A 31-year-old primigravida at 39 weeks’ gestation with no prenatal care presented to the labor and delivery unit in active labor. She had been diagnosed with multiple sclerosis (MS) at 28 years of age. She was treated with glatiramer acetate, but discontinued the medication due to flu-like symptoms. Her last relapse was 6 months prior to the pregnancy, at which she was treated with IV methylprednisolone.
The patient requested epidural analgesia for labor pain management. No muscle weakness was detected on neurologic examination. An epidural catheter was placed uneventfully at the L3-L4intervertebral space. No paresthesia was noted during the epidural placement. After a negative test dose, analgesia was successfully obtained with a bolus of 10 mL of 0.125% bupivacaine and 50 mcg of fentanyl, followed by a continuous infusion of 0.0625% bupivacaine and 2 mcg/mL of fentanyl at a rate of 12 mL per hour. She delivered a healthy boy.
The patient was highly encouraged to undergo antenatal assessment and close follow-up during any future pregnancies. She was counseled to stop disease-modifying drugs before conception.
MS is an autoimmune, chronic, inflammatory demyelinating disease affecting the central nervous system. Young adults are most often affected, with the peak onset of symptoms occurring between 20 and 40 years of age. The female-to-male ratio is 2-3:1, meaning the onset of the disease frequently occurs during the childbearing years.1,2
The clinical signs of MS are highly variable, and include visual defects, motor/sensory impairment, gait imbalance, decreased respiratory function, cognitive impairment, and fatigue. Chronic musculoskeletal or neuropathic pain is frequent, and often associated with depression.
The most frequent pattern is relapsing–remitting MS, with exacerbations and partial or full remission periods, eventually advancing to chronic progressive disease. The primary progressive form of MS is less frequent, affecting 10% of patients.1,2
Diagnosis and Treatment
Diagnosis is mainly clinical and supported by MRI that shows multifocal demyelinating plaques in the white matter disseminated in time and space (≥1 lesion in 2 of the following locations: periventricular white matter, juxtacortical white matter, infratentorial region, and spinal cord). Presence of immunoglobulin G oligoclonal bands in the cerebrospinal fluid can confirm the diagnosis.3
There is no curative treatment for MS. Acute exacerbations typically are treated with high-dose IV methylprednisolone. Disease-modifying immunomodulatory agents (eg, interferon beta, glatiramer acetate, ocrelizumab [Ocrevus, Genentech], natalizumab [Tysabri, Biogen], alemtuzumab [Campath, Genzyme], fingolimod [Gilenya, Novartis], etc) reduce the frequency and severity of relapses and slow the progression of the disease.4
MS and Pregnancy
MS is not a risk factor for poor obstetric outcome. The fertility rate and course of pregnancy are not affected by MS.5 Pregnancy does not enhance or accelerate disease progression. On the contrary, similar to other autoimmune diseases, pregnancy can be associated with partial remission. Pregnancy has a protective effect on MS-related inflammatory activity, most likely because of immunomodulated neuroprotective effects of estrogens, significantly decreasing the incidence of relapses, mainly during the third trimester.4,6 The rate of relapses is significantly increased in the postpartum period.
A landmark study by Confavreux et al, on pregnancy in MS (the PRIMS study), included 254 patients with MS during pregnancy and 12 months postpartum, and identified a 30% increased relapse rate in the first 3 months postpartum.7 Postpartum relapse can be triggered by perioperative stress, hyperthermia, infection, etc. Glucocorticoids and immunoglobulins can be used to treat relapses during pregnancy.5 Disease-modifying drugs are discontinued before conception because of their teratogenic effects.4
The degree of neurologic deficit should be assessed and documented carefully. Muscle weakness can result in reduced functional residual capacity, and respiratory function assessment is recommended if restrictive lung diseases are suspected. Supplemental perioperative glucocorticoids should be considered in patients on long-term maintenance therapy. Patients should be counseled about an increased risk for postpartum relapse, regardless of the type of anesthetic administered, if any.
MS and Anesthesia
General anesthesia is considered safe. Patients presenting with dysphagia have an increased risk for pulmonary aspiration, and therefore rapid sequence induction is preferred. However, succinylcholine is best avoided because of the increased risk for hyperkalemia.
Non-depolarizing neuromuscular blocking agent administration is associated with both resistance, due to upregulation of acetylcholine receptors secondary to denervation, and increased sensitivity, due to muscular weakness. Adequate monitoring of neuromuscular block efficacy and reversal is highly recommended, preferably using quantitative techniques, such as electromyography, acceleromyography, etc.
Hyperthermia should be avoided, as it can precipitate relapse by blocking conduction in the demyelinated nerves.1 To avoid hyperthermia, body core temperature should be monitored closely, and active warming devices carefully used during the perianesthetic process.
The data on the safety of neuraxial anesthesia in MS are limited and generated mostly by case reports and nonrandomized observational studies. Historically, neuraxial anesthesia was avoided in patients with MS due to concerns of disease exacerbation caused by the neurotoxic effects of the local anesthetics on demyelinated nerves.1 However, that has changed over time, with more anesthesiologists feeling comfortable performing neuraxial analgesia/anesthesia in parturients with MS.
Drake et al surveyed anesthesiologists in the United Kingdom on their experience and practice patterns in parturients with MS.8 Most responders had limited experience with MS, providing anesthetic care including epidural or spinal blocks in less than 5 patients over the last 10 years, but felt comfortable performing neuraxial anesthesia in parturients with MS.8 Epidural anesthesia during labor can be beneficial in treating pain, thus decreasing peripartum stress.
Spinal anesthesia is achieved by direct intrathecal administration of high-concentration local anesthetics, and can lead to unmasking of silent demyelinated plaques.9 Bader et al linked MS relapse after epidural anesthesia to high concentrations of bupivacaine (>0.25%).10 Therefore, epidural anesthesia with low concentrations of local anesthetic is preferred to avoid toxicity secondary to exposure of the demyelinated fibers in high concentrations of local anesthetics. In a systematic review of management of MS during pregnancy, Bove et al found no effect of anesthesia type on postpartum relapses.11
Peripheral nerve involvement (subclinical polyneuropathy) can occur in patients with MS. Koff et al reported brachial plexopathy after an interscalene nerve block performed under ultrasound guidance in a patient with MS.12
The risk for MS relapse is low during pregnancy, but it increases significantly postpartum. Spinal and epidural anesthesia are not contraindicated in parturients with MS; however, low-concentration, epidurally administered local anesthetics are preferred.
- Nozari A, Bagchi A, Saxena R, et al. Neuromuscular disorders and other genetic disorders. In: Miller RD, ed. Miller’s Anesthesia. Vol 1. 8th ed. New York, NY: Churchill Livingstone; 2015:1266-1286.
- Howard J, Trevick S, Younger DS. Epidemiology of multiple sclerosis. Neurol Clin. 2016;34(4):919-939.
- Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2):292-302.
- Coyle PK. Pregnancy and multiple sclerosis. Neurol Clin. 2012;30(3):877-888.
- Miller DH, Fazekas F, Montalban X, et al. Pregnancy, sex and hormonal factors in multiple sclerosis. Mult Scler. 2014;20(5):527-536.
- Hellwig K, Correale J. Artificial reproductive techniques in multiple sclerosis. Clin Immunol. 2013;149(2):219-224.
- Confavreux C, Hutchinson M, Hours MM, et al. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med. 1998;339(5):285-291.
- Drake E, Drake M, Bird J, et al. Obstetric regional blocks for women with multiple sclerosis: a survey of UK experience. Int J Obstet Anesth. 2006;15(2):115-123.
- Perlas A, Chan VW. Neuraxial anesthesia and multiple sclerosis. Can J Anaesth. 2005;52(5):454-458.
- Bader AM, Hunt CO, Datta S, et al. Anesthesia for the obstetric patient with multiple sclerosis. J Clin Anesth. 1988;1(1):21-24.
- Bove R, Alwan S, Friedman JM, et al. Management of multiple sclerosis during pregnancy and the reproductive years: a systematic review. Obstet Gynecol. 2014;124(6):1157-1168.
- Koff MD, Cohen JA, McIntyre JJ, et al. Severe brachial plexopathy after an ultrasound-guided single-injection nerve block for total shoulder arthroplasty in a patient with multiple sclerosis. Anesthesiology. 2008;108(2):325-328.
David Ermak, DO, is Assistant Professor of Neurology, Department of Neurology; and Sonia Vaida, MD, is Professor of Anesthesiology, Obstetrics, and Gynecology; Vice Chair of Research; and Director of Obstetric Anesthesia, Department of Anesthesiology, at Penn State College of Medicine, Penn State Health Milton S. Hershey Medical Center, in Hershey, Pennsylvania.