In patients with acetylcholine receptor (AChR) antibody–positive myasthenia gravis, circulating antibodies bind to the AChRs, which may block acetylcholine binding, lead to crosslinking of receptors promoting internalization and degradation, and induce postsynaptic membrane damage via complement activation. The number and availability of receptors are reduced such that end-plate potentials are insufficient to generate action potentials in a number of muscle fibers, causing weakness.

Orbicularis oculi weakness may be indicated by a positive peek sign after gentle eyelid closure. After complete initial apposition of the lid margins, they quickly (within 30 seconds) start to separate and the sclera starts to show (ie, a positive peek sign). The presence of a peek sign increases the likelihood of myasthenia gravis (likelihood ratio, 30.0; 95% confidence interval, 3.2-278.0), but absence of the peek sign does not rule it out.

Intravenous immunoglobulin (IVIG) modulates multiple immunologic events (blue boxes) involved in the pathogenesis of autoimmune neuromuscular diseases. Diseases for which specific therapeutic actions of IVIG are supported by experimental evidence are listed in each box. In autoimmune neuromuscular diseases, an antigen, through molecular mimicry, defective clonal deletion, or other mechanisms, triggers an immune response that results in loss of immune tolerance to self-antigens. Infused IVIG interferes with costimulatory molecules involved in antigen presentation and modulates subsequent immunologic events. These events, mediated by activation of B cells with production of autoantibodies and by T cells, lead to tissue damage via complement activation, macrophage–Fc receptor interaction, and cytotoxic T cells. Other possible therapeutic actions of IVIG not shown in this illustration include increased catabolism of IgG, alteration of effector functions of T cells, and modulation of apoptosis. CIDP indicates chronic inflammatory demyelinating polyneuropathy; DM, dermatomyositis; GBS, Guillain-Barré syndrome; ICAM-1, intercellular adhesion molecule 1; IFN-, interferon ; IL, interleukin; LEMS, Lambert-Eaton myasthenic syndrome; MAC, membrane attack complex; MG, myasthenia gravis; MMP, matrix metalloproteinase; NO, nitric oxide; PM, polymyositis; SPS, stiff-person syndrome; TGF-, transforming growth factor ; TNF-, tumor necrosis factor ; VCAM-1, vascular cell adhesion molecule 1.