is possible for the patient’s condition. If a MG patient has been infected with
COVID-19 and is experiencing severe symptoms that requires hospitalization, it
may be advisable to temporarily stopping the ongoing strong immunosuppressive
therapy (immune depleting ones), and especially if there is additional super added
infections or sepsis yet milder immune-suppressive agents like mycophenolate
12-16
should probably be continued. Also, MG cases due to chloroquine and
hydroxychloroquine have been reported, associated with recovery of symptoms and
the disappearance of the antibodies against acetylcholine receptors after stopping
chloroquine, suggesting a possible relation between the aforementioned drugs and
MG. Thus, introducing chloroquine and hydroxychloroquine to the COVID-19
treatment protocol in MG patients is contraindicated.17,18

Conclusion

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder, characterized

by weakness in the body’s skeletal muscles which worsens with activity and
improves with rest. Ptosis, diplopia are from the commonest symptoms of this
disease. Anticholinesterase medicine is used for both the treatment and diagnosis of
MG. MG patients are more susceptible to COVID-19 infection and could experience

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Myasthenia Gravis 10

more severe manifestations because they are immunosuppressed and could have
respiratory muscles weakness. Also, a possible relation between MG and
hydroxychloroquine has been found. For this reason, introducing this drug in the
treatment protocol of COVID-19 in MG patients is contraindicated.

Go to References
References

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