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Gynecologyandobstetrics.jacobspublishers.comJacobs Journal of Gynecology and Obstetrics
Myasthenia Crisis in Pregnancy
Roopan K. GILL MD1*, Tung Thanh Cao NGUYEN MD, FRCPC2, Pierre J. HUARD MD, FRCSC3, Hisham A. KHALIL
1The University of Ottawa Department of Obstetrics and Gynecology, Canada
2The University of Ottawa, Division of Neurology, Canada
3The University of Ottawa, Department of Obstetrics and Gynecology, Canada
4The University of Ottawa, Department of Obstetrics and Gynecology, Canada
*Corresponding author: Dr. Roopan K. Gill, 211 Carleton Avenue, Ottawa, ON, K1Y0J5, Tel: (613) 796-4307; Email: [email protected]
Copyright: 2015 Roopan
weeks gestational age . Her symptoms specifically included bulbar, limb, ocular and respiratory weakness. She required Myasthenia Gravis (MG) is an autoimmune disorder of the neu- immediate intubation, mechanical ventilation and plasma- romuscular junction characterized by fluctuating weakness of pheresis. skeletal muscles. It is caused by autoantibodies against post synaptic acetylcholine receptor (AChR) .
Her MG diagnosis was made four years prior to this pregnancy. She had a history of one previous myasthenia crisis outside of In pregnancy, myasthenia gravis has both maternal and fetal pregnancy. This required admission to the intensive care unit. implications, and can manifest in various degrees of weakness The patient had a history of poor compliance with medications, and fatigability of skeletal muscles. Respiratory failure is a life developmental delay, anorexia and a significant psychiatric threatening complication of this rare disorder . history. Her myasthenia gravis was being managed with aza- thioprine, prednisone, IVIG and mestinon prior to pregnancy. We present a rare case of myasthenia crisis with respiratory failure in pregnancy as well as a review of the available litera- During pregnancy she was to continue with mestinon 60 mg ture. We highlight the importance of a multispecialty approach three times daily, prednisone 20 mg daily and IVIG 1g/kg every in the management of myasthenia gravis in pregnancy. We also two to four weeks, which was being managed by her neurolo- wish to highlight management issues in the postpartum and gist. Unfortunately the patient was poorly adherent to this reg- neonatal period. imen. She developed progressive weakness during the week prior to presentation, which manifested predominately as dys- The patient presented in this case provided informed written phagia secondary to bulbar weakness.
Upon admission to our facility, she was in severe myasthenia crisis with respiratory failure at 32 weeks gestation . She A 29-year-old patient with Myasthenia Gravis presented with was immediately admitted to the intensive care unit for intu- a myasthenia crisis resulting in respiratory depression at 32 bation and management. Her blood gases prior to intubation Cite this article: Gill R K. Myasthenia Crisis in Pregnancy. J J Gynec Obst. 2015, 2(4): 021. Jacobs Publishers were: pH 7.26/ pCO 36/ pO 32/ HCO 16/base excess -10.0, . Approximately one third of patients remain the same, one with a calculated oxygen saturation of 51% and measured at third improve and the remaining one third worsen [4,5]. Clin- 63%. A fetal ultrasound including cord dopplers and biophys- ical dilemmas that may be faced by the neurologic and obstet- ical profile were normal on the day of presentation. During her rical teams can include: 1) appropriate method of delivery that admission she received plasmapheresis (PLEX), responding would be safest for the patient given myasthenic crisis and 2) well after five doses and was eventually transitioned to pred- discussing treatment most appropriate for her myasthenia to nisone and mestinon. Her blood work abnormalities consisted stabilize/optimize in setting of impending labour.
of a fibrinogen level of 0.8 and hemoglobin of 70, which were investigated and found to be secondary to the PLEX treatment. Treatment of MG in Pregnancy
The patient was weaned from the ventilator after several days with close monitoring by both the intensive care and neurolo- A neurologist and an obstetrician should see patients with MG gy team. Respiratory status was monitored by SVC (Slow Vital relatively frequently throughout the pregnancy. Therapy must Capacity), MIPs (Maximum Inspiratory Pressure) and MEPs be chosen considering severity of disease and potential side ef- (Maximum Expiratory Pressure). Her MIPs and MEPs were fects on fetus . Treatment of MG during pregnancy requires below an absolute value of 15 during the first few days of ad- that women be educated to not over exert themselves to avoid mission with a significantly decreased SVC. Her SVC increased unnecessary fatigue. Emotional stress and lack of sleep should to 2.0 and her MIPS and MEPS were satisfactorily stable for be kept to minimum . Oral anticholinesterases are the drug extubation after several days. Monitoring continued by the of choice for symptomatic treatment of MG . (Class B) neurology team. While in the intensive care unit she was close- ly followed by obstetrics with serial non-stress tests and ob- Immunosuppressant drugs such as corticosteroids should be stetrical ultrasounds, which were found to be normal. She did avoided in women with purely ocular symptoms or very mild have signs and symptoms of threatened preterm labour, which generalized weakness [1,8]. Corticosteroid therapy presents required close fetal and maternal monitoring. little if any teratogen risk to fetus, and only slight increase in incidence of cleft palate has been reported . IVIG has been She was transferred from the intensive care unit once she was proven to be effective and safe for deteriorating MG in preg- extubated and remained in hospital under Neurology until she nancy however it has been postulated that there may be an was full term. A decision was made to proceed with vaginal increased risk of venous thromboembolism due to higher risk route of delivery, as she was compliant to medications allowing of hyperviscosity and volume overload during pregnancy [1,2]. for a safe, controlled procedure for delivery. The only indication Mycophenolate mofetil, methotrexate and cyclophosphamide for a cesarean section in her context would have been due to are contraindicated in pregnancy . Azathioprine is not rec- fetal concerns. The patient was induced at 37 weeks to accom- ommended in pregnancy as exposed fetuses are at increased plish delivery while she was medically optimized. Throughout risk of myelosuppression . Due to the theoretical risk of the course of her induction and labour she was stable. She thromboembolism with IVIG, PLEX was used in the above pa- obtained an epidural anesthetic. She had a prolonged passive tient to treat her myasthenic crisis. second stage of labour. She had a successful vacuum-assisted vaginal delivery of a live female weighing 3102 grams with AP- Hypoventilation is a risk during pregnancy because MG weak- GARS of 9 and 9 at one and five minutes respectively and did ens respiratory muscles, which, in addition to the elevation of not show any signs of muscular weakness. diaphragm caused by enlarging uterus, may cause reduced ox- ygenation . Respiratory crises requiring mechanical ventila- The patient had an uncomplicated postpartum period and was tion constitute the most severe complications [2,9]. Therefore discharged home in stable condition with follow-up with her management of a myasthenia crisis requires careful monitor- Obstetrician and Neurologist. Postpartum management of ing in an intensive care setting . Together with steroids, her myasthenia gravis consisted of IVIG to be reinitiated on a plasmapheresis should be used in pregnant women in myas- monthly basis, continuation of mestinon and prednisone with thenia crisis. The literature suggests that this is safe during recommencement of Azathioprine. Thymectomy is planned pregnancy . Patients undergoing plasmapheresis should following the puerperium. always be carefully monitored because complications may oc- cur, such as hypovolemic reactions or allergies [1,11]. In ad- dition, large hormone shifts may cause preterm delivery . Risk of preterm birth may occur in the setting of congenital The management of MG in pregnancy requires a multispeciality myasthenia, primarily as a consequence of associated polyhy- team including a neurologist, maternal fetal medicine obstetri- dramnios . Screening for asymptomatic bacteriuria should cian, neonatologist and an obstetric anesthetist. Involvement be performed and appropriate treatment for urinary tract in- of these should be ensured prenatally and during labor and fections is required especially for patients on steroids [1,10].
delivery. The course of MG during gestation is highly variable and unpredictable and can change in subsequent pregnancies Cite this article: Gill R K. Myasthenia Crisis in Pregnancy. J J Gynec Obst. 2015, 2(4): 021. Jacobs Publishers is important patients are seen by a physician within the first three weeks after delivery. Closer observation is recommend- It is rare that MG patients develop pre-eclampsia during preg- ed for infants of mothers with myasthenia gravis secondary nancy however the coexistence of these disorders may pro- to muscle-specific tyrosine kinase (MuSK) antibodies (which duce high degree of morbidity and mortality for both mother may be associated with early and more severe neonatal mani- and fetus . Of note the use of magnesium sulfate is con- festations). traindicated in patients with MG. Magnesium interferes with Thymectomy has been recommended in certain populations the neuromuscular transmission by inhibiting the release of for treatment of MG and is primary disease controlling modal- acetylcholine. In addition, it may competitively block calcium ity. It has been shown that incidence of exacerbations are high- entry at the motor nerve terminal thus potentiating the nega- er in nonthymectomized than thymectomized patients, while tive effects of MG on pregnancy. there is no difference in neonatal MG between the two groups Mode of Delivery
. Complete remission has been described in approximate- ly 45% of thymectomized patients and clinical improvement Generally, mode of delivery can be safely completed vaginally. is not noted until years after surgery. Therefore, women may MG does not affect uterine smooth muscle therefore the first undergo thymectomy after delivery as there is not enough evi- stage of labor is not compromised. The second stage involves dence to suggest improved prognosis of MG during pregnancy striated muscles, which are at risk for fatigue. The patient may [9,14]. Breastfeeding is not contraindicated in women taking become exhausted during labor and will require assistance cholinesterase inhibitors or prednisone, although it is suggest- with forceps or a vacuum . Surgical delivery poses sever- ed to avoid feeding for four hours after taking these medica- al risks for MG patients and should be reserved for patients tions [1,15].
with severe myasthenia exacerbation, myasthenia crisis and Conclusion
obstetrical indications. In the described case, since both sur- gical and vaginal delivery were associated with potential risks Myasthenia Gravis can have an unpredictable course in preg- given her recent crisis, not one was clearly safer than the other, nancy. Its peak lifetime incidence is in women of reproductive ultimately, the obstetrics team chose assisted vaginal delivery. age. Respiratory insufficiency is a potentially life threatening Generally epidural anesthesia should be preferred and narcot- complication of poorly controlled Myasthenia Gravis. An inter- ic analgesia and muscle relaxants avoided [1,10].
disciplinary approach including Obstetricians, Anaesthetists, Neurologists, Intensivists and Neonatologists is essential to optimize the outcome for both the woman and neonate. Every newborn of MG mothers should be carefully monitored for signs of muscle weakness and impaired respiratory and References
bulbar function. It is not possible to predict the occurrence and severity of neonatal MG . Placental transfer of IgG an- 1. tibodies against fetal AChR can cause arthrogryposis multiplex congenital (AMC), a syndrome of multiple congenital joint con- 2. tractures in utero from lack of fetal movement and abnormal joint formation . Approximately 10-20% of infants born to MG women show signs of neonatal MG (NMG) . Evidence suggests that there may be some correlation between mater- 3. nal antibody levels and severity of NMG however this is not absolute . Some literature suggests that alfa-fetoprotein (AFP) may be protective for newborns as it inhibits ACHR ab 4. binding . Neuromuscular symptoms in newborns mani- fest clinically within first 12 – 48 hours postpartum . Fetal complications such as pulmonary hypoplasia, arthrogyposis 5. congenital and nonspecific hyperbilirubinemia have been re- ported [1,10]. Therefore MG patients should be informed that though clinical state throughout pregnancy may have been sta- 6. ble, fetal complications might occur. MG exacerbations may occur within the postpartum period. It Cite this article: Gill R K. Myasthenia Crisis in Pregnancy. J J Gynec Obst. 2015, 2(4): 021. Jacobs Publishers Cite this article: Gill R K. Myasthenia Crisis in Pregnancy. J J Gynec Obst. 2015, 2(4): 021.
Int. J. Technology Management, Vol. 64, No. 1, 2014 Image-focused social media for a market analysis of tourism consumption María Pilar Latorre-Martínez* and Tatiana Iñíguez-Berrozpe Escuela de Turismo Universitaria de Zaragoza, Plaza Ecce Homo, 3, 50003, Zaragoza, Spain E-mail: [email protected] E-mail: [email protected] *Corresponding author