This document summarizes diagnostic testing and treatment approaches for myasthenia gravis (MG). It describes that anti-striated muscle antibody tests are 90% sensitive for generalized MG and 50-70% for ocular MG. Positive results in those under 40 should prompt searching for thymoma. Half of seronegative MG patients may test positive for anti-MuSK or anti-LRP4 antibodies. Repetitive nerve stimulation and single-fiber electromyography can help diagnose MG. An edrophonium test involves injecting the drug to see if symptoms improve. Treatment includes pyridostigmine, steroids, azathioprine, thymectomy, plasmapheresis, and intravenous immunoglob

1. - Dr.Akif A.B

4. -100% specific
-90% sensitivity in Generalised Myasthenia
-50-70 % sensitivity in Ocular Myasthenia
-False positives are very rare and may be seen in Lambert eoton syndrome,
GVHD, Autoimmune liver disease, RA.

5. The anti–striated muscle (anti-SM) Ab refers to a class of antibodies
against components of skeletal muscle including titin, the ryanodine
receptor, myosin, and alpha-actin.
Anti-SM Ab is present in about 70–80% of patients with thymoma and MG
who are younger than 40 years
30% of adult patients with MG without thymoma
24% of patients with thymoma without MG.
Thus, a positive test result should prompt a search for thymoma in
patients younger than 40 years.
In individuals older than 40 years, anti-SM Ab can be present without
thymoma.
anti–striated muscle ANTIBODY

6. About half of the patients with negative results for anti-AChR Ab
(seronegative MG) may have positive test results for antibody to
muscle-specific kinase (MuSK)
-It is a Receptor tyrosine kinase that is essential for neuromuscular
junction development.
- Associated with more severe disease
- Doesn’t responds to Acetylchoilnesterase Inhibitors
Anti-lipoprotein-related protein 4 (LRP4) antibody
Lipoprotein-related protein 4 is present on the postsynaptic membrane

7. Rheumatoid factor and antinuclear antibodies (ANAs) is indicated to
rule out systemic lupus erythematosus (SLE) and rheumatoid arthritis
(RA).
Thyroid function tests are indicated to rule out associated Graves
disease or hyperthyroidism.
This is essential, especially in patients with ocular MG where the
concomitant hyperthyroidism is most frequent.
Other laboratory studies

8. On plain anteroposterior and
lateral views, radiography
may identify a thymoma as
an anterior mediastinal
mass.
A negative chest radiograph
does not rule out a smaller
thymoma, in which case a
chest computed tomography
(CT) scan is required.
Chest CT scan should be
obtained to identify or rule
out thymoma or thymic
enlargement in all cases of
MG, especially in elderly

9. It is essential to rule out mass lesions compressing the cranial
nerves in strictly ocular MG.
CT or preferably magnetic resonance imaging (MRI) of the brain
and orbit is indicated.

10. 1) Repetitive stimulation of a muscle at 2-3 Hz, also known
as repetitive nerve stimulation (RNS)
2) Single-fiber electromyography

11. Butterfly needle is placed in an accessible vein.
A 2 mg test dose is administered initially
If no response and no untoward effects are noted after 30 seconds
8 mg (0.8 mL) is injected in 2 mg increments every 10-15 seconds
If the patient has objective improvement (improvement in ptosis or
ophthalmoparesis) or a severe side effect, the test is aborted.
Sinus bradycardia due to excessive cholinergic stimulation of the heart is a
serious complication; consequently, an ampule of atropine(0.6mg) should
be available at the bedside or in the clinic room while the test is
performed.
False positive : amyotrophic lateral sclerosis, LEMS, botulism,
congenital myasthenic syndromes, and GBS

12. by cooling the tissues, and more specifically the skeletal muscle
fibres, the activity of the acetylcholinesterases are inhibited

13. Drugs for symptomatic therapy
Immunosuppressants and steroids

14. Drugs for
symptomatic therapy
- All subgroup responds to Acetyl cholinesterase inhibitors
-Pyridostigmine is the Drug of choice
-Neostigmine and Ambenonium chloride is also effective
-Myasthenia gravis with MUSK+ responds least to symptomatic therapy.
-Patients with mild diseases usually need no other therapy.

15. -Onset of action - 15-30min
-Duration of action = 3-4hrs
-Treatment generally begins with 30-60mg 3-4 times a day
-Maximum dose = 120mg , 3-4 times a day
-Overdose with anti cholinergics may cause increased weakness and SLUDGE.

16. Side effects of
Cholinesterase Inhibitors
-Increased salivation
-Lacrimation
-Urination
-Diarrhea
-Abdominal cramps(GIT)
-Emesis

17. -Prednisone or prednisolone
-Start at 15-20mg/day
-Slowly increase by 5mg every 2-3days
-Upto maximum of 60mg/day
-Continue for 3 months
-Put on alternate day therapy for 1-3months
-Slowly taper

18. -Aim : to prevent generalisation of Disease
-Low dose steroid is usually recommended for patients who have persistent
symptoms and have other factors involved like positive antibodies or
an enlarged Thymus.

19. -One of the most commonly used drug nowadays because of its
efficiency and fewer side effects
-Dose = 1-1.5g bd
-M.O.A = Inhibition of Purine synthesis by denovo pathway
-Lymphocytes have only denovo pathway, thus prevents proliferation
whereas other cells have salvage pathway as well and hence are not
affected.
-It doesn’t kill preexisting Lymphocytes and thus its action takes months
to act.
Life span of lymphocyte : few weeks to few months.
Side effects : GI symptoms and rarely leucopenia

20. INDICATIONS
Patients not responding to steroids
Patients not willing for steroids
Combination therapy is better and avoids
side effects
- Dose is 2-3mg/kg

21. -Inhibits purine synthesis and thus cell proliferation
-Active metabolite : 6-mercaptopurine
-Strong effect on T and B cells
-Thiopurine methyltransferase activity (metabolises azathioprine)
should be checked because its absence may increase toxicity of
Azathioprine
- 0.3% of people doesn’t have these enzyme
-Effect of Azathioprine takes months to appear, so till that time
alternate medicine should be used

22. -Most common - Nausea and vomitings
-Bone marrow suppression
-So counts should be monitored during therapy
-Very rarely Pancreatitis

23. -Methotrexate
-Tacrolimus
-Cyclosprine
-Rituximab : 375mg/m2 i.v in 4 weekly infusions or 1gm i.v 2 doses, 2
weeks apart
-Most guidelines recommend Mycophenolate mofetil for mild to
moderate Myasthenia Gravis

25. -Myasthenia Gravis patients with Thymoma benefit with Thymectomy.
-All Studies have shown that Thymectomy has a beneficial role in
patients with Myasthenia whether or not they have Thymoma
- It may lead to drug free remission as well
Not recommended
Patients with only ocular Myasthenia
With MUSK+ or LRP4 antibodies
All antibodies are negative
-There is less evidence that Thymectomy prevents Generalisation of Disease
-Thymectomy must be considered in patient with ocular Myasthenia only
if symptomatic therapy has failed or they are positive for Acetyl Choline
receptors and neurophysiological tests show possibility for Generalisation.
Thymectomy should be considered in negative antibodies patient if drug therapy
fails

27. Myasthenic crisis is a life-threatening condition
which is defined as weakness from acquired myasthenia
gravis that is severe enough to necessitate intubation or to
delay extubation following surgery.
The respiratory failure is due to weakness of respiratory
muscles.
Severe bulbar (oropharyngeal) muscle weakness
When this results in upper airway obstruction or severe
dysphagia with aspiration, intubation and mechanical
ventilation are necessary.
D/D : Cholinergic Crisis
Treatment : Immunoglobulins or Plasmapheresis

28. -Muscles stop responding to the high quantity of Ach due to
blockage of receptors, leading to flaccid paralysis, respiratory
failure and SLUDGE
- can be distinguished by Edrophonium test
- Treatment : Atropine + other supportive measures

32. -Plasma which contains the pathological antibodies are mechanically
separated from cells.
-A course of 5 cycles (3-4l/cycle) over period of 10-14 days
-Leads to significant improvement in symptoms
Indications
Myasthenia Crisis
To improve patients condition prior to surgery
(Thymectomy)

33. Indications
Myasthenia Crisis
To improve patients condition prior to surgery
(Thymectomy)
- 2gm/kg over 5 days i.e 400mg/kg/day

35. -Oral Prednisone or Pyridostigmine is safe during Pregnancy
-Azathioprine and cyclosporine is safe as well
-Methotrexate and Mycophenolate are contraindicated as they are
teratogenic
-Womens are advised to avoid pregnancy for upto 1 year after Rituximab
therapy
-Immunoglobulins and Plasmapheresis can be used in worsening Myasthenia
-Lactation should be continued
-Transient Myasthenia is seen in 15% of neonates due to transfer of IgG from
mother