Myasthenia gravis also called GOLDFLAM disease is an autoimmune disorder,in which antibodies are directed against nicotinic acetylcholine receptors of neuromuscular junction which leads to reduce post synaptic response to acetylcholine resulting in significant muscle fatigue.

MyastheniaMyasthenia (Greek – muscle (Greek – muscle illness)illness)

Gravis Gravis (Latin – “grave or (Latin – “grave or serious”)serious”)

First description in the 17First description in the 17thth centurycenturySir Thomas WillisSir Thomas Willis

““a woman who spoke freely a woman who spoke freely and readily enough for a and readily enough for a while, but after a long period while, but after a long period of speech was not able to of speech was not able to speak a word for one or two speak a word for one or two hours”hours”

Normally, a chemical impulse precipitates the release of acetylcholine from vesicles on the nerve terminal at the myoneural junction. The acetylcholine continuously bind to the receptor sites on the motor end plate, for muscle contraction to sustain.

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In myasthenia gravis, auto antibodies, produced in the thymus gland, directed at the acetylcholine receptor sites impair transmission of impulses across the neuromuscular junction. Therefore, fewer receptors are available for stimulation, resulting in voluntary muscle weakness that escalates with continued activity. These antibodies are found in 80% to 90% of the cases. In patients who are antibody negative, it is believed that the offending antibody is directed at a portion of the receptor site rather than the whole complex.

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The thymus gland, a part of your immune system located in the upper chest beneath the breastbone, may trigger or maintain the production of antibodies that result in the muscle weakness common in myasthenia gravis.

Affect all age groups, peak incidence in women(20-30’s). In men (50-70’s). More common in women. Prevelance 1 in 7500.

• Diabetes Mellitus Type 1. Rheumatoid Arthritis. Lupus. Demyelinating CNS Disease. Other Auto-Immune Diseases.

Penicillamine users (rheumatoid arthritis)

Enlarged Thymus or thymoma

Fluctuating Muscle Weakness with fatigability increased by exertion,relieved by rest (hallmark sign)

Musle weakness spreads from ocular to facial to bulbar to trunkal to limb muscles.

Cranial muscles involved earlierocular muscles(ptosis,diplopia) in 50%.Bulbar(dysarthria,,dysphagia) in 15%.Face (difficulty in chewing , myasthenic snarl or

unusual smile)Neck flexors affected more than extensors.Limb girdle (weakness proximal > distal)Deep tendon Reflexes and sensations are normal.Inetrcostal muscles and diaphragm are also involved.

Initial SymptomsInitial Symptoms.. Eye muscle weakness.Eye muscle weakness.

75%75% Head/neck weaknessHead/neck weakness . .

15% 15% Limb weakness. 10%Limb weakness. 10%

Within first yearWithin first year.. ~75% develop head/neck +/- ~75% develop head/neck +/-

limb weakness.limb weakness. ~67% reach maximum MG ~67% reach maximum MG

severity.severity. ~20% experience severe ~20% experience severe

exacerbation/MG crisis.exacerbation/MG crisis.

May be exacerbated by: InfectionStressFeverAdverse reaction to medicines e.g aminoglycosides,

tetracyclines, B-blockers, quinidine, procainamide, lidocaine.

Defined as exacerbation of weakness usually withrespiratory failure, sufficient to endanger life. Expert management in an intensive care setting essential as is prompt treatment with IVIg or plasma pheresis to hasten recovery. Ventilatory support may also be required if failure of respiratory muscles occur.

Many mothers get worse 1st trimester and better 2nd and 3rd trimester.

Up to 10% of infants born to mothers with MG will have Transient Neonatal Myasthenia.Weak cry, poor muscle tone, difficulty breathing

etc…

LAMBERT –EATON SYNDROME NEURASTHENIA DRUG INDUCED MYASTHENIA BOTULISM DIPLOPIA FROM INTRACRANIAL MASS LESION HYPERTHYROIDISM PROGRESSSIVE EXTERNAL OPHTHALOMOPLAGIA

Aspiration. Respiratory Insufficiency. Respiratory infection. Acute exacerbation called Myasthenic Crisis.

Bed side (ice test ). Tensilon Test. Antibody Tests. Electrical Tests. Chest X-Ray. CT/MRI.

Ice application to the ( shut) affected eyelid for > 2mints improves ptosis > 2mm.

with resuscitation facilities and atropine at hand. A short acting anticholinesterase ,Edrophonium chloride10 mg, is injected IV. With in30secs , muscle power is increased, which persists for 2-3mints. This immediate improvement usually confirms the diagnosis.

BEFORE. AFTER.

Increase in 85%(50% in ocular confined MG.)

Antibody level does NOT correlate with disease severity.

Positive antibodies are diagnostic. If sero negative then look for MUSK(muscle specific tyrosinekinase antibodies present in 40% of pts with generalized MG.

• Repetitive Nerve Repetitive Nerve Stimulation (RNS).Stimulation (RNS).

•  Low frequency of (2-4Hz)repetitive stimulation produces rapid decrement in amplitude(>10-15%)of evoked motor responses.

Single Fiber EMG.Single Fiber EMG. Some patients may find this test uncomfortable. In a more precise version of this test, called single-fiber EMG, a single muscle fiber is tested. 

A chest X-ray is commonly performed, as it may point towards alternative diagnoses, such as Lambert-Eaton due to a lung tumor, and comorbidity (the presence of one or more disorders/diseases in addition to a primary disease/disorder)

CT /MRI of thorax to evaluate thymus(65% hyperplasia,10% thymomas) .may not be visible on plain X RAY.

Muscle biopsyThis is only done if the diagnosis is in doubt and a

muscular condition is suspected.  Pulmonary function tests. spirometry for breathing adequacyFVC to detect increasing muscle weakness.FVC of 15ml/kg is generally an indication for

intubation.Consider thyroid and other studies (e.g. ANA) for

associated autoimmune diseases.

Acetylcholinesterase inhibitors. Corticosteroids. Immunosuppressant. Plasmapheresis. Thymectomy.

maximizes activity of acetylcholine at receptors in NMJ’s.

Pyridostigmine (MESTINON) is given 30-120mg 6 hourly. Overdosage can cause muscirinic crisis controlled by propantheline 15mg 8 hourly or atropine or loperamide.

Corticosteroids are a mainstay of chronic immunosuppressive treatment. Begin Prednisone at low dose (15-25mg/day) increase by 5mg/day every 2-3 days, until marked clinical improvement or dose of 50-60 mg /day is reached. Maintain high dose for 1-3 months, then decrease to alternate day regimen

Immunosuppressive therapy

aims to reduce the production of the antibody. Azathioprine,cyclosporin,

cyclophosphamide,tacrolimus, mycophenolate mofetil , are alternative 3rd line agents, which may allow steroids to be reduced.

Done to remove putative antibodies from the circulation. .

In this procedure blood is removed from the body , the plasma is seperated from the cells are then suspended in saline (or a plasma substitue or donor’s plasma and the reconstituted solution is returned to the pt.

Used to bind circulating antibodies. 400mg/kg/day for 5 days.

Both of these treatments have relatively short lived benefits provides temporary boost to seriously ill-pts or before surgery or during myasthenic crisis.

Considered in antibody +ve pts under 45 years of age with symptoms outside the extraocular muscles.

may lead to improvement in upto 85 % of pts with thymoma.

Educate the pt regarding medicines , taking them on time.

Consequences of delaying administration and signs and symptoms of myasthenic and cholinergic crisis.

ACTIVITY Take frequent rests. Avoid sustained

activities.

DIET Plan the meal times with peak effects of

medication. Sitting upright during meals with neck slightly

flexed to facilitate swallowing, prefer soft foods to a pudding consistency.if

dysphagia occurs liquid should be thickened to prevent aspiration.

Suction should be available at home. Gastrostomy feeding may be necessary to ensure

adequate nutrition.

To prevent corneal ulcers, instruct the pt to tape the eyes closed for short intervals .

Regular use of artificial tears. Patch one eye can help with double visions.

Prognosis is variable ; remission sometimes occur spontaneously when disease is confined to eye muscles, the prognosis is excellent .rapid progression >5years after onset is uncommon.