An Adopted 42-Year-Old With Slurred Speech and Memory Loss

Catherine Divingian, MD, PhD; Beena Stanley, MD; Jeffrey Jordan, MD

Disclosures

September 15, 2021

For symptomatic treatment, acetylcholinesterase inhibitors, such as pyridostigmine, may be considered. The mechanism of action involves maintaining acetylcholine in the synaptic cleft by preventing its catabolism by acetylcholinesterase. Acetylcholinesterase inhibitors are more effective in patients with AChR antibody subtypes; they should not be used in those in myasthenic crisis. Adverse effects typically involve muscle hyperactivity, as evidenced by twitching; hyperhidrosis; and gastrointestinal effects, such as diarrhea and flatulence.[7]

Glucocorticoids, such as high-dose prednisone, may be effective in treating patients with MG. The mechanism of action is unknown. This therapy can be useful in cases of myasthenic crisis. Because glucocorticoids can cause immune suppression, hyperglycemia, hypertension, osteoporosis, and other adverse effects, it is vital to assess the patient's clinical presentation before tapering the dosage or starting alternate-day regimens. For patients who are receiving long-term glucocorticoid therapy, dietary adjustments, osteoporosis treatments, vaccinations, and other adjunctive treatments should be considered.[7,8]

Because immune modulation is critical for MG, azathioprine may be a useful treatment option. Most patients respond to this medication, particularly in conjunction with glucocorticoids. Azathioprine is also useful for patients who are unable to tolerate glucocorticoids. The mechanism of action is inhibition of purine synthesis. It is contraindicated in pregnancy and may be associated with an increased risk for tumor development.

Similarly, mycophenolate mofetil, a guanosine inhibitor, may be useful in MG, particularly in reducing the amount of prednisone required for a therapeutic response. However, mycophenolate did not show evidence for clinical improvement compared with placebo in some trials. Adverse effects were mild gastrointestinal symptoms and leukopenia. Cyclosporine suppresses cytokines and calcineurin. This drug seems to reduce the need for prednisone. However, adverse effects are concerning and include nephrotoxicity and hepatotoxicity, elevated blood pressure, and headache. Methotrexate, cyclophosphamide, and rituximab can also be considered for patients with MG.[7,8,9]

Plasma exchange acts rapidly to remove cytokines and autoimmune antibodies. It is recommended for treatment of MG that does not respond to medications, worsening MG that may indicate the need for mechanical ventilation, and myasthenic crisis. Plasma exchange has been shown to have a mortality benefit if it is used at the start of severe symptoms. The onset of action is 1-7 days. Adverse effects that are associated with the use of central venous catheters can be avoided with catheter best practices. Other adverse effects are minor and are usually not indications to discontinue therapy. Hypocalcemia results from citrate binding and can be avoided with calcium supplementation.

IVIG is also a rapid therapy but has a 1- to 2-week onset of action; thus, plasma exchange is considered a first-line treatment. IVIG does have benefit for patients who are not in crisis. Its mechanism of action is most likely multifactorial, but it is thought to work primarily by correcting antibody deficiency and by removing autoantibodies. Adverse effects from IVIG are often related to the rate of infusion and include headache, nausea, shortness of breath, and chills.[6,7,8] However, more serious adverse effects, such as renal impairment and thrombosis, can occur.

Thymectomy is also an integral part of managing MG, especially if a thymoma is found. No evidence supports the procedure in the absence of a tumor. Thymectomy is most effective in patients with the AChR antibody subtype. To optimize outcomes and safety, it is critical to ensure that the patient is not in crisis before the procedure.[7]

Myasthenic crisis is surprisingly common among patients with MG, occurring in up to one fifth of those with the disease. It may be the first time that the patient is known to have MG, which underscores the importance of recognizing the condition when a patient presents with fatigability and respiratory distress, because this will help guide appropriate interventions.[1]

Precipitants of myasthenic crisis include the following:

  • Infection, surgery, and other stressors

  • Drugs, particularly certain antibiotics, beta-blockers, and antiarrhythmics; the crisis often occurs soon after the medication is taken

  • Electrolyte imbalances, especially magnesium

  • Reduction of immunosuppressant dosages

Both patients with thymoma and those who have undergone thymectomy are at risk for myasthenic crisis; thus, removal of the organ does not necessarily correlate with the avoidance of a crisis.[2,10]

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