A Practical Approach to Managing Patients With Myasthenia Gravis—Opinions and a Review of the Literature

Abstract

When the diagnosis of myasthenia gravis (MG) has been secured, the aim of management should be prompt symptom control and the induction of remission or minimal manifestations. Symptom control, with acetylcholinesterase inhibitors such as pyridostigmine, is commonly employed. This may be sufficient in mild disease. There is no single universally accepted treatment regimen. Corticosteroids are the mainstay of immunosuppressive treatment in patients with more than mild MG to induce remission. Immunosuppressive therapies, such as azathioprine are prescribed in addition to but sometimes instead of corticosteroids when background comorbidities preclude or restrict the use of steroids. Rituximab has a role in refractory MG, while plasmapheresis and immunoglobulin therapy are commonly prescribed to treat MG crisis and in some cases of refractory MG. Data from the MGTX trial showed clear evidence that thymectomy is beneficial in patients with acetylcholine receptor (AChR) antibody positive generalized MG, up to the age of 65 years. Minimally invasive thymectomy surgery including robotic-assisted thymectomy surgery has further revolutionized thymectomy and the management of MG. Ocular MG is not life-threatening but can be significantly disabling when diplopia is persistent. There is evidence to support early treatment with corticosteroids when ocular motility is abnormal and fails to respond to symptomatic treatment. Treatment needs to be individualized in the older age-group depending on specific comorbidities. In the younger age-groups, particularly in women, consideration must be given to the potential teratogenicity of certain therapies. Novel therapies are being developed and trialed, including ones that inhibit complement-induced immunological pathways or interfere with antibody-recycling pathways. Fatigue is common in MG and should be duly identified from fatigable weakness and managed with a combination of physical therapy with or without psychological support. MG patients may also develop dysfunctional breathing and the necessary respiratory physiotherapy techniques need to be implemented to alleviate the patient's symptoms of dyspnoea. In this review, we discuss various facets of myasthenia management in adults with ocular Farrugia and Goodfellow Practical Approaches to Myasthenia Management and generalized disease, including some practical approaches and our personal opinions based on our experience.

Controversies in Ocular Myasthenia Gravis

“…Oral treatment with prednisone or prednisolone is first-choice immunosuppression in patients with disabling OMG. Treatment can be started at full dosage or with an escalating regimen, but maximum doses (25-50 mg/day) are generally lower than in GMG (83,89,90). Once symptom control has been achieved, prednisone is slowly tapered to the lowest effective dose or withdrawal.…”

“…This finding deserves confirmation in further studies. Steroid-sparing agents are frequently used in long-term therapy, with the same criteria and treatment regimens as in GMG (89,90). In uncontrolled studies, azathioprine (85), mycophenolate mofetil (19,93), and tacrolimus (94) were beneficial both in relieving symptoms and in preventing disease progression.…”

“…In a RCT, no response to intravenous immunoglobulin was detected in a small OMG population (97). B cell depletion with rituximab, a chimeric anti-CD20 monoclonal Ab, has gained increasing popularity in the treatment of GMG (4,90,98). Rituximab was very effective in the few OMG subjects treated so far (99,100) and, although evidence is scarce, may be considered in refractory disease.…”

“…Supportive measures as crutch glasses for severe ptosis and prisms in patients with diplopia are helpful in treatmentresistant OMG. Ptosis surgical correction is effective and well-tolerated when exposure keratitis is avoided (90,111); the possibility of diplopia worsening should be discussed beforehand. Topical naphazoline, a mainly α2-agonist, was found to be effective in relieving mild to moderate ptosis (112).…”

Immunopathology of Autoimmune Myasthenia Gravis: Implications for Improved Testing Algorithms and Treatment Strategies

“…Accurate antibodies detection is crucial for diagnosis and prognosis, together with other factors, such as thymus histology, age and clinical features. For instance, AChR antibody-positive patients tend to have follicular hyperplasia of the thymus and practically all cases of thymoma are AChRAbs positive, thus thymectomy (surgical removal of thymus) is a first-line treatment choice in AChR MG, excluding patients with only OMG ( 29 , 92 – 94 ). In addition, refractory AChR-MG is usually present in patients with thymoma.…”