Myasthenia gravis: Finding strength in treatment options

Diagnosis

Distinguishing MG from other neuromuscular junction disorders is a pertinent step before treatment. Although the biomarkers discussed in this section are sensitive for making a diagnosis of MG, additional research is needed to classify seronegative patients who do not have circulating autoantibodies that are pathognomonic for MG.¹¹

Scarlett Toruno

Upon clinical examination of observable myasthenic weakness, next steps would require assays for anti-AChR and anti-MuSK.¹ If either of those tests are inconclusive, assays for anti-LRP4 are available (although the LRP4 antibody is also a marker in other neurological disorders).¹²

In the MG diagnostic algorithm, next steps include an electromyography repetitive stimulation test, which, if inconclusive, is followed by single-fiber electromyography.¹ If any of these tests return positive, computed tomography or magnetic resonance imaging is necessary for thymus screening.

What follows this diagnostic schema is pharmacotherapeutic or surgical intervention to reduce, or even eliminate, symptoms of MG.¹

Consensus on treatment standards

A quantitative assessment of best options for treating MG was conducted by leading experts,¹³ who reached consensus that primary outcomes in treating MG are reached when a patient presents without symptoms or limitations on daily activities; or has only slight weakness or fatigue in some muscles.¹³

Dr. Jason Laird

Pyridostigmine, an acetylcholinesterase inhibitor, is recommended as part of the initial treatment plan for MG patients. Pyridostigmine prevents normal breakdown of acetylcholine, thus increasing acetylcholine levels and allowing signal transmission at the neuromuscular junction.¹⁴ Not all patients reach the aforementioned treatment goals when taking pyridostigmine, however; some require corticosteroids or immunosuppressive agents, or both, in addition.

Steroids, such as prednisone and prednisolone, occupy the second line in MG patients because of their ability to produce a rapid response, availability, and economy.^1,15 Initial dosages of these medications are gradually adjusted to a maintenance dosage and schedule, as tolerated, to maintain control of symptoms.¹⁵

In MG patients who are in respiratory crisis, it is recommended that high-dosage prednisone be given in conjunction with plasmapheresis or intravenous immunoglobulin (IVIg).¹⁵ When the response to steroids is inadequate, adverse effects cannot be tolerated, or the patient experiences symptomatic relapse, nonsteroidal immunosuppressive agents are started.

Immunosuppressives are used to weaken the immune response or block production of self-antibodies. Several agents have been identified for use in MG, including azathioprine and mycophenolate mofetil; their use is limited, however, by a lack of supporting evidence from randomized clinical trials or the potential for serious adverse effects.¹³

Referral and specialized treatments. Patients who are refractory to all the aforementioned treatments should be referred to a physician who is expert in the management of MG. At this point, treatment guidelines recommend chronic IVIg infusion or plasmapheresis, which removes complement, cytokines, and antibodies from the blood.¹⁴ Additionally, monoclonal antibody therapies, such as eculizumab, have been shown to have efficacy in severe, refractory AChR antibody–positive generalized MG.¹⁶

Thymectomy has been a mainstay and, sometimes, first-line treatment of MG for nearly 80 years.¹⁵ The thymus has largely been implicated in the immunopathology of AChR-positive MG. Models suggest that increased expression of inflammatory factors causes an imbalance among immune cells, resulting in lymphofollicular hyperplasia or thymoma.¹⁷

Despite the growing body of evidence implicating the thymus in the progression of MG, some patients and physicians are reluctant to proceed with surgical intervention. This could be due to a disparity in surgical treatment options offered by surgeons, and facilities, with varying experience or ability to conduct newer techniques. Minimally invasive approaches, such as video-assisted thoracoscopic surgery and robotic thymectomy, have been found to be superior to traditional open surgical techniques.^18,19 Minimally invasive techniques result in significantly fewer postoperative complications, less blood loss, and shorter length of hospital stay.¹⁹

In addition to the reduced risk offered by newer operative techniques, thymectomy has also been shown to have a beneficial effect by allowing the dosage of prednisone to be reduced in MG patients. In a randomized clinical trial conducted by Wolfe and coworkers,²⁰ thymectomy produced improvement in two endpoints after 3 years in patients with nonthymomatous MG: the Quantitative MG Score and a lower average prednisone dosage. Although thymectomy is not a necessary precursor to remission in MG patients, it is still pertinent in reducing the adverse effects of long-term steroid use – providing objective evidence to support thymectomy as a treatment option.