myasthenia gravis3

8/4/2019 Myasthenia gravis3

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Myasthenia gravis

Dr Frank I. Ojini

CMUL/LUTH


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Myasthenia gravis A disease xterized by abnormal muscular fatiguability or inability to

sustain a maintained or repeated contraction of striated muscle.

Has a tendency to remit and to relapse.

Occurs in all races.

< 40yrs F:M 7:3> 50yrs M:F 3:2

Usually begins in early adult life.

Closely related to thyrotoxicosis and the two can coexist.

Also an association with DM, rheumatoid arthritis, SLE, sarcoidosis.


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Aetiopathogenesis of MG MG is an autoimmune disease in which ABs against AChR cause

a disorder of conduction at the myoneural junction.

The circulating antibodies (mostly IgG) bind to the receptorsites in the post junctional memb of NMJs and cause damage in2 ways:

block the receptor sites

cross link the receptors and promote their rapid degradationthrough activation of complement.

The end result is the depletion of functional receptor sites.


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Aetiopathogenesis of MG II There is evidence that T lymphocytes (derived from the thymus)

play an important role in collaboration with B lymphocytes inproducing the anti-AChR antibodies.

Thymic abnormalities are often present in MG Thymic hyperplasia: 65% Thymoma: 10%

Recently it has been shown that T lymphocytes may play amore direct role by producing cytokines which directly damage

the receptors.

There is a genetic susceptibilily to MG shown by a significantassociation with HLA A1, B8 and DRW3 in Caucasians.


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Clinical features of MG The muscles most often affected are the ext ocular, bulbar,

neck, and shoulder girdle muscles in this descending order.

Ptosis of one or both upper lids is often the first symptom and isassociated with diplopia due to paralysis of one or more of theexternal ocular muscles.

These symptoms typically appear in the evenings when thepatient is tired and disappear after a nights rest.

Involvement of bulbar muscles: dysphagia and dysphonia.


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Clinical features of MG II In severe cases upper limb weakness may occur with

inability to lift the arms.

If only ocular muscles involved ocular MG

If other muscles affected generalized MG

Involvement of respiratory muscles can lead tobreathlessness and respiratory failure (myastheniccrisis).


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Diagnostic investigations Tensilon testinjection of the short-acting anticholinesterase, edrophonium

chloride (tensilon), causes improvement in muscle power within 30 secs, andpersisting for 2 to 3 minutes.

ice-pack test 2 mins of ice-pack application to the affected eye in MG

patients with ptosis

Detection of anti-AChR antibody in the serumpresent in 80% ofgeneralized MG and 55-60% of ocular MG (seropositive MG)Musk antibodiesAntibodies to muscle-specific tyrosine kinase (MuSK) found in 40% ofgeneralised seronegative MG

MuSK MG patients predominantly female with prominent bulbar, neck, shouldergirdle, and respiratory weakness

Electrophysiologic studiesto demonstrate muscle fatiguability by means ofrepetitive supramaximal stimulation.SFEMG:most sensitive diagnostic test. Demonstrates increased jitter.


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Other investigations Screening for other autoimmune disorders

especially thyroid disease.

CXR or CT scan of thorax to screen for thepresence of thymic hyperplasia or thymoma.


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Treatment of MG The standard treatment for MG in the past was

anticholinesterases (neostigmine and pyridostigmine) to inhibitacetylcholinesterase.

These drugs are still indicated for purely ocular MG

The current treatment for generalized MG is the use of steroids(prednisolone) with or without immunosuppressive drugs suchas azathioprine, cyclosporine, mycophenolate mofetil.

This is usually followed by thymectomy when significantimprovement has occurred.

Thymectomy is obligatory in all patients with thymicenlargement (because of the possibility of thymoma).


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Treatment of MG II Certain drugs-penicillamine, curare, aminoglycosides, quinine,

procainamide, and ca channel blockers, may cause amyasthenic-like syndrome or exacerbate weakness in MG pts.

Plasmapharesis (plasma exchange) is reserved for use in casesresisting other forms of treatment or in an emergency(myasthenic crisis) or when preparing a patient for thymectomy.

Recently intravenous immunoglobulins have become establishedin the treatment of myasthenic crisis and have been found to beas efficacious as plasmapharesis.


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Prognosis of MG Prognosis of MG is variable. Remissions sometimes

occur spontaneously.

Most often there is a relapse after an interval ofmonths or years.

Thymectomy with steroid therapy usually gives

normal life expectancy in most patients.

Prognosis is worse if the disease is associated with athymoma.


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Myasthenic crisis Defined as the need for assisted ventilation in a pt with MG

May be precipitated by respiratory infection or major surgery

Differentiating between myasthenic crisis and cholinergic crisis can bedifficult.

The most useful single test is to give IV edrophonium

If muscle power , then likely that the weakness is myasthenic and

requires more treatment.

If muscle power , the weakness is probably cholinergic and treatmentmust be reduced.

In severe cases, withdraw all drugs and start assisted respiration


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Treatment of myasthenic crisis Usually a temporary exacerbation that subsides in a few

days or wks

The therapeutic goal is to maintain vital functions and toavoid or treat infection until the patient spontaneouslyrecovers from the crisis.

The patient should be intubated and started on positivepressure artificial ventilation.

Plasmapharesis, and more recently intravenousimmunoglobulins, have been shown to shorten theduration of myasthenic crisis.

myasthenia gravis3

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