Myasthenia gravis is an autoimmune disease affecting the neuromuscular junction, at which circulating antibodies compete with acetylcholine, interfering with neuromuscular transmission and causing skeletal muscle weakness. It has an incidence of around 1 per 100,000 and is more common in females, with an onset at any age. The muscles that are most commonly involved are the oculomotor, facial, pharyngeal and respiratory. The weakness is generally made worse by stress, physical exertion, minor infections and fatigue and is improved by rest.
The disease is treated with acetylcholinesterase inhibitor therapy. The treatment of choice is pyridostigmine in a dose range of 30-90 mg orally given at regular intervals through the day. The side effects of treatment may include bradycardia, sweating and increased salivary secretion.
Problems and special considerations
Pregnancy has a variable effect on the disease, with roughly similar proportions of women showing improvement, deterioration or no change in clinical condition. The increased volume of distribution in pregnant women and altered renal clearance of drugs may cause aggravation of symptoms in some women, and dose modification may be required.
As with many neurological diseases, women with myasthenia gravis may be very worried about regional analgesia and anaesthesia and any adverse effect on their disease.
During labour, an increase in weakness can be expected, which may cause a marked reduction in maternal expulsive efforts in advanced labour and an increased need for instrumental delivery. Parturients with severe disease are also at risk of respiratory insufficiency and aspiration of gastric contents, which may increase as labour progresses.
Requirements for acetylcholinesterase inhibitors may be difficult to estimate during labour because of worsening weakness and possibly reduced gastric absorption of oral pyridostigmine (especially if opioids have been administered). Inadequate dosage may lead to severe weakness (myasthenic crisis), whereas overdosage with acetylcholinesterase inhibitors may lead to a cholinergic crisis (muscle weakness and fasciculation, sweating, miosis, lacrimation, abdominal colic, etc.).
There is increased sensitivity to non-depolarising neuromuscular blocking drugs, with the risk of prolonged neuromuscular blockade during and after general anaesthesia. Resistance to suxamethonium has been reported, although most authorities recommend a normal dose. Magnesium sulfate worsens muscle weakness and is not recommended for the prophylaxis of eclampsia in these patients. It may be used for the treatment of an eclamptic seizure, although caution must be exercised and the need for respiratory support must be anticipated.
Table 130.1 Oraland parenteralanticholinesterase inhibitors (all the following dosages are equivalent in clinical effect)
|
Neostigmine |
15 mg oral 0.7-1.0 mg intramuscular 0.5 mg intravenous |
|
Pyridostigmine |
60 mg oral 3-4 mg intramuscular 2 mg intravenous |
Some women will be taking long-term steroid therapy and will require supplementation in labour.
Placental transfer of maternal antibodies may cause neonatal myasthenia.
Management options
There should be a team approach to the management of a woman with myasthenia gravis during the antenatal period. The extent of her muscle weakness, and whether this affects the bulbar and respiratory muscles, should be carefully assessed, and the disease should be regularly monitored during the pregnancy.
Treatment will need to be adjusted to maintain muscle strength, and pulmonary function tests may be useful in assessing the strength of the respiratory muscles. Although vaginal delivery is preferred in this patient group, the mode of delivery should be decided on obstetric grounds, taking into account the severity of the illness and the ability of the woman to tolerate the work of labour.
Regional analgesia is advisable, to minimise the stress of labour and to avoid the sedative effects of pethidine or Entonox. If opioids have not been given, gastric function can be considered to be near-normal and oral medication continued. If in doubt in severe cases, equivalent doses of parenteral acetylcholinesterase inhibitors can be given (Table 130.1). Atropine should also be given to reduce unwanted cholinergic effects. If in doubt over whether worsening weakness represents a myasthenic or cholinergic crisis, edrophonium 2 mg intravenously will improve the former but worsen or have no effect on the latter.
In well-controlled myasthenia gravis, caesarean section may be performed under regional anaesthesia. If the disease is not well controlled, the risk of aspiration and respiratory impairment with a high regional block must be weighed against the risks of respiratory impairment following general anaesthesia. Non-depolarising neuromuscular blocking drugs are usually not necessary, but if one is required the dose should be significantly reduced and neuromuscular monitoring should be used to confirm adequate recovery before extubation. Following general anaesthesia, some mothers may require postoperative ventilation while their medication is reintroduced and their muscle power returns to normal.
Key points
• Team management and advance planning are essential for the pregnant woman with myasthenia gravis.
• Regular monitoring of muscle strength throughout pregnancy is essential.
• Oral medication can be continued throughout labour unless the disease is very severe and gastric function is in doubt, when parenteral medication may be substituted.
• Both myasthenic and cholinergic crises may occur.
• Regional analgesia and anaesthesia are indicated in most cases.
Further reading
Gilhus NE. Myasthenia gravis. N Engl J Med 2016; 375: 2570-81.
Norwood F, Dhanjal M, Hill M, et al. Myasthenia in pregnancy: best practice guidelines from a U.K. multispecialty working group. J Neurol Neurosurg Psychiatry 2014; 85: 538-43.
Sussman J, Farrugia ME, Maddison P, et al. Myasthenia gravis: Association of British Neurologists’ management guidelines. Pract Neurol 2015; 15: 199-206.