Myasthenia gravis in pregnancy

1. MYASTHENIA GRAVIS AND
PREGNANCY
BY
AHMED ABD EL ALEEM
FACULTY OF MEDICINE
ZAGAZIG UNIVERSITY

3. • ETIOLOGY
• IMPACT IN PREGNANCY
• NEONATAL IMPACT
• EPIDEMIOLOGY
• DIFFERENTIAL DIAGNOSIS
• PLASMAPHERESIS AND INTRAVENOUS IMMUNOGLOBULIN THERAPY
• THYMECTOMY
• GUIDLINES
BY THE END OF LECTURE YOU WILL KNOW

4. ETIOLOGY
• UNDERLYING PATHOLOGY IS THE AUTOIMMUNE PRODUCTION OF IMMUNOGLOBULIN G
(IGG) ANTIBODIES DIRECTED TOWARD RECEPTORS ON THE POSTSYNAPTIC MEMBRANE
AT NEUROMUSCULAR JUNCTIONS (NMJS).
• ACETYLCHOLINE RECEPTOR (ACHR) ANTIBODIES ARE DETECTED IN APPROXIMATELY
85%
• THE MEMBRANE PROTEIN MUSCLE-SPECIFIC TYROSINE KINASE (MUSK) ANTIBODIES

5. PATHOPHYSIOLOGY
• IGG AB INTERACT WITH THE POSTSYNAPTIC ACHR AT THE NICOTINIC
NEUROMUSCULARJUNCTION(NMJ).
• THIS REDUCES THE NUMBER OF FUNCTIONAL RECEPTORS BY BLOCKING ACH
ATTACHMENT, BY INCREASING THE DEGRADATION OF RECEPTORS AND BY
COMPLEMENT INDUCED DAMAGE TO THE NMJ

6. EPIDEMIOLOGY
• WORLDWIDE INCIDENCE IS RECORDED AS RANGING FROM 20-100 PER MILLION
• WORLDTHE PREVALENCE OF MYASTHENIA GRAVIS IN PREGNANCY IS ESTIMATED AT 1 IN
20,000.
• BOTH SEXES ARE AFFECTED BY MYASTHENIA GRAVIS, AND THE OVERALL FEMALE-TO-
MALE RATIO IS 2:1. THE PREVALENCE OF EARLY ONSET (< 40 Y) MYASTHENIA GRAVIS IS
NEARLY 3 TIMES HIGHER IN FEMALES THAN IN MALES, WHILE THE PREVALENCE OF
LATE-ONSET MYASTHENIA GRAVIS (>50 Y) IS MORE PREVALENT IN MALES THAN IN
FEMALES.

8. IMPACT IN PREGNANCY
• UNPREDICTABLE ..WORSEN…IMPROVE….OR UNCHANGED.
• 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.
• APPROXIMATELY 60% OF EXACERBATIONS OCCURRED DURING THE FIRST
TRIMESTER, AND APPROXIMATELY 28% OF PATIENTS DETERIORATED IMMEDIATELY
AFTER DELIVERY.

9. IMPACT IN PREGNANCY
• REPORTED A RARE CASE OF BONE MARROW SUPPRESSION IN A PATIENT WHO EXPERIENCED
LEUKOPENIA AND THROMBOCYTOPENIA.
• APPROXIMATELY 20% OF PATIENTS EXPERIENCE RESPIRATORY CRISES THAT REQUIRE
MECHANICAL VENTILATION ….??
• INFECTIONS DUE TO DECREASED IMMUNITY , SOME EXACERBATIONS CAN BE LINKED TO
THE ANXIETY AND PHYSIOLOGIC STRESS OF PREGNANCY , ALSO, THE LUNGS DO NOT
BECOME FULLY INFLATED, BECAUSE THE DIAPHRAGM IS ELEVATED DURING PREGNANCY.

10. • AN ASSOCIATION BETWEEN MYASTHENIA GRAVIS AND PREECLAMPSIA AND
REASONED THAT ALTERED IMMUNE STATUS COULD BE AN ETIOLOGIC FACTOR IN
PREECLAMPSIA. PREECLAMPSIA MAY ALSO BE PROBLEMATIC FROM A
PHARMACOLOGIC STANDPOINT, BECAUSE MAGNESIUM SULFATE IS
CONTRAINDICATED IN MYASTHENIC PATIENTS. IN THE EVENT THAT ECLAMPSIA
DOES PRESENT IN THE PREGNANT PATIENT WITH MYASTHENIA GRAVIS, PHENYTOIN
IS THE CURRENTLY ACCEPTED METHOD OF TREATMENT.
IMPACT IN PREGNANCY

12. DELIVERY
• TIME ACCORDING TO OBSTETRIC INDICATIONS
• MOODE ACCORDING TO OBSTETRIC INDICATIONS
• 1ST STAGE OXICYTOCIN ALLOWED
• 2ND STAGE ALTHOUGH SMOOTH MUSCLE IS NOT AFFECTED BY AUTOANTIBODIES
AND THE UTERUS IS NOT COMPROMISED, THE SECOND STAGE OF LABOR INVOLVES
STRIATED MUSCLE. THE PATIENT MAY BECOME EXHAUSTED DURING LABOR AND
MAY REQUIRE ASSISTANCE. OPERATIVE VAGINAL DELIVERY HAS BEEN
RECOMMENDED.
• CESAREAN DELIVERY (30%)
• ANASTHESIA THE HAZARDS OF ANESTHESIA MUST BE KEPT IN MIND, BECAUSE
PATIENTS ARE SENSITIVE TO SEDATIVES AND NARCOTICS ,MUSLE RELAXANT.
• PURPURIUM CRISIS

13. NEONATAL IMPACT
• NEONATAL MYASTHENIA GRAVIS
• 10-20%
• AFFECTED BABIES SHOW RESPIRATORY DISTRESS AND INADEQUATE SUCK.
• SELF-LIMITED AND LASTS APPROXIMATELY 3 WEEKS.
• 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.

14. NEONATAL IMPACT
• MALFORMATIONS….. PULMONARY HYPOPLASIA.
• PREMATURITY CHRONIC HYPOXIA , IATROGENIC

15. DIFFERENTIAL DIAGNOSIS
• THE DIFFERENTIAL DIAGNOSIS OF MYASTHENIA GRAVIS INCLUDES CONDITIONS
ASSOCIATED WITH WEAKNESS OF MUSCLES, SUCH AS THE FOLLOWING:
• LAMBERT-EATON MYASTHENIC SYNDROME
• BOTULISM
• HYPOTHYROIDISM
• INTRACRANIAL MASS LESION
• PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA
• DRUG-INDUCED MYASTHENIA GRAVIS

16. • PLASMAPHERESIS
• EXPENSIVE , A VERY EFFECTIVE TREATMENT
• PROCEDURE USED IN PATIENTS IN MYASTHENIC CRISIS. TOGETHER WITH STEROIDS
• , PLASMAPHERESIS IS. IT CONSISTS OF 3-6 EXCHANGES OF 2-3 L OVER 1-2 WEEKS.
IT IS SAFE DURING PREGNANCY.
• AS THE ETIOLOGY OF PRETERM DELIVERY IS UNKNOWN, PLASMAPHERESIS IS (OR MAY
BE) ASSOCIATED WITH PRETERM DELIVERY. OTHER COMPLICATIONS CAN OCCUR
FROM HYPOVOLEMIC REACTIONS OR ALLERGIES. LARGE HORMONE SHIFTS MAY
CAUSE PRETERM DELIVERY. PATIENTS UNDERGOING PLASMAPHERESIS SHOULD BE
MONITORED.
• INTRAVENOUS IMMUNOGLOBULIN
• INTRAVENOUS IMMUNOGLOBULIN IS ALSO USEFUL IN PATIENTS IN MYASTHENIC
CRISIS. IT IS THOUGHT TO INTERFERE WITH ANTI-ACHR ANTIBODIES. IT IS INFUSED
AT 0.4 G/KG/D FOR 5 CONSECUTIVE DAYS. IMPROVEMENT IS NOTICEABLE IN 3-21
DAYS AND LASTS AS LONG AS 3 MONTHS.

17. 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.

18. Guidelines
Planning for pregnancy should be instituted well in advance to allow time
for optimization of myasthenic clinical status and to minimize risks to the
fetus.
Multidisciplinary communication among relevant specialists should occur
throughout pregnancy, during delivery, and in the postpartum period.
Provided that their myasthenia is under good control before pregnancy,
the majority of women can be reassured that they will remain stable
throughout pregnancy. If worsening occurs, it may be more likely during
the first few months after delivery.
Oral pyridostigmine is the first-line treatment during pregnancy. IV
cholinesterase inhibitors may produce uterine contractions and should not
be used during pregnancy.

19. Chest CT without contrast can be performed safely during pregnancy, although the risks of
radiation to the fetus need to be carefully considered. Unless there is a compelling indication,
postponement of diagnostic CT until after delivery is preferable.
Thymectomy should be postponed until after pregnancy as benefit is unlikely to occur during
pregnancy.
Current information indicates that azathioprine and cyclosporine are relatively safe in
expectant mothers who are not satisfactorily controlled with or cannot tolerate
corticosteroids. Current evidence indicates that mycophenolate mofetil and methotrexate
increase the risk of teratogenicity and are contraindicated during pregnancy. Although this
statement achieved consensus, there was a strong minority opinion against the use of
azathioprine in pregnancy. Azathioprine is the nonsteroidal IS of choice for MG in pregnancy
in Europe but is considered high risk in the United States. This difference is based on a small
number of animal studies and case reports.

20. PLEX or IVIg are useful when a prompt, although temporary, response is required during pregnancy.
Careful consideration of both maternal and fetal issues, weighing the risks of these treatments
against the requirement for use during pregnancy and their potential benefits, is required.
Spontaneous vaginal delivery should be the objective and is actively encouraged.
Magnesium sulfate is not recommended for management of eclampsia in MG because of its
neuromuscular blocking effects; barbiturates or phenytoin usually provide adequate treatment.
All babies born to myasthenic mothers should be examined for evidence of transient myasthenic
weakness, even if the mother’s myasthenia is well-controlled, and should have rapid access to
neonatal critical care support