Myaesthenia Gravis in Pregnancy.

Dr. Mridula A. BenjaminDept of Obs and Gyn, RIPAS Hospital, Brunei

M.J. IC:31-001064

22 yrs. G2P1. Self conception. Non consanguineous. 1st preg:

LMP: ? July 2004.

Unbooked case.

Emergency LSCS was done in Jan 2005 at 30 wks for severe APH.

No significant past medical and family history.

24/09/05: A&E for sore throat, loss of voice, unable to swallow and sweating.

BP: 96/58 mm.Hg. ENT: Diagnosed fx. Aphasia after normal fibroscopy. 25/09: Chest review: Ocular fatigue and facial

diaplegia. No obvious motor weakness. Combined resp and metab acidosis. 26/09: Neuro review: Patient dyspnoiec, tachycardic. ANA, Anti-DNA, Tensilon test

ANA- Mixed homogenous 1:40. Anti-DNA: Negative. Tensilon test: Positive. Repetitive test: +ve. EMG: Muscle weakness. Diagnosed as Myas. Crisis. Treated with pyridostigmine, prednisolone and

Azathioprine. Discharged from Neuro on 15/10. Referred by Neuro to O&G on 29/10 for

pregnancy after stopping Azathioprine.

Seen in O&G on 09/11. LMP: 29/Aug/05. EDC: 6/6/6 USS: 10 wks pregnant. Advised to continue pyridostigmine and

prednisolone.Given folic acid, adv NT Booked into high risk clinic on 22/11. Antenatal screening: NAD. Regular follow ups. Normotensive

USS at 18 wks: No anomalies. Subsequent USS at 30, 35 and 37 wks showed

adequate growth. USS on 16/05: Fetal wt of 3059 gms and AFI of

13. Placenta posterior and upper segment. Paeds counselling on 16/05: Told about resp.

insuff. requiring ventilation, feeding difficulties, congenital MG.

Admitted with tightenings on 29/05/06. Counselled for VBAC. Neuro review was done with adv. of Inj

Hydrocortisone 100mg 6 hrly in active labour. On 31/05 : SROM at 1:40 am. Contractions 1: 5: 40, CTG-R. VE: os 1.5, thick cervix, liquor clear, memb

absent, stn high. Was given sedation.

Reviewed by on call team morning. Anaemic, Hb; 7.8, given PCV. In view of prolonged latent phase, MG, prev.

LSCS, high presenting part, LSCS done. Post operative uneventful. Started on medication. Discharged on day 5 after neuro review.

Myasthenia gravis Autoimmune neuromuscular disease

characterized by weakness and fatigue of the skeletal muscles.

Female-to-male ratio is 2:1. Usually affects women in third decade of life. Worldwide prevalence: ~40 cases per million.

Incidence is 1 in 20,000-40,000.

Pathology Production of autoantibodies against human

acetylcholine receptors (AChRs), usually immunoglobulin G.

This is detected in as many as 90% of patients. Antibodies interfere with the conduction of

impulses across myoneural junctions by decreasing the number of available AChRs at neuromuscular junctions.

In pregnancy Course during pregnancy is hard to predict. Patients may have disease exacerbation (40%),

remission(30%), or no change (30%). Pregnant patients face risks of exacerbation,

respiratory failure, adverse drug response, crisis, and death.

Worsens by emotional distress, systemic illness and hot temperature.

Maternal complications ~ 20% of patients experience respiratory crisis that

require mechanical ventilation. Association between MG and preeclampsia.

Altered immune status could be an etiologic factor in preeclampsia. MgSO4 is contraindicated.

Bone marrow suppression. Hydramnios

Contd. Complicated labor: 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. Forceps delivery has been recommended.

Myaesthenia crisis can occur: Parenteral drugs.

Fetal complications Fetal abnormalities: pulmonary hypoplasia and

arthrogryposis. Premature delivery occurs in ~36.5% of cases. B

sympathomimetics can be used. Growth restriction. Still births (2.7%) and miscarriages (4.7%). Neonatal MG: Rates:10-20% Does not appear at birth. Usually temporary, lasting only a few weeks.

Plauche et al Exacerbations occurred in approximately 41% of

patients during pregnancy and in 29.8% of patients postpartum.

Approximately 4% of patients died because of worsening of the disease or because of treatment complications.

Batocchi et al

~ 60% of exacerbations occurs during the first trimester.

~ 28% of patients deteriorates immediately after delivery.

Premature delivery occurs in 7.4% patients. Caesarean delivery is performed in 30%. No correlation between MG severity before and

during pregnancy.

History Symptoms: ptosis, diplopia, breathing difficulty,

dysphagia, and weak limbs. Intermittent ptosis and diplopia are usually the

initial reported symptoms. Symptoms become generalized within 1 year and

fluctuate in severity. Worsen with exertion, emotional distress and

systemic illness and are relieved with rest.

Physical examination

Muscle strength assessed by quantitative studies: eg. patient squeeze the examiner's hand repeatedly, flex her arm against resistance, asking the patient to smile.

Deep tendon reflexes are preserved. Check for diplopia and ptosis.

Differential diagnosis Eaton-Lambert myasthenic syndrome. Botulism. Hyperthyroidism. Neurasthenia. Intracranial mass lesion. Progressive external ophthalmoplegia. Drug-induced MG.

Tests Screen for other autoimmune diseases. Test of choice: Tensilon test: IV injection of

edrophonium (cholinesterase inhibitor). This increases the amount of ACh available. Clinical improvement occurs in 10-60 seconds and lasts for approximately 10 minutes.

Most specific test: Anti-AChR antibody levels. EMG: Reduced evoked muscle potential. CT scans: For the thymus.

Drugs to avoid

Narcotics, tranquilizers, barbiturates. Inhalation anesthetics (ie, halothane,

trichloroethylene, ether). Magnesium and lithium salts. Penicillamine. Beta-adrenergic agents. Aminoglycoside antibiotics, neomycin,

tetracycline, lincomycin.

Management Individualized therapy by neurologist and an

obstetrician/gynecologist during pregnancy. Crisis can occur due to worsening disease

processes, reduced effects of anticholinesterase drugs, or overdose of anticholinesterase medication.

Management of myasthenic crisis requires careful monitoring. ABG values must be monitored in patients with increasing weakness.

Patient has to be seen every 2 wks in the 1st 2 trimesters and every week in 3rd.

Avoid undue physical and emotional stress. Exacerbating drugs to be avoided. Drug doses may have to be altered due to

maternal and physiological changes. RTI and UTI are to be treated aggressively. Be wary of preterm labour. Early decision on anaesthetic options.

Medications Anticholinesterase muscle stimulants Preferred treatment. Reportedly safe in

pregnancy. Eg. Neostigmine, pyridostigmine. Corticosteroids Prednisolone is fairly safe during pregnancy.

Patients who wish to become pregnant are recommended to get pregnant while in steroid-induced remission.

Can lead to PROM.

Medications contd. Immunoglobulin

0.4 g/kg/d IV for 5 consecutive days. Improvement is noticeable in 3-21 days and lasts as long as 3 months.

Antimetabolites

Azathioprine, cyclosporine. Unsafe in pregnancy.

Plasmapheresis Very effective. Consists of 3-6 exchanges of 2-3

L over 1-2 weeks. Can result in premature delivery because of large

hormone shifts. Complications from hypovolemic reactions or

allergies. Expensive.

Surgery Thymectomy done in young patients before preg.

Labour mx. Caesarean: Reserved only for necessary cases. Not depressing respiration is important. Regional anesthesia is good for abdominal

delivery. Epidural: Used to decrease systemic medications

and provide anesthesia for outlet forceps.

Summary Pre pregnancy

• Counselling about risks• Review of therapy• Consider thymectomy

Prenatal

• Joint Obs and Phy care• Continue

Anticholinesterase, steroids and azathioprine

• Plasmapheresis in drug resistant cases

• Fetal surveillance• Avoid stress

Labor/Delivery

• Minimize stress• Continue anticholinesterase

drugs• Steroid cover • Regional analgesia

preferable to narcotics & GA

• Assisted 2nd stage likely• Avoid MgSO4 in

preeclampsia

Postnatal

• Review drug doses• Care and surveillance of

newborn. May need short term anticholinesterase

THANK YOU