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INTRODUCTION

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Acquired, autoimmune myasthenia gravis (MG), the most common noniatrogenic disorder of neuromuscular transmission (DNMT), remains the favorite child of many neuromuscular clinicians. Arguably, it provides more professional satisfaction than any other neuromuscular disease. This fulfillment is derived in part from the intellectual satisfaction that comes from understanding disease pathogenesis. At the same time, satisfaction is gained by the ability to make meaningful improvements in patient function and quality of life through the application of rational and effective treatment. MG represents one of medicine's most notable translational successes in bringing basic science to the bedside.

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Although descriptions of individuals likely to have been affected by MG can be traced to antiquity, our current understanding of disease mechanism(s) originates from a series of seminal observations and discoveries. Thomas Willis, a seventeenth-century physiologist, is frequently credited for initially describing the clinical syndrome of MG. The concept of MG as a DNMT and the first therapeutic triumph are often credited to British clinician Mary Walker. She described the benefits of cholinesterase inhibitors in the 1930s; her discovery extrapolated from her observations related to the similarities between MG and curare toxicity. In 1960, Simpson first promoted the hypothesis of an autoimmune basis for MG on the basis of his observations of an increased prevalence in young women and in individuals with other autoimmune diseases.1 In that same decade, support for MG as a DNMT was provided by the in vitro electrophysiological demonstration that miniature end plate potential (EPP) amplitudes in MG were greatly reduced.2 In 1973 Daniel Drachman et al. solidified the concept of MG as a postsynaptic DNMT by demonstrating loss of acetylcholine receptors (AChR) in MG patients through α-bungarotoxin labeling techniques.3 In the same year, Patrick and Lindstrom confirmed the autoimmune nature of MG with the development of an experimental MG model in rabbits who became weak when immunized with AChR.4 In 1976, the seminal article describing the value of AChR autoantibody testing in the diagnosis of myasthenia was published.5 In 2001, Hoch et al. first reported the association between MG and autoantibodies directed against muscle-specific kinase (MuSK).6 In 2008, unnamed autoantibodies directed at clustered AChRs were found in low titer in the serum of approximately two-thirds of AChR and MuSK seronegative patients.7,8 In 2011, patient's with autoantibodies directed at the lipoprotein receptor protein 4 (LPR4) were identified as a third MG serotype.9

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Historically, seronegative MG referred to patients lacking AChR autoantibodies. With the discovery of MuSK autoantibodies, the concept of double seronegative MG patients was coined. As our knowledge of LPR4 MG is somewhat limited, and as LPR4 autoantibody tests are not commercially available at the time of writing this, seropositive will be used in this chapter to refer only to AChR and MuSK MG.

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The incidence of MG and its serodistribution may vary with geography and/or ethnicity.10 MG has been estimated to ...

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