Myasthenia gravis (MG),
Lambert-Eaton myasthenic syndrome (LEMS) and
neuromyotonia are
neuromuscular transmission disorders occurring with or without associated
malignancy. Due to the common antibody-mediated pathophysiology, immunosuppression has an important role in the treatment of each of these disorders. Symptomatic treatment is more variable.
Pyridostigmine is first-line treatment in generalized MG. Response seems to be better in patients with
acetylcholine receptor (AChR)
antibodies than in patients with
antibodies against muscle-specific
tyrosine kinase (
MuSK).
Pyridostigmine can be sufficient in mild MG, although most patients need additional immunosuppressive therapy. If so,
prednisolone is efficient in the majority of the patients, with a relatively early onset of clinical effect. High
drug dosage and
treatment duration should be limited as much as possible because of serious
corticosteroid-related side effects. As long-term treatment is needed in most patients for sustainable remission, adding non-
steroid immunosuppressive drugs should be considered. Their therapeutic response is usually delayed and often takes a period of several months. In the meantime,
corticosteroids are continued and doses are tapered down over a period of several months. There are no trials comparing different immunosuppressive drugs. Choice is mainly based on the clinician's familiarity with certain drugs and their side effects, combined with patients' characteristics. Most commonly used is
azathioprine. Alternatively,
tacrolimus,
cyclosporine A,
mycophenolate mofetil or
rituximab can be used. The use of
cyclophosphamide is limited to refractory cases, due to serious side effects.
Plasma exchange and
intravenous immunoglobulin induce rapid but temporary improvement, and are reserved for severe disease exacerbations because of high costs of treatment. It is recommended that computed tomography (CT) of the thorax is performed in every AChR-positive MG patient, and that patients are referred for
thymectomy in case of
thymoma. In patients without
thymoma,
thymectomy can be considered as well, especially in younger, AChR-positive patients with severe disease. However, definite proof of benefit is lacking and an international randomized trial to clarify this topic is currently ongoing. When LEMS is suspected, always search for
malignancy, especially
small cell lung carcinoma with continued screening up to two years. In paraneoplastic LEMS,
cancer treatment usually results in clinical improvement of the myasthenic symptoms.
3,4-Diaminopyridine is first-line symptomatic treatment in LEMS. It is usually well tolerated and effective. When immunosuppressive therapy is needed, the same considerations apply to LEMS as described for MG. Peripheral nerve hyperexcitability in
neuromyotonia can be treated with
anticonvulsant drugs such as
phenytoin,
valproic acid or
carbamazepine. When response in insufficient, start
prednisolone in mild disease and consider the addition of
azathioprine.
Plasma exchange or
intravenous immunoglobulin is indicated in severe
neuromyotonia and in patients with
neuromyotonia combined with central nervous system symptoms, a clinical picture known as Morvan's syndrome.