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
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.
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. Women are affected in their second and third decades of life more commonly, so their reproductive years are affected. In the case of maternal MG, both the mother and child can develop symptoms of weakness and progressive fatigability of the skeletal muscles.
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.
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. In general, MG does not have any severe adverse effects on pregnancy. There is no increase risk of preeclampsia in pregnancy with MG. 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.
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. 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.
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. 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. Surgery can be stressful for women with MG hence cesarean section should be performed only for obstetric indications. 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.
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.
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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