Immunosuppression (myasthenia gravis/Lambert-Eaton syndrome)

A broad range of therapeutic strategies are available for the treatment of myasthenia gravis (MG). The choice of therapy depends on the severity of the symptoms and the type of antibodies present but the mainstay of treatment in MG involves cholinesterase enzyme inhibitors and immunosuppressive agents.

Symptomatic Treatment: Acetylcholinesterase inhibitors increases the level of acetylcholine at the neuromuscular junction by preventing its enzymatic degradation. Pyridostigmine bromide is preferred over neostigmine because of its longer duration of action. In those with bromide intolerance that leads to gastrointestinal effects, ambenonium chloride can be used. Patients with MuSK MG respond poorly to these drugs and hence may require higher dosages. (1)

Immunosuppressive Treatment: These are indicated in patients who remain symptomatic even after pyridostigmine treatment. Glucocorticoids (prednisone, prednisolone, and methylprednisolone) and azathioprine are the first-line immunosuppressive agents used in the treatment of MG. Second-line agents include cyclosporine, methotrexate, mycophenolate, cyclophosphamide, and tacrolimus. These are used when the patient is unresponsive to treatment, has any contraindication to treatment, or intolerability to the use of first-line agents. Recently, various monoclonal antibodies, including rituximab and eculizumab, have been used to treat drug-resistant MG. (1,3)

Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular junction disorder that may present as a paraneoplastic syndrome or a primary autoimmune disorder. The majority of cases are associated with small-cell lung cancer (SCLC). (2)

In cases where patients continue to have an enduring weakness that does not respond to symptomatic treatments, it becomes necessary to consider immunomodulating or immunosuppressive therapies, some of which are mentioned below.

Intravenous immune globulin (IVIG): IVIG is the primary treatment option for refractory cases. Despite its uncertain mechanism of action, it is believed to function by neutralizing autoantibodies and regulating autoreactive B cells. The usual regimen involves administering 2 g/kg over 2 to 5 days. (3)

Steroids and other immunosuppressive agents: Although azathioprine, mycophenolate, and cyclosporine may be considered for specific cases, their efficacy is generally lower than IVIG. In addition, the potential for significant adverse effects often limits their widespread use. (3)

Rituximab: This monoclonal antibody targets CD20 receptors found on B lymphocytes. Theoretically, it is effective against all B-cell-mediated diseases, including LEMS but data supporting its more extensive utilization is insufficient. (3)

Reference

1. Narayanaswami P, Sanders DB, Wolfe G, et al. International consensus guidance for management of myasthenia gravis: 2020 update. Neurology. 2021 Jan 19;96(3):114-22.
2. Graus F et al. Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes. Neurol Neuroimmunol Neuroinflamm. 2021 Jul;8(4)
3. Pascuzzi RM, Bodkin CL. Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome: New Developments in Diagnosis and Treatment. Neuropsychiatr Dis Treat. 2022;18:3001-3022