Myasthenia gravis: an update for the clinician

Abstract

This paper provides a thorough overview of the current advances in diagnosis and therapy of myasthenia gravis (MG). Nowadays the term 'myasthenia gravis' includes heterogeneous autoimmune diseases, with a postsynaptic defect of neuromuscular transmission as the common feature. Myasthenia gravis should be classified according to the antibody specificity [acetylcholine, muscle-specific receptor tyrosine kinase (MuSK), low-density lipoprotein receptor-related protein 4 (LRP4), seronegative], thymus histology (thymitis, thymoma, atrophy), age at onset (in children; aged less than or more than 50 years) and type of course (ocular or generalized). With optimal treatment, the prognosis is good in terms of daily functions, quality of life and survival. Symptomatic treatment with acetylcholine esterase inhibition is usually combined with immunosuppression. Azathioprine still remains the first choice for long-term immunosuppressive therapy. Alternative immunosuppressive options to azathioprine include cyclosporin, cyclophosphamide, methotrexate, mycophenolate mofetil and tacrolimus. Rituximab is a promising new drug for severe generalized MG. Emerging therapy options include belimumab, eculizumab and the granulocyte- macrophage colony-stimulating factor. One pilot study on etanercept has given disappointing results. For decades, thymectomy has been performed in younger adults to improve non-paraneoplastic MG. However, controlled prospective studies on the suspected benefit of this surgical procedure are still lacking. In acute exacerbations, including myasthenic crisis, intravenous immunoglobulin, plasmapheresis and immunoadsorption are similarly effective.

Keywords: diagnostics; myasthenia gravis; neuroimmunology; therapy/immunotherapy.

Figure 1

Onset of action of the different therapy options in myasthenia gravis. The administration of acetylcholinesterase inhibitors (AChE) improves muscular weakness for several hours, but does not affect the course of the disease. At the beginning of corticosteroid therapy there is the risk of deterioration. Long-term therapy with corticosteroid should be avoided. With the use of immunosuppressive drugs, such as azathioprine, an effect on the myasthenic symptoms starts after several months of therapy. Plasma exchange or the intravenous immunoglobulins (IVIg) are used for myasthenic crisis. Both improve myasthenic weakness for just a few weeks. Thymectomy might influence beneficially the long-term course of non-paraneoplastic myasthenia gravis.