Author
Information
Patil S*, Tiwari N**, Shah A***, Chauhan AR****
(* Fourth Year Resident,
** Assistant Professor, *** First Year Resident, **** Professor, Department of
Obstetrics and Gynecology, Seth G.S. Medical
College and K.E.M.
Hospital , Mumbai , India
Abstract
Myasthenia gravis is
caused by impaired function of acetylcholine receptors at neuromuscular
junction due to auto antibodies against them. This autoimmune disorder is characterized
by a variable combination of weakness in ocular, bulbar, limb and respiratory
muscles. Affected patients, most often young women, usually present with
weakness after repetitive muscle use. The course of myasthenia gravis in
pregnancy and its influence on the outcome of pregnancy are not predictable. We present a
case of maternal myasthenia gravis in pregnancy and its successful outcome
using a multidisciplinary diagnostic and therapeutic approach.
Introduction
Myasthenia gravis (MG)
is an autoimmune disorder at the neuromuscular junction due to auto antibodies
against the acetylcholine receptor, leading to an impaired nerve impulse
transmission to striated muscle fibers. It is due to abnormal regulation of T-
cells and autoantibody production against nicotinic acetylcholine receptors
which are present on the neuromuscular end- plate of skeletal muscle. It may be
congenital or acquired and is clinically characterized by progressive weakness
of skeletal muscles. Prevalence of MG is 10.42 to 12.99 per 100,000 individuals
and nearly 2/3rds are female.[1] Women are affected in their second
and third decades of life more commonly, so their reproductive years are
affected.[2] In the case of maternal MG, both the mother and child can develop
symptoms of weakness and progressive fatigability of the skeletal muscles.
Case
Report
Mrs. VJ, 28 year old
primigravida with 33 weeks of gestation, diagnosed case of MG was referred to
our tertiary care center from private hospital in view of oligohydramnios and
for neurological evaluation. Patient was a diagnosed case of MG since December
2013, when she had symptoms of dysphagia, dysarthria and diplopia. She was
investigated and her acetylcholine receptor autoantibodies were found to be
positive (9.6 nmol/L; normal value of <0.4 nmol/L). She was evaluated by a
neurologist and treated with tab prednisolone 15 mg, tab pyridostigmine 60 mg
(acetylcholine esterase inhibitor), tab azathioprine 50 mg (immunosuppressant)
and esmoprazole 20 mg daily. Once she was symptomatically better, dosage of
these drugs was tapered over 2 months, after which she was on maintenance with
tab prednisolone 10 mg once daily and was instructed to take tab pyridostigmine
60 mg, only if symptoms were aggravated.
Thereafter she conceived
and was continued on two medications (prednisolone and pyridostigmine). She
registered in private hospital for routine antenatal care. During evaluation,
amniotic fluid index (AFI) on USG was 6 - 7 cm for which she referred to our
hospital and admitted. Doppler showed AFI of 3 cm with absent diastolic flow,
and expected fetal weight of 1.4 kg; hence decision for cesarean section was
taken. Neurologist opinion was sought; they advised to continue the same drugs along
with injection hydrocortisone 50 mg intravenous preoperatively, to be continued
for 48 hours in post operative period. After corticosteroids for fetal lung
maturity, patient underwent an uneventful cesarean section under spinal
anesthesia and delivered a female child of 1.2 kg with Apgar score of 9/10.
Though general anesthesia is preferred in cases with bulbar weakness or
respiratory inadequacy, our patient had history of ocular myasthenia, hence
regional anesthesia was given. Postoperatively, she was continued on intravenous
hydrocortisone 50 mg 8 hourly for 48 hours.
The newborn was
transferred to the pediatric unit for evaluation and did not show any signs of
neonatal myasthenia initially nor in the course of time; the baby was
discharged after adequate weight gain on day 14. Mother was restarted on tab
prednisolone 10 mg and tab pyridostigmine 60 mg daily, breastfeeding was
initiated and was discharged. Patient is on regular follow up.
Discussion
Battochi et al observed
that 42% of patients with myasthenia were stable during pregnancy, whereas
about 39% showed an improvement and nearly 19% showed an exacerbation of
symptoms.[3] In general, MG does not have any severe adverse effects on
pregnancy.[4] There is no increase risk of
preeclampsia in pregnancy with MG.[5] Maternal mortality risk is highest
within the first year of diagnosis of MG and risk becomes minimal after 7 years
of diagnosis; hence these women should delay pregnancy for at least 2 years
after diagnosis of disease.[3]
Pyridostigmine and
neostigmine are commonly used in treatment of MG. During pregnancy, treatment
should not be stopped; however the dose of drugs may need to be altered
depending on severity of the disease or exacerbation.[4] Medications that
aggravate the symptoms of MG by enhancing the effect of acetylcholine receptor
antibodies are contraindicated in patients with myasthenia gravis. These drugs
include neuromuscular blocking agents (magnesium sulfate, vecuronium),
antiarrhythmic drugs (procainamide, quinidine), and local anesthetics (esters,
lignocaine), as well as antibiotics from the aminoglycoside, quinolone and
macrolide groups.[5]
Antenatally, patients
with MG may predispose to preterm labor and premature preterm rupture of
membranes, mainly due to steroids and acetylcholine esterase inhibitors.
Vaginal delivery is recommended for women with myasthenia gravis.[6] However,
patient may need operative vaginal delivery due to involvement of voluntary
muscles of pelvic floor contributing to poor bearing down during second stage
of labor. During labor and delivery, epidural anesthesia is recommended.[7]
Surgery can be stressful for women with MG hence cesarean section should be
performed only for obstetric indications.[6] 10% to 20% of neonates can develop
transient neonatal MG due to placental transfer of IgG antibodies in the second
and third trimesters. The neonate may develops symptoms of transient MG 2 to 4
days after birth, which includes respiratory difficulty, weak cry, muscle
weakness, poor sucking and ptosis, requiring close monitoring.
Conclusion
Myasthenia gravis when
associated with pregnancy should be considered as a high-risk disease as its
course is unpredictable. Mild to severe life-threatening conditions can occur
especially due to generalized weakness, particularly respiratory insufficiency
in the parturient as well as the newborn. It is necessary to be aware of this
disease and its multidisciplinary diagnostic and therapeutic management.
References
- Lee HS, Lee HS, Shin HY, Choi YC, Kim SM. The Epidemiology of Myasthenia Gravis in Korea. Yonsei Med J. 2016; 57(2): 419-25.
- Chaudhry SA, Vignarajah B, Koren G. Myasthenia gravis during pregnancy. Can Fam Physician. 2012 Dec; 58(12): 1346-9.
- Batocchi AP, Majolini L, Evoli A, Lino MM, Minisci C, Tonali P. Course and treatment of myasthenia gravis during pregnancy. Neurology. 1999; 52(3): 447–52.
- Ferrero S, Esposito F, Biamonti M, Bentivoglio G, Ragni N. Myasthenia gravis during pregnancy. Expert Rev Neurother. 2008; 8(6): 979–88.
- Gold R, Hohlfeld R, Toyka KV. Progress in the treatment of myasthenia gravis. Ther Adv Neurol Disord. 2008 Sep; 1(2): 36-51.
- Ferrero S, Pretta S, Nicoletti A, Petrera P, Ragni N. Myasthenia gravis: management issues during pregnancy. Eur J Obstet Gynecol Reprod Biol. 2005; 121(2):129–38.
- Djelmis J, Sostarko M, Mayer D, Ivanisevic M. Myasthenia gravis in pregnancy: report on 69 cases. Eur J Obstet Gynecol Reprod Biol. 2002; 104(1): 21–5.
Patil S, Tiwari N, Shah A, Chauhan AR. Successful Outcome Of Pregnancy In A Patient With Myasthenia Gravis. JPGO 2015. Volume 3 No. 4. Available from: http://www.jpgo.org/2016/04/successful-outcome-of-pregnancy-in.html