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M YA S T H E N I A G R A V I S

NA S HAO
CASE
• Case information: Mr.Wang 39 years old

• Chief complaint: repeated ptosis of both upper eyelid for 9 years,

powerlessness of four limbs for 8 year, acute exacerbation for 5 days

• Main history: 9 years before, the patient feel ptosis of both upper eyelid,

the symptoms was mild in the morning and severe in the evening, the

symptom was aggravated within 9 years. 8 year ago, he felt weakness of

the four limbs, and dysphagia, barylalia, he could walk and write in the

morning, but the symptom was severe in the evening, and he felt too

weakness to accomplish his work. 5 days ago, the symptoms exacerbated

after a cough, he felt hard to breath, oxygen saturation decreased to 85%.


DEFINITION
• Myasthenia gravis (MG) is caused by a defect of neuromuscular transmission owing to

antibody-mediated attack on nicotinic acetylcholine receptor (nAChR) or muscle-specific

tyrosine kinase (MuSK) at neuromuscular junctions. It is characterized by fluctuating weakness

that is improved by inhibitors of cholinesterase.

• Belong to the neuromuscular junction disease (NMJ).


PATHOGENESIS
• In MG, antibodies are most often directed against the

postsynaptic nAChR.

• These antibodies directly block the binding of

acetylcholine and lead to a complement-mediated attack

and internalization of receptors.

• The result is distortion of the endplate with loss of the

normal post-junctional folds and a reduction in the

concentration of the receptors.


PATHOGENESIS
• MuSK plays a role in clustering of nAChRs at the NMJ,

thus, even though acethlcholine is realeased normally

from the presynaptic bouton, its effect at the endplate

in MG is limited because of the reduced density of

nAChRs.
SYMPTOMS
The characteristics of MG:

1. The fluctuating nature of myasthenic weakness is unlike any other disease

2. The distribution of weakness

3. The clinical response to cholinergic drugs


SYMPTOMS
The characteristics of MG:

1. The fluctuating nature of myasthenic weakness is unlike any other disease;

2. The distribution of weakness

3. The clinical response to cholinergic drugs


SYMPTOMS
The fluctuating nature of myasthenic weakness is unlike any other disease.

The weakness varies in the course of a single day, sometimes within minutes,

and it varies form day to day or over longer periods.

 symptoms are typically worse with sustained activity or toward the end of the

day.
SYMPTOMS
The characteristics of MG:

1. The fluctuating nature of myasthenic weakness is unlike any other disease;

2. The distribution of weakness

3. The clinical response to cholinergic drugs


SYMPTOMS
• The specific symptoms depend on the distribution of weakness.

1. Oscular involvement is most common, manifesting as ptosis and diplopia.

2. Bulbar muscle weakness is next most frequent and manifests as dysarthria or dysphagia.

3. Limb and neck weakness is also common, but in conjunction with cranial weakness, almost

never are the limbs affected alone.

 Most patients with MG have generalized disease, but as many as 15% may have involvement

restricted to the ocular muscles.


MYASTHENIC CRISIS
• Crisis is most likely to occur in patients with oropharyngeal or respiratory muscle

weakness.

• A medical emergency.

• Seems to be provoked by respiratory infection in many patients or by surgical

procedures, including thymectomy, emotional stress, systemic illness, cough and so on.
SYMPTOMS
The characteristics of MG:

1. The fluctuating nature of myasthenic weakness is unlike any other disease;

2. The distribution of weakness

3. The clinical response to cholinergic drugs


SYMPTOMS
• The clinical response to cholinergic drugs occurs so uniformly that it has

become part of the definition.

• It is difficult to demonstrate in patients with purely ocular myasthenia.


DIAGNOSTIC EVALUATION
• Repetitive nerve stimulation

• Clinical response to cholinergic drugs

• Antibodies to AChR

• Radiographs of the chest


DIAGNOSTIC EVALUATION
• Repetitive nerve stimulation

• Clinical response to cholinergic drugs

• Antibodies to AChR

• Radiographs of the chest


• Progressive decrement in the amplitude of muscle action potentials evoked by repetitive

nerve stimulation at 3 to 5 Hz.

• In generalized MG, the decremental response can be demonstrated in about 90% of

patients.

• Reduced to about 20% of normal.


DIAGNOSTIC EVALUATION
• Repetitive nerve stimulation

• Clinical response to cholinergic drugs

• Antibodies to AChR

• Radiographs of the chest


• The dramatic improvement that follows the injection of

neostigmine bromide (Prostigmin) or edrophonium

(Tensilon) makes the administration of these drugs

pertinent.

• If no such response occurs, the diagnosis of MG is

uncertain.
• In the neostigmine test, 1.5 to 2 mg of the drug and atropine sulfate, 0.4mg, are

given intramuscularly. Objective improvement in strength is recorded at 20-

minute intervals up to 2 hours.

• Edrophonium is given intravenously in a dose of 1 to 10 mg.The initial dose is

2mg followed in 30 seconds, if necessary, by an additional 2 mg and in another

15 to 30 seconds by 5mg to a maximum of 10mg. Most responses are seen

within doses less than 5.0mg.


DIAGNOSTIC EVALUATION
• Repetitive nerve stimulation

• Clinical response to cholinergic drugs

• Antibodies to AChR

• Radiographs of the chest


• Antibodies to AChR are found in 85% to 90% of patients of all ages with generalized MG and

~40% of patients with ocular MG.

• Antibodies may not be detected in patients with strictly ocular disease, in some patients in

remission (or after thymectomy), or even in some patients with severe symptoms.

• The titer does not match the severity of symptoms, for example, patients in complete clinical

remission may have high titers.


DIAGNOSTIC EVALUATION
• Repetitive nerve stimulation

• Clinical response to cholinergic drugs

• Antibodies to AChR

• Radiographs of the chest


• Many MG patients accompanies with thymomas.
• Antibodies to myofibrillar proteins (titin, yosin, actin, actomuosin) are found in 85% of patients
with thymoma and may be the first evidence of thymoma in some cases.
• Radiographs of the chest provide evidence of thymoma in about 15% of patients, especially in
those older than 40 years.
• CT of the mediastinum demonstrates all but microscopic thymomas.
• MRI is not more sensitive than CT.
DIAGNOSIS
• The diagnosis of MG is primarily clinical, and support for the diagnosis may be obtained from
various tests.

• The diagnosis of MG is supported by the finding of high titers of antibodies to AChR, byt a
normal titer does not exclude the diagnosis.

• Responses to repetitive stimulation are very important.

• If a thymoma is present, the diagnosis of MG is likely.


DIFFERENTIAL DIAGNOSIS
• ALS (amyotrophic lateral sclerosis)

• BSP (blepharosoasm)

• LEMS (Lambert-Eaton syndrome)


ALS
BSP
LEMS
• Is an uncommon condition that is usually associated with an underlying small cell lung
carcinoma.
• It is caused by antibodies which reduce the release of acetylcholine in presynaptic.
• In contrast to MG, bulbar and ocular symptoms are rare, but autonomic complaints are
common.
• A decremental response on slow repetitive nerve stimulation (3-5Hz).
• An incremental response on fast repetitive nerve stimulation (10 Hz).
TREATMENT

• Anti-acetylcholinesterase drugs: such as pyridostigmine

• Immune-modulating therapy

• Immunosuppressive therapy

• Plasmapheresis and intravenous immunoglobulin (IVIg)

• Thymectomy
TREATMENT

• Anti-acetylcholinesterase drugs: such as pyridostigmine

• Immune-modulating therapy

• Immunosuppressive therapy

• Plasmapheresis and intravenous immunoglobulin (IVIg)

• Thymectomy
• pyridostigmine is the most common used

• Side effect: abdominal cramps and diarrhea

• The usual starting dose pf pyridostigmine is 60mg given orally every 4 hours

while the patient is awake.

• Cholinergic drugs do not return function to normal, and the risk of crisis

persists because the disease is nor cured.


TREATMENT

• Anti-acetylcholinesterase drugs: such as pyridostigmine

• Immune-modulating therapy

• Immunosuppressive therapy

• Plasmapheresis and intravenous immunoglobulin (IVIg)

• Thymectomy
• Prednisone therapy

• 60mg to 100 mg daily, to achieve a response within a few days or weeks

• An equally satisfactory response can be seen with a lower dosage, but it takes longer.
TREATMENT

• Anti-acetylcholinesterase drugs: such as pyridostigmine

• Immune-modulating therapy

• Immunosuppressive therapy

• Plasmapheresis and intravenous immunoglobulin (IVIg)

• Thymectomy
TREATMENT

• Anti-acetylcholinesterase drugs: such as pyridostigmine

• Immune-modulating therapy

• Immunosuppressive therapy

• Plasmapheresis and intravenous immunoglobulin (IVIg)

• Thymectomy
• IVIG therapy is usually given in

five daily doses to a total of 2g/kg

(or 0.4g/kg*d) body weight.

• Plasmapheresis can given for

several times (125mg/kg in total).


TREATMENT

• Anti-acetylcholinesterase drugs: such as pyridostigmine

• Immune-modulating therapy

• Immunosuppressive therapy

• Plasmapheresis and intravenous immunoglobulin (IVIg)

• Thymectomy
• Thymectomy is recommended for most patients

with generalized MG.

• Although it is safe, thymectomy is a major

operation and is not usually recommend for

patients with ocular myasthenia unless there is a

thymoma.
Thank you!