myesthenia gravis

2. 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.

3.  MyastheniaMyasthenia (Greek – muscle(Greek – muscle
illness)illness)
 GravisGravis (Latin – “grave or(Latin – “grave or
serious”)serious”)
 First description in the 17First description in the 17thth
centurycentury
Sir Thomas WillisSir Thomas Willis
 ““a woman who spoke freely anda woman who spoke freely and
readily enough for a while, butreadily enough for a while, but
after a long period of speech wasafter a long period of speech was
not able to speak a word for onenot able to speak a word for one
or two hours”or two hours”

4.  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.
4

5. 5
 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.

6. 6
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.

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

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

9.  Penicillamine users (rheumatoid arthritis)
 Enlarged Thymus or thymoma

10. 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 earlier
ocular 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.

13.  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 +/- limb~75% develop head/neck +/- limb
weakness.weakness.
 ~67% reach maximum MG~67% reach maximum MG
severity.severity.
 ~20% experience severe~20% experience severe
exacerbation/MG crisis.exacerbation/MG crisis.

14.  May be exacerbated by:
 Infection
 Stress
 Fever
 Adverse reaction to medicines e.g aminoglycosides,
tetracyclines, B-blockers, quinidine, procainamide,
lidocaine.

15.  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.

16.  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…

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

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

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

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

21. 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.

22. BEFORE. AFTER.

23.  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.

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

25.  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.

26.  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)

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

28.  Muscle biopsy
This is only done if the diagnosis is in doubt and a
muscular condition is suspected.
 Pulmonary function tests.
spirometry for breathing adequacy
FVC 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.

29.  Acetylcholinesterase inhibitors.
 Corticosteroids.
 Immunosuppressant.
 Plasmapheresis.
 Thymectomy.

30. 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.

31. 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

32. 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.

34.  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.

35.  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.

36.  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.

37.  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.

38.  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.

39.  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.

40.  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.