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on 220 patients diagnosed with myasthenia gravis between 2003 and 2008 suggested that there is a similar incidence of anti-AChR antibody in Caucasians in the United States and African Americans but that there is a greater incidence of anti-MuSK antibodies in African Americans.
Edrophonium Improves ms strength. Inhibits AchE enzyme
Proximal (primarily leg) muscle weakness that improves with repeatedstimulation. Half of the time a\w small cell carcinoma of the lung.■ Autonomic symptoms (dry mouth, impotence) SYMPTOMS/EXAM of Botulism■ Onset 6–48 hours after ingestion of toxin or Clostridium botulinum spores■ Classic presentation = descending flaccid paralysis.■ Diplopia, dysarthria, and dysphagia occur early.■ Progresses to generalized weakness; ventilatory failure may occur■ May last for months■ In children, may present as constipation, feeding difficulty, andhypotonia.■ Other anticholinergic symptoms may be present (dry skin, dilated pupils,increased temperature).
These are two large studies.
can be linked to the anxiety and physiologic stress of pregnancy. Hypoventilation is a risk during pregnancy, because respiratory muscles are weakened from myasthenia gravis. Also, the lungs do not become fully inflated, because the diaphragm is elevated during pregnancy. Approximately 20% of patients experience respiratory crises that require mechanical ventilation. This is one of most severe complications.
Uterus is smooth muscle.Sec stage requiresskeltalms.
IVIG action starts only after 2-3 wks. Plasmapheresis effective ,expensive,life saving, can be done during pregnancy.Risk of preterm delivery,hypovolumic &allergic reax.
thymoma, which is a potentially invasive tumor that must be removed, is found in few cases.
This is puzzling because no close correlation exists between maternal disease severity and neonatal myasthenia, and no correlation exists between the occurrence of neonatal myasthenia gravis and maternal anti-AChR antibody titers. These unpredictable results could be due to the protective role of alpha-fetoprotein in neonatal myasthenia gravis. Alpha-fetoprotein has been shown to inhibit the binding of myasthenia gravis antibody to its receptor.
Pregnancy in a young girl with Myasthenia Gravis.
DR. ANITA AGGARWAL
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.
In 2003- Pt. suddenly developed ptosis and diplopia she
was shown to opthalmologist and given conservative
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
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
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
Ante Natal Period.
She got married in 2011. Conceived after 6 months
spontaneously.She continued on Distinone through
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
In late sec. trimester -she started having oedema
Third trimester-IUGR noted. Put on amino
acids, antioxidants dietary changes and adv. rest.Serial
USG with doppler studies done to monitor growth.
sugar, urine,LFT(low A:G ratio).Bl.group-O neg ICT
neg.Viral markers – NR
GPE & Systemic exam- unremarkable.
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.
. 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
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
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).
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
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 –
Ach is rapidly hydrolized by AchE present
in synaptic folds,diffuse away from
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.
Acetylcholine receptor (AChR) antibodies are detected
in approximately 85% of patients with generalized
myasthenia gravis, who are categorized as
Anti-AChR antibodies reduce the number of available
AChR sites with which acetylcholine can interact to
induce local depolarization and subsequent muscle
Muscular weakness, the primary symptom in patients
with generalized myasthenia gravis, results.
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
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.
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.
Thus, evidence supports a correlation between thymus
activity and the incidence of myasthenia gravis.
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
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.
Blood test- To detect antibodies
Nerve Stimulation test
Edrophonium (Tensilon test )
Imaging Scan CT or MRI (thymus)
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.
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.
, 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
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
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
Systemic lupus erythematosus
Autoimmune hemolytic anemia
Thymic abnormalities are also associated with myasthenia
gravis. As many as 50-60% of patients have
lymphofollicular hyperplasia, and 10-20% have a thymoma
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
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)
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.
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
IVIG-0.4- 1mg/kg.Effect may last upto 3 mth
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 .
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
Single dose only
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
1-1.5 g bid
Inhibition of purine synthesis by denovo pathway
Inhibits proliferation of lymphocytes
Lack of adverse side effects
50mg/d should be used
2-3 mg/kg in children
10 % develop idiosyncratic reactions
Not to give allopurinol.
Cyclosporine ,tacrolimus as adjunctives
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
Thymectomy-Thymectomy is recommended for most
It improves the disease course and can improve
remission. Thymectomy is thought to remove an
antigen source and reduce an anti-AChR antibody
Thymectomy is performed when the disease is in
Other Treatment considerations
Monitoring patients for infection especially those on
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
Potassium rich diet and adequate rest.
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.
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
Breastfeeding by the mother with myasthenia gravis is safe if she is
following a treatment course that utilizes pyridostigmine or
Mothers with myasthenia gravis being treated with
azathioprine, methotrexate, mycophenolate mofetil, or
cyclophosphamide should avoid breast feeding.
Drugs to be avoided in MG
Not all patients have adverse effects
Non depolarizing muscle
Counselling about the risks
Joint obs and Physician care
Plasmapheresis in resistant cases