Mabalot,Mark Johann O.

BS BIOLOGY 4a

Catolico, Karen Faye April 25 2017

Trajera,Francis

Benemerito, Nemorie

Case Study: Animal Physiology Lecture

Myasthenia Gravis

Introduction

Myasthenia gravis is a chronic autoimmune neuromuscular disease characterized by

varying degrees of weakness of the skeletal (voluntary) muscles of the body. The name

myasthenia gravis, which is Latin and Greek in origin, literally means "grave muscle weakness."

With current therapies, however, most cases of myasthenia gravis are not as "grave" as the name

implies. In fact, most individuals with myasthenia gravis have a normal life expectancy (Tzartos

et al., 1998).

The hallmark of myasthenia gravis is muscle weakness that increases during periods of

activity and improves after periods of rest. 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 muscles that control breathing and neck and limb movements may

also be affected.

Description

Myasthenia gravis (MG) is a long-term neuromuscular disease that leads to varying

degrees of skeletal muscle weakness. 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. Onset can be sudden. Those affected often have a large thymus gland or develop a

thymoma (Archives of Neurology, 2012).

Myasthenia gravis is an autoimmune disease which results from antibodies that block or destroy

nicotinic acetylcholine receptors at the junction between the nerve and muscle. This prevents

nerve impulses from triggering muscle contractions.Rarely, an inherited genetic defect in the

neuromuscular junction results in a similar condition known as congenital myasthenia.Babies of

mothers with myasthenia may have symptoms during their first few months of life, known as

neonatal myasthenia. Diagnosis can be supported by blood tests for specific antibodies, the

edrophonium test, or nerve conduction studies.

Myasthenia gravis is generally treated with medications known as acetylcholinesterase

inhibitors such as neostigmine and pyridostigmine. Immunosuppressants, such as prednisone or

azathioprine, may also be used. The surgical removal of the thymus gland may improve

symptoms in certain cases. Plasmapheresis and high dose intravenous immunoglobulin may be

used during sudden flares of the condition. If the breathing muscles become significantly weak,

mechanical ventilation may be required.

Case History

Case #1:

A 67-year-old man, complaining of double vision, was found to have bilateral ptosis, covering

most of the pupil on the right side and partially obscuring that on the left. The ptosis was worse

in the evening and almost absent in the morning. He admitted to tiredness in the arms and legs on

exercise, which recovered with resting. A clinical diagnosis of ocular myasthenia gravis was

made. His Tensions test was positive but electromyography was inconclusive. His serum
contained antibodies to thyroid microsomes (positive at 1/1600) and to acetylcholine receptors.

The patient improved on treatment with pyridostigmine.

Case #2:

A 21-year-old woman was referred to a neurology clinic with a 1-month history of double

vision, difficulty swallowing and weakness in her upper arms. These symptoms were mild or

absent in the morning and tended to worsen through the day. When she was seen towards the end

of an afternoon neurology clinic she was found to have a bilateral ptosis and disconjugate eye

movements that could not be ascribed to any individual cranial nerve lesion. Her upper limb

power was initially normal but deteriorated with repeated testing. An intravenous injection of

edrophonium, a short-acting cholinesterase inhibitor, completely abolished the neurological signs

but her eye movements deteriorated again 30min after the injection. A clinical diagnosis was

made of myasthenia gravis. Subsequent blood testing showed the presence of a high level of

antibodies against the acetylcholine receptor.

She was treated with oral cholinesterase inhibitors with some improvement. However, 1

month later she deteriorated and corticosteroids were introduced with no improvement. A

computed tomography scan of her thorax showed no evidence of a thymoma but she was

nevertheless referred to a thoracic surgeon for thymectomy as this can sometimes induce

remission in myasthenia even in the absence of a thymoma. A small thymic remnant was

removed and she recovered uneventfully and was able to withdraw from all medication without

deterioration in her symptoms. Acetylcholine receptor antibody levels fell but remained

detectable. One year later, she became pregnant and after an uneventful 41-week pregnancy she

delivered a 4-kg male infant. There were immediate concerns about the baby who failed to make

adequate respiratory efforts and who appeared limp and hypotonic. The baby was intubated and
ventilated on the neonatal intensive care unit. In the light of the mother's history, a provisional

diagnosis of neonatal myasthenia gravis was made, although care was taken to exclude other

causes of neonatal respiratory insufficiency such as maternal analgesia with pethidine,

hypoglycaemia and sepsis. A cranial ultrasound showed no evidence of bleeding or other

pathology. Subsequent testing of a blood sample taken from the umbilical cord showed low

levels of acetylcholine receptor antibody. The baby needed ventilation and feeding via a

nasogastric tube for 3 days at which time the ventilation was successfully withdrawn. There were

some initial feeding problems due to difficulty sucking and swallowing but these resolved over

the next 48h. The child's subsequent development has been entirely normal. The mother also

remains well.

Etiology and Epidemiology

Myasthenia Gravis (MG) is a neuromuscular disorder that causes muscle weakness. The

name Myasthenia gravis came from a Latin and Greek words which literally means grave

muscle weakness. It usually affects voluntary muscles or muscles that are can be controlled

consciously. It is characterized by weakness of muscles such as ocular, neck, limbs, bulbar and

respiratory. It is not a permanent weakness of muscle but it is fluctuating without losing the

reflexes of sensation or other neurologic function. The symptoms worsen temporarily and

improve with a rest. MG is classified as an autoimmune disease which means that the bodys

immune system attacks the connection between the nerve and muscle mistakenly. The weakness

of the muscle is the result when the muscle cells cannot respond properly to the nerve impulses

that signals them to contract (Thanvi and Lo, 2008).

Myasthenia gravis affects approximately 100 patients per million people (Jacob et al.,

2009). According to Yu et al., 1989 women are more affected twice than men but it has no
significant gender difference in incidence exists before puberty or after the age of forty. This

deases affects all age groups and peaks in ages twenty and thirty in women while fifty and sixty

years old in men (Jacob et al., 2009). The first case reported of MG is a native American Chief

Opechancanough who died in 1664. It was described as an excessive fatigue with macerated

flesh. The vigority has been lost their tone and elasticity. The person is not able to open his

eyelids since he felt that it is so heavy and he cannot see unless his eyelids were lifted up by his

attendants. Furthermore he cannot walk due to weakness of his leg muscles (Conti, 2006).

Myasthenia gravis is considered as a serious disease but can be treated. The fatigability of

the voluntary muscles are caused by autoantibodies against the nicotinic acetylcholine receptor

(AChR) on the postsynaptic membrane at the muscular junction (Tzartos et al., 1998). The

antibodies are produced by bodys own immune system to protect it from foreign organisms but

in Myasthenia gravis, these antibodies mistakenly attack it.

This disease is caused by a defect in the transmission of nerve impulses to muscles. It

takes place if the normal communication between the nerve and muscle is interrupted at the

neuromuscular junction. Neuromuscular junction is the place where nerve cells connect with the

muscles they innervate. Acetylcholine is one of the neurotransmitter in our brain cells that is used

by the nervous system to communicate with other brain cells. It is found in the interface between

the presynaptic nerve terminal and postsynaptic muscle membrane. Acetylcholine are released by

nerve endings and it travels from neuromuscular junction and binds to acetylcholine receptors

which are activated and generate a muscle contraction (Thanvi and Lo, 2008).

The symptoms of MG includes problems walking upstairs or lifting objects, paralysis of

the face, difficulty in talking and breathing due to muscle weakness, trouble in swallowing and
chewing, having a hoarse voice, drooping of eyelids, fatigue, and double vision (Herndon, 2016).

This autoimmune disease is also characterized by:

Specific muscle weakness rather than generalized weakness

Extraocular muscle weakness or ptosis
Bulbar muscle weakness
Limb weakness in proximal parts of the body
Severity of weakness is common in the morning and worsens as the day progress
Weakness starts from ocular and spreads to facial to bulbar muscles and then to

truncal and limb muscles (Shah et al., 2016).

Myasthenia gravis are divided into five main classes and several subclasses by the

Myasthenia Gravis Foundation of America (MFGA) (Jaretzky, 2000).

Class I is characterized by ocular muscle weakness; inability to close the eyes; other

muscle strength are normal

Class II shows weakness on other muscles of the eyes; eye muscle weakness can be in

any severity
Class IIa is characterized by lesser involvement of oropharyngeal muscles and the limbs,

axial muscles or both are predominantly affected

Class IIb : the oropharyngeal, respiratory muscles or both are predominantly affected;

lesser involvement of limb and axial muscles

Class III MG shows moderate weakness of other ocular muscles and can be at any

severity
Class IIIa: Affecting limb and axial muscles; involvement of oropharyngeal muscles
Class IIIb is characterized by affected oropharyngeal and respiratory muscles; lesser or

equal involvement of limb and axial muscles

Class IV shows severe weakness of muscles other than ocular and can be at any severity
Class IVa: Predominantly affecting limb, axial muscles or both; lesser involvement of

oropharyngeal muscles
 Class IVb is characterized by predominantly affected oropharyngeal, respiratory or both;

lesser or equal involvement of limb, axial muscles or both; feeding of a patient is done

through tube without intubation

Class V: Feeding can be done with the use of intubationwith or without medical

ventilation

The division of Myasthenia gravis symptoms is designed to identify subgroups of patient

who share the same severity of disease which may indicate different responses to therapy (Trouth

et al., 2012).

Several factors could trigger and worsen the disease. The following factors are: Bright

sunlight, surgery, immunization, emotional stress, menstruation, intercurrent disease such as viral

infection and medications (aminoglycosides, ciprofloxacin, chloroquine, procaine, lithium

phenytoin, beta-blockers, procainamide and statins) (Shah et al., 2016).

Diagnosis

Many disorders can cause weakness of muscles, Myasthenia Gravis is one of them. The

diagnosis of Myasthenia Gravis should be made by a neurologist. According to the study of

American Academy of Neurology (2016) the evaluation may include medical and neurologic

evaluation, Blood tests to check for antibodies, Blood tests or other studies to rule out other

causes of weakness, imaging scans, electrical tests of nerve and muscle function

(electromyography and nerve conduction studies), and Ice pack test to improve strength of the

eyelid.

A provisional diagnosis may be made using the edrophonium test or Tonsilon test

(Matthew, 2004), a drug called Tonsilon or a dummy medicine (inactive placebo) is given during

this test. The health care provider gives the appropriate one through one of the patient's veins, the

action of Tonsilon drug include inhibits acetylcholinesterase, prolongs presence of

neurotransmitter, acetylcholine, in the neuromascular junction, and results in enhanced muscle

strength. The patient is MG positive if most of myasthenic muscles respond in 30 to 45 seconds

after injection, improvement in strength that may persist for up to 5 minutes, and requires

objective improvement in muscle strength (Archives of Neurology, 2012) patient with

Myasthenia gravis frequently have other disease that have presumed or known immunological

cause such as thyroid disease, rheumatoid arthritis, and vitamin B12 deficiency (Howard, 2008).

Treatment

Modern treatment of myasthenia gravis is highly effective. According to the research of

Thanvi (2004) the following treatment modalities are available: acetylcholinesterase inhibitors -

these drugs act by inhibiting acetylcholinesterase and thus increase availability of the

acetylcholine to act on the ACh receptors. They are usually the initial drugs used in the treatment

of myasthenia gravis and may the only drug required to treat mild disease, corticosteroids,

immunosuppressants, plasmapheresis, intravenous immunogobulins, and thymectomy. The

treatment of myasthenia gravis can be considered to involve three steps: (1) initial treatment

usually involves use of the acetylcholinesterase inhibitors. However, these drugs are usually not

adequate to control disease on their own and an additional therapy is mostly needed. (2) Often an

immune directed treatment is added, beginning with either thymectomy or high dose

corticosteroids. (3) In the long term, steroid-sparing medications are usually added to facilitate

the tapering phase. Short term therapies, intravenous immunoglobulin or plasmapheresis, may be

effective in the early stages of treatment, before thymectomy, or later during an exacerbation

(Thanvi, 2004).

References:

Archives of Neurology.2012. MYASTHENIA GRAVIS: DIAGNOSTIC TESTS. Retrieved from

http://neuromuscular.wustl.edu/mtime/mgdx.html
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p://patients.aan.com/globals/axon/assets/9583.pdf

Conti-Fine B. M., M. Milani, and H. J. Kaminski.2006. Myasthenia gravis: past, present, and
future, Journal of Clinical Investigation, vol. 116, no. 11, pp. 28432854

Herndon J. 2016. Myasthenia gravis. Healthline Media. University of Illinois-Chicago, College

of Medicine. Retrieved from www.healthline.com/health/myasthenia-gravis

Howard, J. F. 2008. Myasthenia Gravis: A Manual for Health Care Provider. Myasthenia Gravis
Foundation of America. ISBN: 0981888305

Jacob S., S. Viegas, D. Lashley & D. H. Jones. 2009. Myasthenia gravis and other neuromuscular
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Jaretzki, A. R. J. Barohn, R. M. Ernstoff et al., Myasthenia gravis: recommendations for

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Matthew, M. N. & Donald S. B. 2004. Myasthenia Gravis: Diagnosis. Department of Medicine,

Division of Neurology, Duke University Medical Center, Durham, North Carolina.
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Shah, A., F. Fana & N. Lorenzo. 2016. Myasthenia gravis. Medscape Drugs &
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Trouth A. J., A. Dabi, n. Solieman, M. Kurukumbi & J. Kalyanam. 2012. Review Article
Myasthenia Gravis: A Review. Hindawi Publishing Corporation. Autoimmune Diseases.
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Thanvi, B. R. 2004. Update on Myasthenia Gravis. Department of Integrated Medicine, Leicester

Royal Infirmary, University Hospitals of Leicester. DOI:
10.1136/pgmj.2004.018903

Thanvi, B. R. & T. C. Lo. 2008. Update on Myasthenia Gravis. doi: 10.1136/pgmj.2004.018903.

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YuYL, Hawkins BR, Wong VCN, et al. The Hong Kong Myasthenia Gravis Data Bank. J Hong
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