The treatment of these two disorders is based on three similar modalities, including symptomatic, immunosuppressive and surgical/chemotherapeutical treatment. First, symptomatic treatments based on the use of anticholineste­rase-inhibitors. Secondly immunosuppressive treatment is used in more severe cases. Thirdly thymectomy for MG or tumor treatment for LEMS is launched apart from the foregoing to make an effort for causal therapy.
Anticholinesterase-inhibitors are first line drugs in MG. Pyridostig­mine are most commonly used up to a daily dose of 720 mg in divided portions with 2-6 hours in between. Pyridostigmine can be obtained in 10 mg, 60 mg or 180 mg retard tablets. The latter may be useful to take in the evening, if patients have severe weakness early in the morning. Nightly doses of pyridostigmine are not indicated. Wakening up to take drugs at night disturbs the sleeping pattern, while rest is an excellent “treatment” for MG. Distigmine is another drug with a prolonged acetylcholinesterase inhibitor effect. Some patients take it to reduce the frequency of drug administration during the day. Other patients feel that it decreases their ability to fine-tune the use of acetylcholinesterase inhibitors. Gastrointestinal side effects like salivation, abdominal cramps and diarrhea, due to the activation of muscarinic acetylcholinereceptors,can be counterac­ted with anticholinergic drugs. Diarrhea also may be treated with loperamide. Pyridostigmine is are fairly well tolerated but the therapeutic effect is moderate.
In LEMS pyridostigmine is used to enhance the effect of 3,4-diaminopyridine, and this seems rational considering the pharmacological action but a recent randomized trial did not demonstrate an additional acute effect after intravenous administration 
3,4-diaminopyrine is the first line drug for the treatment of LEMS [10, 11]. The drug is not officially registered and therefore several formulations are available and locally produced by pharmacologist. In the Netherlands typically capsules of 7.5, 10 or 15 mg are used, as well as 30 or 50 mg retard tablets. The latter are produced by the hospital pharmacy of the Leiden University Medical Center and can be ordered through the pharmacy of the patient. This drug is used in a dose of 10 to maximally 100 mg a day. It is well tolerated, although some patients notice some tingling around the mouth or in the fingers the first half hour after taking the drug. It can enhance gastro-intestinal side effects of pyridostigmin.
Monarsen is an antisense molecule that inhibits the production of acetylcholinesterase and thus has a similar, but more long lasting effect than pyridostigmin. Some small studies in patients suggest a beneficial effect. No large randomized trial has been performed so far 
Steroids are highly effective for the treatment of MG but the notorious side effects form a limiting factor for their use. Usually a start is made with a daily dose of 60-100 mg (1 mg/kg) to be tapered to an alternate day dose which is sufficient to suppress myasthenic symptoms. The final maintenance dosage may vary between 5-60 mg on alternate days for a prolonged period of several years or longer. The effect usually starts after two to three weeks. An unexplained transient initial worsening of myasthenic symptoms may occur within 1 week after starting this therapy in about 10% of the patients and necessitates hospitalization at the start of treatment. If the clinical condition of the pa­tient is brittle there is a substantial hazard of a predniso­ne-induced myasthenic crisis. Steroids may be started in the ambulant situation in patients with pure ocular symptoms without hazard.
To reduce the dose of steroids azathioprine (AZA) may be added to the medication in a dose of 2½-3 mg/kg body weight. This drug is effective after 3-18 months and may eventually lead to a com­plete independence of steroids. Side effects are mild although severe bone marrow depression, liver toxicity, even after years. Furthermore, as in other immunosuppressant there is an increase risk of developing certain malignancies (basal cell skin carcinomas and incidental lymphomas are described). On the other hand teratogenic effects of azathioprine are not obvious 
Ciclosporin is a possible alternative for steroids in a start dose 3- 5 mg/kg body weight. There is now expe­rience with this drug since about 20 years. The effect starts after 2-4 weeks. Intensi­ve monitoring for renal function is highly impor­tant. Further side effects are hypertension, hypertrichosis, headache, tremors, basal cell skin carcinomas and others. Another option is to add a low dose ciclosporin (2 mg/kg) to prednisolon and azathioprine in patients who do not sufficiently respond to this combination. This strategy has not formally been tested in controlled trials.
Mycophenolate-mofetil (MMF) is seen as a promising drug for the treatment of MG or LEMS. A significant improvement may be seen on an average after 12 weeks with a dosage of 2-3 grams (25 mg/kg) a day. In some small series a therapeutic effect is seen in 70% of the patients. Side effects are mainly gastro-intestinal (diarrhea,abdominal pain) or bone marrow depression. Two recent randomized trials in MG failed to show a significant corticosteroid-sparing effect when compared to placebo Muscle Study Group. Neurology.2008, Sanders 2008). This unexpected outcome might have been due a masking of the effect by the steroids, the relative short duration of the trial and the inclusion of a high number of older patients with mild disease. No major side effects of MMF where reported in this study. MMF might be used as a second line treatment to replace AZA if this drug does not induce a significant steroid sparing effect.
Cyclophosphamide and other cytostatic drugs are used but reports on such therapies are scarce. In our hands they appeared highly effective but side effects are considerable.
Plasma-exchange is known as an effective therapy to force an improvement of myasthenic symptoms and is thus used to stop a myasthenic crisis or to turn a chronic treatment resistant myasthenia. Additional immunosuppressive therapy is required as the effect lasts for 3-4 weeks at the utmost. A typical course consists of an exchange one plasma volume 5 times within 2 weeks.
Intravenous administration of immunoglobulins may be equiva­lent to plasma-exchange therapy and studies comparing both therapies are now performed. An infusion of 400 mg/kg body weight a day for 5 consecutive days is recommended or 1 g/ kg 
Most experiences with immunosuppression in neuromuscular junction disorders are from patients with AChR myasthenia gravis. There is no reason to assume that seronegative myasthenia patients do react otherwise.
Thymectomy generally is recognized as an effective therapy for MG. Antibody titer decrease concurs with clinical improvement after thymectomy . Nevertheless there is no common opinion about the indica­tion for this operation in different situations . There is divergence of opinion about restrictions with respect to age of onset of MG, the question whether patients with ocular MG should be operated upon or not, the surgical technique (trans­sternal, cervical or a combined approach; video assisted transcervical surgery, or video assisted robotic surgery) and the question if the use of immunomodulatory drugs should be preferred over an operation.
We advocate a thymectomy in all pa­tients with a thymoma and all patients with generalized MG in whom the disease became manifest before the age of 50 years although we can’t be sure about the real effect of this operation. Thymectomy always is an elective intervention and never should be performed in case of an increased operation risk. The effect of the operation may last 6 months to about 3 years. In our experience about 25% of the patients do not benefit from the operation while more than 40% go into a remission.
Tumor treatment in LEMS. In 50% of the patients with LEMS a small cell lung cancer is detected. The first line treatment is chemotherapy. This also has a beneficial effect on the clinical manifestations of the LEMS. Thus, in most patients weakness and autonomic symptoms improve during chemotherapy. A long term remission of the neuromuscular disease can follow, if the tumor is successfully treated, with minimal or even no need for symptomatic treatment with 3,4-diaminopyridine.
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