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Abstract: This update covers several articles on diagnosis and misdiagnosis of myasthenia gravis (MG), the role of complement in MG, and then an impressive number of recent treatment trials. There is a negative study on any corticosteroid-sparing effect of intravenous immunoglobulin. A number of positive studies are reviewed. Open-label extension studies of phase 3 trials showed benefit regarding quality of life with efgartigimod and in functional measures with ravulizumab. The phase 3 RAISE trial of zilucoplan, a self-administered complement C5 inhibitor, is covered as well as the MyCarinG trial of rozanolixizumab. The notion of using fast-acting therapies early in the course of MG is addressed. The last sections center on MG and Lambert-Eaton myasthenic syndrome as a consequence of immune checkpoint inhibitor therapy., Competing Interests: The author reports no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: This update covers a number of treatment topics starting with Fc receptor inhibitors and the Federal Drug Administration approval of efgartigimod. Some uncertainties regarding the use of corticosteroids are addressed, namely the risk of exacerbation with initiation of treatment and how to taper. The presence and potential importance of antibody overshoot following plasmapheresis is noted and the evolving increase in usefulness of acetylcholine receptor antibodies in diagnosing ocular myasthenia. Several recent series and case reports regarding coronavirus 2019 and myasthenia gravis are reviewed. The topics of myasthenia gravis and pregnancy, and another look at thymectomy in MG are provided. Finally, a couple of case reports on Lambert-Eaton myasthenic syndrome concentrate on the ice pack test and an autoantibody association with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome in the same patient., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Myasthenia gravis associated with concurrent inflammatory myopathy is a rare but well-described syndrome, most often seen in patients with thymoma. We present a case of biopsy-proven granulomatous myositis associated with positive acetylcholine receptor binding, blocking, and modulating and antistriated antibodies, without clear clinical symptoms of myasthenia gravis and in the absence of thymoma. In addition, we include rarely reported neuromuscular ultrasound findings of granulomatous myositis in a patient without sarcoidosis. Inflammatory myopathy may precede development of myasthenia gravis in myasthenia gravis associated with concurrent inflammatory myopathy, and it is important to remain vigilant for symptoms suggestive of myasthenia gravis, especially in the presence of positive myasthenia-associated antibodies., Competing Interests: D. Lacomis receives ongoing royalties from UpToDate. The other authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: This update covers recommendations for myasthenia gravis (MG) in patients with coronavirus 2019 disease as well as reports of the clinical features of patients with MG and coronavirus 2019. Updated advisory committee recommendations for the use of thymectomy in generalized MG are also provided. Other MG topics include lipoprotein receptor-4 and agrin antibody associations, factors influencing conversion of ocular to generalized MG, the use of rituximab for more recent onset disease, immunoglobulins for maintenance therapy, and fatigue and depression., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Cancer immunotherapy has transformed the field of oncology and enabled more effective management of previously refractory neoplasms by activation of the immune response. Upregulation of the immune response may also trigger autoimmune adverse events, including neuromuscular complications. We performed a systematic review of autoimmune neuromuscular complications following immune checkpoint blockade. We searched PubMed database and identified 81 cases described, including 30 cases of myasthenia gravis (MG), 29 cases of neuropathy and 22 cases of myopathy. Most patients (89%) developed neuromuscular complications within 3 months from starting immune checkpoint blockade and 40% of all patients had elevated serum CK>1000 IU/L (typical normal <200). Guillain-Barre syndrome variants and overlaps of MG with myositis and/or myocarditis also occurred. One quarter of myasthenia patients presented with exacerbations of previously diagnosed myasthenia gravis, while neuropathy and myopathy typically presented with a new onset. Most patients improved with immunomodulatory treatment, but neuromuscular complications were sometimes refractory and associated with high mortality of 26% from cancer recurrence, comorbidities, or treatment complications. Poor outcomes were more common with exacerbations of pre-existing myasthenia gravis and myocarditis overlap. Future prospective studies are needed to elucidate mechanisms and risk factors for autoimmune adverse events following immune checkpoint blockade., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This update begins with myasthenia gravis and the roles of anti-agrin and cortactin antibodies. Regarding diagnosis, a report on repeated ice pack testing is highlighted as are several reports on the close correlation of electrodiagnostic testing with clinical features and the response to treatment. The incidence of head drop and associated clinical and ventilatory features are gleaned from a retrospective study. We also discuss a study that assessed the predominantly symmetric and conjugate ocular findings in MuSK-myasthenia gravis. Other topics that are covered include quality of life and preoperative risk. We then summarize the positive treatment trials of subcutaneous immunoglobulin and eculizumab. Turning to Lambert-Eaton Myasthenic Syndrome, we report on an epidemiologic study performed on the veteran affairs population, the results of the DAPPER study of 3, 4 diaminopyridine, and look to the future for other treatment options involving calcium gating modifiers.

An increasing incidence of myasthenia gravis (MG) has been reported in the elderly, but the full clinical ramifications of late-onset myasthenia gravis (LOMG) remain unclear. We describe the clinical features of our cohort of patients with MG with an emphasis on an onset after the age of 50. This was a retrospective analysis of medical records of a cohort of patients followed in two tertiary neuromuscular clinics and comparison of early onset MG (EOMG) versus LOMG. There were 174 patients with a mean age of onset of 55.2 ± 19.1 years, and 44 % were women. Late onset of myasthenia gravis after age 50 was reported in 114 patients (66 %). Anti-AChR antibody titers were elevated in 78 % of patients (65 % with EOMG vs. 85 % with LOMG; p = 0.003), and frequency of elevated titers of anti-MuSK antibodies was similar in both groups (present in 38 % of all tested seronegative patients). Myasthenic crisis was equally common in generalized EOMG and LOMG (13 %). Ocular MG was more common in LOMG compared to EOMG (40 vs. 18 %, p = 0.021). Diabetes was more prevalent with LOMG (27 vs. 5 %; p = 0.0002). Overlapping clinical features of EOMG and LOMG are consistent with a continuous clinical spectrum of a single condition, with more frequent occurrence of seropositive and ocular MG with a late onset. A higher burden of comorbidities, such as diabetes mellitus, may warrant a modified approach to treatment of myasthenia in LOMG. However, overall disease severity may not be higher with aging. These observations have implications for design of MG clinical trials and outcomes studies.

Myasthenic crisis is a serious occurrence, affecting up to 27% of patients with myasthenia gravis. In the approach to the patient with myasthenic crisis, (1) the diagnosis of myasthenia gravis is confirmed; (2) respiratory failure is evaluated and treated in the intensive care unit, while potential precipitating factors are identified and managed; (3) immunomodulatory treatment is initiated; and (4) complications are avoided or managed promptly. The mortality rate should be 5% or less, with the elderly being most vulnerable.