Pyridostigmine (Mestinon) is useful in treating the symptoms of MG. It acts by boosting the signal between nerve and muscle, thereby enhancing the ability of the nerve to communicate with muscle and to improve muscle strength. It is important to understand that pyridostigmine does not affect the underlying abnormal immune response that causes MG. Instead, it provides symptomatic relief. A useful analogy is to think of pyridostigmine for MG in the same way as one thinks about Tylenol for a headache Tylenol may alleviate the symptom of headache without fixing the underlying cause of the headache. It is important to recognize that pyridostigmine need only be taken when symptoms of MG are present or anticipated. If you don't have any symptoms then there is no need to take pyridostigmine.
Abdominal cramps, bloating and diarrhea are common side effects of pyridostigmine. If you develop these side effects but still wish to take pyridostigmine because it helps your symptoms, then you should talk to your neurologist about taking another medication such as hyoscyamine, to help alleviate these side effects.
Pyridostigmine is often the first line of treatment offered to patients with MG. Occasionally it may be sufficient for those with ocular MG, but patients with generalized MG typically need some treatment that addresses the underlying abnormal immune response (see About MG). These treatments are often referred to as immune suppressive or immune modulating.
Prednisone belongs to a class of medicines known as steroids. Prednisone is believed to be an excellent treatment for patients with MG, but it has the potential to cause many side effects. There are, therefore, both pros and cons to taking prednisone. On the positive side, prednisone is an oral medication (may be taken daily or every other day), works quite quickly (typically over a period of weeks to months) and continues to exert a beneficial effect for as long as it is taken. Unlike pyridostigmine that can be taken as needed based on the occurrence of symptoms, prednisone needs to be taken regularly in order to receive benefit. The downside to prednisone, as noted before, is that it may cause side effects that include increased appetite, weight gain, difficulty sleeping, irritability, diabetes, osteoporosis (thinning of the bones), cataracts, glaucoma and hypertension. Since prednisone acts by suppressing or altering the immune system, people taking prednisone are also at an increased risk for developing infections. It is easy to be frightened by this long list of potential side effects, but it is important to recognize that not everyone experiences side effects and the risk of developing a side effect is heavily influenced by dose the lower the dose, the lesser the likelihood that side effects will occur. If you do decide to take prednisone, you should discuss with your physician measures that you can take to minimize the risk of developing side effects and to monitor for their occurrence.
Azathioprine (Imuran) is an immune suppressive medication that is sometimes also described as a "steroid-sparing agent". There is a long history of using azathioprine to treat MG and it is generally a safe and well-tolerated medication. The downside to Azathioprine is that it may take many months (perhaps as long as a year or even 18 months) to fully take effect. Azathioprine is often used in conjunction with prednisone – prednisone for the short-term effects and azathioprine for the long-term effects. The goal of treatment with Azathioprine is to maintain control of MG symptoms while permitting a gradual reduction in the dose of prednisone. While taking Azathioprine, it is important to have regular monitoring for side effects in the form of a blood count and measurement of liver enzymes.
Mycophenolate (CellCept) is an immune suppressive medication that affects the immune system in a way that is very similar to Azathioprine. Like Azathioprine it is often described as a "steroid-sparing agent". The benefits of Mycophenolate for patients with MG remain unclear. Two clinical trials have been completed, with Mycophenolate used for 12 weeks in the first trial and nine months in the second. Mycophenolate did not show a beneficial effect in either trial either with respect to improving MG symptoms or with respect to permitting a reduction in the dose of prednisone. Nevertheless, many neurologists believe that Mycophenolate is an excellent option for patients with MG. One additional point worth mentioning is that the available evidence suggests that Mycophenolate, like Azathioprine, may take many months (perhaps even more than a year) to fully take effect. Mycophenolate, therefore, is often use in conjunction with prednisone – with the prednisone dose being gradually tapered (and hopefully discontinued) once the effects of Mycophenolate have become apparent. While taking Mycophenolate, it is important to have regular monitoring for side effects in the form of a blood count and measurement of liver enzymes.
Cyclosporine is another immune suppressive steroid-sparing agent, sometimes used in the treatment of MG. Cyclosporine is taken orally, twice per day. There is some data from clinical trials suggesting the effectiveness of cyclosporine in the treatment of patients with MG, but it tends to be used less frequently now than in the past. The time from initiation of treatment to evidence of benefit (either with respect to symptoms of MG or the ability to reduce the prednisone dose) is unclear, but likely in the order of many months. Potential side effects of cyclosporine include high blood pressure and kidney damage. Those taking cyclosporine should probably have blood levels monitored periodically as well as regular blood work to check kidney function.
Methotrexate is also an immune suppressive agent that has been proposed to have value in the treatment of patients with MG. Methotrexate is taken orally, but unlike other medications for MG, it is necessary to only take the medication once per week. The evidence, however, is uncertain l and there is currently an ongoing clinical trial of methotrexate for patients with MG who require prednisone to control their symptoms. The goals of this trial are to determine whether treatment with methotrexate over a period of 12 months results in improved symptoms of myasthenia and permits reduction in the dose of prednisone. Please contact to learn more about this trial, whether you may be eligible and how to participate.
Plasma exchange, also known as plasmapheresis, is a form of treatment that works by modulating the immune system. Plasma exchange is typically reserved for the treatment of MG exacerbations or crises (i.e. episodes of difficulty breathing or swallowing, or severe limb weakness). Plasma exchange requires intravenous access; while this may be accomplished using a regular IV, it often requires placement of a semi-permanent catheter or port (as is used for administration of chemotherapy). Plasma exchange is typically administered either daily or every other day, for a total of 4-5 exchanges. A major advantage of plasma exchange is that its beneficial effects may be seen quickly – within the time frame of days to weeks. A significant drawback to plasma exchange is that the beneficial effects are also typically short-lived, lasting perhaps for several weeks or at most a few months. Complications related to plasma exchange are largely related to the need for a catheter or port for intravenous access – discomfort, infection and clot formation.
Also known as IVIg or gammaglobulin, intravenous immunoglobulin is another form of immune modulatory therapy. We think about IVIg as being in the same category of treatment as plasma exchange insofar as it also works quickly ‐ within the order of days to weeks – but its benefits are short-lived, lasting only weeks to months. IVIg, as the name implies, is administered via intravenous infusion. A full course of treatment is typically given over 3-5 days with each infusion taking several hours to administer. IVIg, as with plasma exchange, is primarily used to treat MG crises or exacerbations, but occasionally as bridge while waiting for the effects of one of the steroid-sparing agents (e.g. azathioprine, mycophenolate, etc.) to become apparent. The side effects of IVIg mostly result from its effect on increasing the viscosity of blood – kidney failure, heart attack and stroke; fortunately these complications are quite rare and the treatment is usually well tolerated.
Thymectomy is a term used to describe the removal of the thymus gland. The theory behind thymectomy is that the thymus gland is one of the places where the immune system receives its education learning what is "self" and what is "foreign" and how to differentiate between the two (see About MG for more information). In this sense, the thymus gland is like the "school" at which the immune system has been educated. Since the immune system inadequately distinguishes between "foreign" and "self" in MG (i.e. the immune system isnt learning well in school [the thymus gland]), it might be beneficial to remove the thymus gland (i.e. take the immune system students out of the school that's giving them a bad education). This is obviously an overly simplified explanation, but hopefully helps to provide some insight into the rationale for thymectomy in MG. The goal of thymectomy is to limit the need for immune suppressive and immune modulatory therapies (see sections on Prednisone, Azathioprine, Mycophenolate, Cyclosporine). The risks relate to the potential side effects of surgery (e.g. infection), the possibility that the physical stress of the surgery will exacerbate the myasthenia and, depending on the type of thymectomy performed, a surgical scare of some sort.
There are many different techniques that are used to remove the thymus gland, some require extensive surgery and others are more limited. Thymctomy is a form of treatment for MG that has been around for a long time, but remains unproven in any form. In fact, there is sufficient uncertainty about its place in the management of patients with MG that the international community is currently undertaking a randomized controlled trial (the MGTX study).