1. DR. ANITA AGGARWAL
SENIOR CONSULTANT
OB/GYN

2. History
 31 yrs old lady first reported in feb 2012 with
history of amenorrhea for 2mths and myasthenia
gravis for 9 yrs.
 Personal History: Resident of Assam. Second in
birth order. Has 2 sisters 1 brother. Working as CA.
Married for 11mths.
 Family History: Mother Hypertensive, father died
of liver cirrohsis. H/o Downs Syndrome both sides.
 Menstrual history: cycle 3-5days/28-30days.
LMP-16.12.2011

3. Past History
In 2003- Pt. suddenly developed ptosis and diplopia she
was shown to opthalmologist and given conservative
treatment.
2007- she started having muscle weakness, knee
instability ,inability to climb stairs. Then Neurologist
suggested - Neostigmine test,Ach R antibodies. Both
were positive. CT Thorax ruled out Thymoma.Put on
Distinone 60mg 4hrly. Improved and started working
normally.

4. Contd--
 In 2008- she was shown in Holy Family Hospital and
advised Thymectomy. Surgery was done and she
improved a lot.her dose of Distinone was reduced to
120mg daily.
 H/P-Thymic Follicular Hyperplasia
 In-2011-Ptosis in left eye increased so Distinone
increased to 60 mg 8 hrly.She continued this dose till
date.

5. Ante Natal Period.
 She got married in 2011. Conceived after 6 months
spontaneously.She continued on Distinone through
out pregnancy.
 First trimester-has excessive nausea and vomitting and
weakness. She stopped going to office and continued
resting at home.
 Second trimester- uneventful.wt. gain, BP was
optimum

6. Contd-
 In late sec. trimester -she started having oedema
lowerlimb
 Third trimester-IUGR noted. Put on amino
acids, antioxidants dietary changes and adv. rest.Serial
USG with doppler studies done to monitor growth.
 Investigations-Hb12gm%.Normal TFT,blood
sugar, urine,LFT(low A:G ratio).Bl.group-O neg ICT
neg.Viral markers – NR
 GPE & Systemic exam- unremarkable.

7. Delivery Details
 In lieu of IUGR, decreased foetal movements IOL
planned at 37.4wks. Induction started with Cerviprime
and augmented with Syntocinon but she had uterine
inertia and MSL so LSCS was done under spinal
anesthesia.She delivered a female baby weighing 2.2
kg. PO period was uneventful.Mother and baby were
discharged on 4th PO day. Lactation was not well
established. Mother & Baby are doing fine till date.

8. Myasthenia Gravis
. Myasthenia gravis is an autoimmune neuromuscular
disease characterized by weakness and fatigue of the
skeletal muscles of the face and extremities.
It affects people of both sexes and all ages.
 Female patients are affected twice more commonly
than male patients.
 Myasthenia gravis usually strikes in women in their
third decade of life.
 First clinical discription by- Thomas Willis in 1672

9. Epidemiology
 20 cases of generalized myasthenia gravis per 100,000
persons in the United States.
 Worldwide incidence is recorded as ranging from 20-100
per million, with the higher prevalence observed in those
nations with greater access to modernized diagnostic
resources and treatments, which correlates with increasing
longevity as well.
 The prevalence of myasthenia gravis in pregnancy is
estimated at 1 in 20,000.
 Transient neonatal myasthenia gravis occurs in
approximately 10-15% of births by mothers with
myasthenia gravis.

10. Etiology
Genetic studies have revealed a correlation between
early-onset myasthenia gravis, which affects women of
childbearing age, and the HLA-DR3 and B8 alleles.
The underlying pathology is the autoimmune
production of immunoglobulin G (IgG) antibodies
directed toward receptors on the postsynaptic
membrane at neuromuscular junctions (NMJs).

11. Neuromuscular junction

13. Pathophysiology
 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.

14. PATHOPHYSIOLOGY
In NMJ Ach is stored in vesicles---released
on Action potential.
Combines with AchRs at peak of POST
SYNAPTIC FOLDS.---binds with subunit
of Ach R ---Rapid influx of cations Na.
Depolarization at the end plate region of
muscle fiber---if sufficiently large –
MUSCLE CONTRACTION.
Ach is rapidly hydrolized by AchE present
in synaptic folds,diffuse away from
receptors

15.  In myasthenia gravis, autoantibodies, produced in the thymus
gland, directed at the acetylcholine receptor sites impair
transmission of impulses across the myoneural 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.

16. Contd-
Acetylcholine receptor (AChR) antibodies are detected
in approximately 85% of patients with generalized
myasthenia gravis, who are categorized as
seropositive.
 Anti-AChR antibodies reduce the number of available
AChR sites with which acetylcholine can interact to
induce local depolarization and subsequent muscle
fiber contraction.
Muscular weakness, the primary symptom in patients
with generalized myasthenia gravis, results.

17. Contd-
 Anti-AChR antibodies are not detected in patients with
seronegative myasthenia gravis
 The membrane protein muscle-specific tyrosine kinase
(MuSK) has been identified as the target of antibody attack
in approximately 40% of patients with seronegative
myasthenia gravis.[2]
 The MuSK protein functions at the cytoskeletal level of the
endplate by anchoring clusters of AChRs to the
postsynaptic neuromuscular junction membrane;
 therefore, autoimmune attack by anti-MuSK antibodies is
another mechanism through which interaction with
acetylcholine on the postsynaptic surface is reduced.[5]

18. Role of Thymus
 The autoimmune responses that inhibit acetylcholine
interaction on the postsynaptic membrane at
neuromuscular junctions (NMJs), resulting in the inability
of muscle fibers to contract, are often initiated and
maintained by the thymus
 . Abnormalities of the thymus are observed in nearly 85%
of patients with myasthenia gravis
 However, thymectomies lead to a reduction of symptoms
in nearly 85% of patients with myasthenia gravis without
identifiable thymus abnormalities.[6]
 Thus, evidence supports a correlation between thymus
activity and the incidence of myasthenia gravis.

19. History
Patients with myasthenia gravis present with
symptoms such as ptosis, diplopia, breathing and
swallowing difficulties, and weak limbs.
 Intermittent ptosis and diplopia are usually the initial
reported symptoms, presenting in about 85% of
patients with myasthenia gravis.
 Symptoms fluctuate in severity; they worsen with
exertion and are relieved with rest.
 Fatigue upon exertion is essential to making the
diagnosis.

20. Ptosis

21. Physical Examination
 Muscle strength should be assessed by having the
patient squeeze the examiner's hand repeatedly or
having the patient flex her arm against resistance.
 Facial weakness can be evaluated by asking the
patient to smile. A snarling expression may be evident
when the patient attempts to smile.
Diplopia and ptosis to be adressed.
 Deep tendon reflexes are preserved.

23. Investigations
Blood test- To detect antibodies
Electromyogram
Muscle Biopsy
Nerve Stimulation test
Edrophonium (Tensilon test )
Genetic tests
Imaging Scan CT or MRI (thymus)

24. Differential diagnosis
Lambert-Eaton myasthenic syndrome
Botulism
Hyperthyroidism
Neurasthenia
Intracranial mass lesion
Progressive external ophthalmoplegia
Drug-induced myasthenia gravis

25. Pregnancy and MG
Course of disease is variable
Pregnant patients face risks of
exacerbation, respiratory failure, adverse drug
response, crisis, and death.
Because the severity of symptoms, as well as maternal
mortality, is highest in the first 2 years following onset
of myasthenia gravis.
 It is advisable for women to delay pregnancy for at
least 2 years following diagnosis. Severity of symptoms
and risk of maternal mortality is lowest 7 years after
onset of the disease.

26. Contd-
Pregnant patients may have disease exerbation in
40%, remission in 30% or no change in 30%.
 Emotional distress,systemic illness and hot
temprature worsen the disease course.

27. Contd-
, Plauche found that exacerbations occurred in
approximately 41% of patients during pregnancy
 29.8% of patients postpartum.
 Approximately 4% of patients died because of
worsening of the disease or because of treatment
complications

28. Contd-
A study by Batocchi et al reported that the disease
worsened in 19% of patients.
 Approximately 60% of exacerbations occurred during
the first trimester, and approximately 28% post
partum.
 Premature delivery occurred in 7.4% of patients.
Cesarean delivery was performed in 30%.
 .The study concluded that no correlation exists
between myasthenia gravis severity before and during
pregnancy.[8]

29. Associated Disorders
 Systemic lupus erythematosus
 Pemphigus
 Hashimoto thyroiditis
 Scleroderma
 Dermatitis herpetiformis
 Autoimmune hemolytic anemia
 Polymyositis
 Sarcoidosis
 Thymic abnormalities are also associated with myasthenia
gravis. As many as 50-60% of patients have
lymphofollicular hyperplasia, and 10-20% have a thymoma

30. Complications
Some of the rare complications can occur.
Bone marrow suppression- suppression could be due
to megakaryocyte colony-forming unit suppressive
factor produced by autoimmune mechanisms.
Excerbation can be linked to the anxiety and
physiologic stress of pregnancy or due to medication.
Respiratory crises- This is one of most severe
complications. ~ 20% of patients experience that
require mechanical ventilation

31. Contd-
Infections- due to decreased immunity play a very
important role in the exacerbation of myasthenia
gravis during pregnancy.
Operative deliveries are common.
Preeclampsia- due to altered immune response.mag
sulf contraindicated (phenytoin)

32. Treatment
MG is a life long incurable disease.
Early detection is key to successful treatment.
Only symptoms can be reduced.
Aim of treatment is to prevent respiratory problems.

33. Drugs
Cholinestrase inhibitors- Pyrido- & Neostigmine to
improve Ms. strength
Corticosteroids- To reduce Ab production.
Immunosupressants- Azathiopurine,cyclosporins etc.
Plasmapheresis-To remove Ab.Effect last only for 2-3
wks.*
IVIG-0.4- 1mg/kg.Effect may last upto 3 mth

34. Anticholinesterase medications
 At least partial improvement
PYRIDOSTIGMINE :most widely used drug
 MOA within 15-30 min
 Lasts for 3-4 hrs
 30-60 mg tid
 Long acitng at night time
 Max dose 120 mg 3-6 hrs daytime
 Muscarnic side effects –diarrhea,abdominal cramps
.salivation –atropine,lopermaide .

35. immunosuppression
 Immediate improvement –IV Ig, plasmapheresis
 Intermediate – glucocorticoids,cyclosporine,tacrolimus
 Late – mycophenolate mofetil,tacrolimus
 Refractory cases -High dose cyclophosphamide reboots the
immune system –eliminates mature lymphocytes,but stem
cells are spared for the presence of aldehyde dehydrogenase
.

36. Glucocorticoids
 Single dose only
 15-25mg/d
 High doses –weakening
 Increase by 5 mg/d at 2-3 day interval
 50-60 mg/d for 1-3 months
 Alt day 1-3 months
 Zero dose when off symptoms

37. Mycophenolate mofetil
 1-1.5 g bid
 Inhibition of purine synthesis by denovo pathway
 Inhibits proliferation of lymphocytes
 Lack of adverse side effects
 Skin rashes,leucopenia.

38. Azathioprine
 50mg/d should be used
 2-3 mg/kg in children
 10 % develop idiosyncratic reactions
 Not to give allopurinol.
 Cyclosporine ,tacrolimus as adjunctives

39. Cholinergic crises
 Muscular weakness resulting from depolarization due to
overdosage of anticholinesterase agents used for MG
 Excess dose of anti Ach ase inhibitors
 Symptoms of OP poisoning
 Worsened by edrophonium test
 treatment -atropine

40. Surgery
Thymectomy-Thymectomy is recommended for most
young patients.
It improves the disease course and can improve
remission. Thymectomy is thought to remove an
antigen source and reduce an anti-AChR antibody
source.
 Thymectomy is performed when the disease is in
control.

41. Other Treatment considerations
 Monitoring patients for infection especially those on
steroids.
 Serial ultrasonography, nonstress tests, and
biophysical profiles should be used for pregnancies at
risk as per the usual obstetrical management protocol.
Many patients develop depression or comorbid
depressive episodes. Bupropion (Wellbutrin XL) can
be added
Potassium rich diet and adequate rest.

42. Precautions during LSCS
 Surgery is very stressful.
 Cesarean delivery is reserved only for necessary cases.
 Regional anesthesia is good for abdominal delivery.
 Epidural anesthesia could be used to decrease the
requirements of systemic medications and provide
anesthesia for outlet forceps.
 Amide-type local anesthetics are thought to be safe when
large doses of drugs are needed. The group recommended
general endotracheal anesthesia for cesarean delivery in
patients with respiratory problems.
 Depolarizing anesthetics must always be avoided.

43. Neonatal Effects Not only is the mother at risk, her baby also faces significant risks,
 Neonatal myasthenia gravis- are as high as 10-20%. Show espiratory
distress and inadequate suck.Most of the time it is transient and last for
app. 3wks. Due to transplacental transfer of antibodies.
 Prematurity- approximately 36.5%
 Severe malformation,- are pulmonary hypoplasia and arthrogryposis
 Death-
 Breastfeeding by the mother with myasthenia gravis is safe if she is
following a treatment course that utilizes pyridostigmine or
corticosteroids
 Mothers with myasthenia gravis being treated with
azathioprine, methotrexate, mycophenolate mofetil, or
cyclophosphamide should avoid breast feeding.

44. Pharmacologic precautions
 the following drugs should be avoided:
 Narcotics
 Tranquilizers
 Barbiturates
 Inhalation anesthetics (ie, halothane, trichloroethylene, ether)
 Magnesium and lithium salts
 Penicillamine
 Beta-adrenergic agents
 Aminoglycoside antibiotics
 Colistin
 Neomycin
 Tetracycline drugs
 Lincomycin
 Polymyxin
 Quinacrine
 Chloroquine. Quinolones.

45. Drugs to be avoided in MG
 Not all patients have adverse effects
Myasthenic
Weakness
exaggerated
Erythromycin
Azithromycin
Local
anaesthetic
xylocaine
Streptomycin
Ciprofloxacin
Levofloxacin
Ofloxacin
Gatifloxacin
Non depolarizing muscle
relaxants –
DTC,pancuronium
Propanol
Atenolol
Quininine
Magnesium
penicilliamine

46. Summary
Pregnancy-
 Counselling about the risks
 Review therapy
 consider thymectomy
Prenatal-
 Joint obs and Physician care
 Drugs
 Plasmapheresis in resistant cases
 Foetal survellance
 Avoid stress.

47. Summary contd.
Labour &Delivery-
 Minimize stress,
 Continue drugs,
 Steroid if reqd.regional analgesia,
 Assist ll-stage
 Avoid mgso4
Postnatal-
 Review drug
 neonatal monitoring,
 shorterm AchE to neonate.

48. CONFUCIUS--
 OUR GREATEST GLORY IS NOT IN
NEVER FALLING BUT IN RISING
EVERY TIME WE FALL.