Multiple Sclerosis

MS is a progressive, inflammatory, and demyelinating disease with periods of remissions and exacerbations that can be triggered by infection, stress, and increased temperature. The baseline treatment of MS is immunomodulatory disease-modifying therapies (DMTs) such as interferon, glatiramer acetate, mitoxantrone, and natalizumab, which are all avoided in pregnancy. MS relapses during pregnancy are treated with steroids, which are regarded as safe.¹ Patients with MS typically have fewer exacerbations during pregnancy, but the risk of relapse is increased in the first 3 months postpartum.^{2, 3}

Anesthesiologists must assess patients with MS for neurologic deficits, including muscle, respiratory, and diaphragmatic weakness, and inability to cough or handle secretions. It is prudent to document all preoperative neurologic deficits. If respiratory weakness is present, pulmonary function tests (PFTs) should be obtained. Patients with MS can have autonomic system involvement, manifesting as hemodynamic instability. Anesthesiologists should be aware of patients’ recent steroid use because stress-dose steroids may be indicated.

Hyperthermia is a known trigger for MS exacerbations. Labor rooms should be kept at appropriate temperatures, and maternal fever should be treated aggressively with cooling blankets and acetaminophen.

The type of anesthesia chosen for MS patients is not thought to increase exacerbations.^{3, 4} The PRIMS study,³ which was large and prospective, clearly demonstrated that epidural anesthesia did not have an effect on disability nor MS relapse rate postpartum. Spinal anesthesia has been implicated, however, in increasing the risk of exacerbation possibly due to a high concentration of local anesthetic that may be neurotoxic when placed near already demyelinated CNS tissue.⁴ In patients with MS presenting for cesarean delivery, spinal anesthesia can be easily replaced with epidural anesthesia. Still, the safe use of spinal anesthesia has been reported.⁵

A survey of 592 obstetric anesthesiologists in the United Kingdom revealed that 84 percent would use spinal anesthesia for elective cesarean delivery, and 90 percent would use spinal anesthesia for emergency cesarean delivery. This survey, unfortunately, was not designed to report clinical outcomes.⁶ Lu et al.⁷ examined the use of obstetric neuraxial anesthesia in patients with MS compared with the general population and did not find a difference in disability in patients with or without epidural or spinal anesthesia.

Choosing the appropriate anesthetic technique for a patient with MS is challenging because there are no randomized, controlled trials to guide management. Some anesthesiologists may prefer to avoid neuraxial anesthesia altogether and use general anesthesia for patients with MS, but this is only applicable to surgical procedures. For labor pain, an epidural certainly provides better pain relief than systemic medication. Therefore, if time permits, a thorough discussion with the patient about the risks and benefits of the different types of analgesia and anesthesia is recommended, and it is prudent to ensure that the patient understands that the risk of MS relapse exists regardless of the type of anesthesia used.

If general anesthesia is chosen for a patient with MS, caution must be taken when using neuromuscular blocking drugs. As with patients with any chronic motor weakness, patients with MS can have increased numbers of extrajunctional acetylcholine receptors secondary to denervation or disuse. Hence succinylcholine use may cause hyperkalemia from increased muscle release of potassium. Additionally, the increased acetylcholine receptors can decrease the sensitivity to nondepolarizing neuromuscular blocking drugs.⁸

Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune disorder in which autoantibodies are formed against the postsynaptic nicotinic acetylcholine receptor (nAChR) at the neuromuscular junction. A decreased number of nAChRs results in skeletal muscle weakness. The muscle groups usually affected are the ocular, bulbar, and proximal limb muscles. MG is progressive with relapses and periods of remission. The course of MG is unpredictable during pregnancy. Stress, pain, infection, fever, surgery, inflammation, and hypothyroidism are associated with MG relapses or crises and can occur with pregnancy and labor.^{9, 10} Myasthenic crisis is the extreme weakness of bulbar or respiratory muscles resulting in airway obstruction or respiratory failure and the need for mechanical ventilation.

Medical treatment of MG involves anticholinesterases and steroids. Patients refractory to medication often require plasmapheresis and may require thymectomy. Anticholinesterases, most commonly pyridostigmine, must be continued throughout pregnancy and on the day of delivery to prevent MG relapses.^{9, 10}

Cholinergic crisis, usually due to excess anticholinesterase medication, may be seen rarely in pregnancy due to pharmacokinetic changes. The symptoms are salivation, sweating, miosis, diarrhea, vomiting, lacrimation, bradycardia, bronchospasm, muscle weakness, and respiratory failure.^{9, 10} Anesthesiologists must be aware that myasthenic and cholinergic crisis can both present with muscle weakness and respiratory compromise, and immediate respiratory support and treatment are usually needed.

Preanesthetic evaluation of patients with MG should include a full assessment of symptoms, location, and weakness. Medication doses and frequency should be known, and anticholinesterases should be continued on the day of delivery and administered intravenously if oral absorption is questionable. Patients with respiratory compromise should have PFTs to assess the baseline degree of weakness and to predict the need for postoperative mechanical ventilation, should general anesthesia be needed. All patients should be counseled that mechanical ventilation and intensive care might be indicated if a myasthenic crisis develops.

Vaginal delivery is preferred in patients with MG because surgery itself is a risk factor for MG crisis. Neuraxial anesthesia (epidural, spinal, and CSE) has been safely used in patients with MG both for labor analgesia and for surgical anesthesia. Labor epidurals are preferred to avoid the respiratory depressive effects of systemic opioids and should be initiated early in labor to prevent pain and fatigue, which may precipitate a MG crisis. Anesthesiologists should closely monitor MG patients with labor epidurals for respiratory or bulbar compromise. Spread of labor analgesia should be limited to T10 to prevent any respiratory muscle weakness.¹,¹¹

The lowest effective concentration of local anesthetic should be used for labor analgesia infusions to minimize motor block. Patients with MG may have weakness of the pelvic and abdominal muscles and may require an assisted second stage of labor with forceps or vacuum. Ester local anesthetics should be avoided because anticholinesterases impair their degradation. If a cesarean delivery is indicated, neuraxial anesthesia is preferred to avoid prolonged mechanical ventilation following general anesthesia, but the T4 block needed may cause unsustainable respiratory compromise in MG patients with severe bulbar and respiratory symptoms at baseline.¹²

If general anesthesia is needed for cesarean delivery, neuromuscular antagonists should be avoided or used with caution. With a decreased number of nAChRs, the patient with MG is less sensitive to succinylcholine because the presence of receptors is necessary for the action of the drug, but a higher dose of succinylcholine can cause a prolonged block due to anticholinesterase activity or phase II block. Conversely, MG patients are more sensitive to nondepolarizing neuromuscular antagonists because fewer nAChRs results in a greater percentage of antagonized receptors per dose.

Medications that can exacerbate respiratory depression such as opioids and sedatives should be avoided. Certain antibiotics such as aminoglycosides can worsen muscle weakness. Magnesium is contraindicated in patients with MG because it inhibits the release of acetylcholine at the neuromuscular junction and decreases the postsynaptic response to ACh. Patients with MG who need seizure prophylaxis may receive phenobarbital instead.^{9, 10}

Maternal anti-nAChR antibodies can cross the placenta, resulting in neonatal MG. Poor tone and weak cry in the newborn are suggestive of this. Neonatal MG may require immediate respiratory support.^{9, 10, 12}