4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=miast… 1/18

Official reprint from UpToDate www.uptodate.com ©2014 UpToDate

AuthorShawn J Bird, MD

Section EditorsJeremy M Shefner, MD, PhDIra N Targoff, MD

Deputy EditorJohn F Dashe, MD, PhD

Treatment of myasthenia gravis

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Jul 2014. | This topic last updated: Jul 31, 2013.

INTRODUCTION — Myasthenia gravis (MG), once a uniformly disabling and even fatal disorder, can be managedeffectively with current therapeutic strategies. Many patients can even achieve sustained remission. Thetherapeutic approach has certain general principles, but it is highly individualized for each patient. It depends uponthe age of the patient, the severity of the disease, particularly dictated by respiratory or bulbar involvement, and thepace of progression [1­4].

This topic will discuss the general treatment of MG. Detailed reviews of chronic immunomodulating therapies forMG and thymectomy for MG are found separately. Myasthenic crisis and the treatment of ocular MG and MG inpregnancy are also discussed in greater detail separately. (See "Chronic immunomodulating therapies formyasthenia gravis" and "Thymectomy for myasthenia gravis" and "Management of myasthenia gravis inpregnancy" and "Ocular myasthenia gravis" and "Myasthenic crisis".)

OVERVIEW — There are four basic therapies used to treat MG:

Symptomatic treatments (anticholinesterase agents)Chronic immunomodulating treatments (glucocorticoids and other immunosuppressive drugs)Rapid immunomodulating treatments (plasmapheresis and intravenous immune globulin)Surgical treatment (thymectomy)

Symptoms can be treated with acetylcholinesterase inhibitors (also called anticholinesterase medications). Thesemedications are all that is ever needed for some patients. Pyridostigmine bromide (Mestinon) is the maincholinesterase inhibitor currently in use. (See 'Symptomatic treatment' below.)

However, most patients with MG require some form of immunotherapy at some point in their illness, if notindefinitely. Even when immunotherapeutic drugs are used, it is common to continue the use of anticholinesterasemedications in order to reduce the dosage of immunosuppressive drugs and therefore minimize their adverseeffects. Balancing the improvement of MG symptoms with the side effects of the immunotherapeutic agents isalways a challenge for the clinician and patient.

Commonly used immunotherapeutic drugs in MG are prednisone, azathioprine, cyclosporine, and mycophenolatemofetil. In some circumstances, particularly in those with refractory MG, other agents such as rituximab, monthlypulse cyclophosphamide, and tacrolimus may be considered. (See "Chronic immunomodulating therapies formyasthenia gravis".)

Plasmapheresis and intravenous immune globulin (IVIG) are rapid immunotherapies that work quickly but have ashort duration of action. These are usually reserved for certain situations, such as myasthenic crisis, preoperativelybefore thymectomy, as a "bridge" while initiating slower acting immunotherapies, or as an adjuvant to otherimmunotherapeutic medications in patients with refractory MG. (See 'Rapid immunotherapies' below.)

Many experts believe that thymectomy is beneficial in those patients less than age 60 who have generalized MGwithout thymoma, although there are no prospective randomized, blinded, controlled trials [5]. However, it generally

®®

4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=miast… 2/18

takes years for the benefits of thymectomy to accrue. (See "Thymectomy for myasthenia gravis".)

The time of onset of clinical effect of each of these therapies for MG varies considerably (table 1). This plays alarge role, in addition to the pace and severity of the disease, in choosing the appropriate therapy for a givenpatient.

SYMPTOMATIC TREATMENT — The initial therapy for most patients with myasthenia gravis (MG) is an oralanticholinesterase (ie, acetylcholinesterase inhibitor) medication, usually pyridostigmine bromide.Acetylcholinesterase inhibitors retard the degradation of acetylcholine (ACh) that occurs by enzymatic hydrolysis inthe neuromuscular junction [6]. As a result, the effect of ACh is prolonged, leading to a variable improvement instrength.

Acetylcholinesterase inhibitors provide marked improvement in some patients and little or none in others. Often thesymptom improvement may be mixed, with marked improvement in some symptoms but not others (for example,resolution of neck weakness and ptosis with persistence of diplopia). In general, limb and bulbar symptoms(dysphagia, fatigable chewing, and dysarthria) respond better to anticholinesterase drugs than the ocularmanifestations (ptosis and diplopia). Diplopia is particularly resistant to these medications in many patients [7].

Acetylcholinesterase inhibitors are the first line of treatment due to their safety and ease of use. Pyridostigmine(Mestinon) is the usual choice. Neostigmine is available but not commonly used. Acetylcholinesterase inhibitorsprovide only symptomatic therapy and are usually not sufficient in generalized MG. Nonetheless, in some patientsthis is the only therapy ever needed for good control.

Pyridostigmine dosing — Pyridostigmine has a rapid onset of action (15 to 30 minutes) with peak action at abouttwo hours, and its effects last for three to four hours, sometimes longer. Despite its short duration of action, somepatients can use it quite effectively with doses every six hours or three time a day. Others need a dose every threehours to maintain symptomatic benefit.

For adults and older adolescents, a common starting dose is pyridostigmine 30 mg three times a day. Thedose is then titrated by its effect. The maximal dose and frequency is usually 120 mg every four hours whileawake. An occasional patient will need to take a dose every three hours, but never at shorter intervals.Almost all adult patients require a total daily dose of ≤960 mg, divided into four to eight doses.

For children and younger adolescents, the initial dose is 0.5 to 1 mg/kg every four to six hours [8,9], up to atotal daily dose of 7 mg/kg.

Pyridostigmine is available as scored 60 mg tablets and as a liquid formulation. Pyridostigmine is also available inan intravenous preparation and can be given in patients who cannot take oral drugs. This is usually in the setting ofmyasthenic crisis. (See "Myasthenic crisis".)

It should be kept in mind that no fixed pyridostigmine dosing schedule fits all patients. Most adult patients whorespond do so in the range of 60 to 90 mg every four to six hours while awake. Some adults require as much as120 mg every three to four hours while awake. Doses above this are rarely beneficial and are usually limited by thebothersome cholinergic side effects (see 'Side effects' below). When a patient has significant persistent weaknessdespite the use of pyridostigmine in sufficient doses, or the side effects preclude effective dosing, thenimmunotherapy is generally warranted.

The dose regimen used must be thoughtfully individualized to get symptomatic benefits and to limit unnecessarycholinergic side effects. As an example, many patients only have significant symptoms in the evening. An adultpatient might do well with no pyridostigmine until a lunchtime dose of 60 mg followed four hours and eight hourslater by 90 mg. Those who have trouble chewing or mild dysphagia might benefit by taking a dose 30 minutesbefore a meal. There are numerous combinations that work best for an individual patient, based upon the severityof symptoms, the response to pyridostigmine, and toleration of side effects. Medications that alleviate some of thecholinergic side effects of pyridostigmine may also be helpful (see 'Alleviating side effects' below).

4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=miast… 3/18

A long­acting formulation of pyridostigmine (Mestinon TS, 180 mg) is also available. It is used as a bedtime dose inpatients with persistent, severe weakness upon awakening. Most patients, however, do better after a night's sleep,and those with mild weakness upon awakening may do as well by taking a standard pyridostigmine dose at thattime. Long­acting pyridostigmine is not a good choice for daytime use because its variable release and delayedabsorption make it difficult to provide a consistent effect and to regulate the overall pyridostigmine dose.

Side effects — Adverse effects of pyridostigmine are mostly due to the cholinergic properties of the drug.These cholinergic effects can be dose­limiting in many patients. The most bothersome muscarinic side effectsinclude abdominal cramping and diarrhea. Others are increased salivation and bronchial secretions, nausea,sweating, and bradycardia. Nicotinic side effects are also frequent and include fasciculations and muscle cramping.However, these are usually less bothersome than the gastrointestinal effects.

Alleviating side effects — Taking pyridostigmine with food can help to reduce bothersome gastrointestinal sideeffects. Muscarinic side effects can be controlled in many patients with the use of anticholinergic drugs that havelittle or no effect at the nicotinic receptors (ie, do not produce increased weakness). These include the followingagents:

Glycopyrrolate 1 mgPropantheline 15 mgHyoscyamine sulfate 0.125 mg

These anticholinergic drugs can be taken prophylactically three times a day or, alternatively, with eachpyridostigmine dose.

Prominent diarrhea can be reduced by the addition of loperamide (Imodium) or diphenoxylate hydrochloride­atropinesulfate (Lomotil) with or without other anticholinergic drugs.

Cholinergic crisis — A potential major side effect of excessive anticholinesterase medication is weakness, whichcan be difficult to distinguish from worsening MG. This paradoxical weakening with anticholinesterase medicationsis called "cholinergic crisis." However, cholinergic crisis is rarely if ever seen with dose limitation of pyridostigmineto ≤120 mg every three hours, or a total daily dose of ≤960 mg. Cholinergic crisis is so rare that it should not be thepresumed cause of increasing weakness unless the doses taken are known to significantly exceed this range.Otherwise, even in the presence of cholinergic side effects, it should be assumed that the patient's underlying MGis worsening and appropriate treatment should be initiated.

Some have advocated the use of the edrophonium (Tensilon) test to determine if there is too much or too littleanticholinesterase effect in this setting, but this has not proved to be reliable and is not recommended. (See"Diagnosis of myasthenia gravis", section on 'Tensilon test'.)

CHRONIC IMMUNOTHERAPIES — The second therapeutic modality in MG is the administration ofimmunomodulating agents. Glucocorticoids are widely used as well as other agents, most commonly, azathioprine,mycophenolate mofetil, and cyclosporine. The onset of action varies considerably, and this plays a role in thechoice of therapy (table 1).

The administration of moderate or high doses of glucocorticoids leads to remission in about 30 percent of patientsand marked improvement in another 50 percent. The onset of benefit generally begins within two to three weeks.However, a transient deterioration occurs in up to 50 percent of patients with MG when high­dose glucocorticoidsare started, usually occurring 5 to 10 days after the initiation and lasting around five or six days. For this reason,glucocorticoids are most often started in high doses only in hospitalized patients who are receiving concurrentplasmapheresis or intravenous immune globulin (IVIG) for myasthenic crisis. (See "Myasthenic crisis".)

To avoid the transient worsening, an outpatient glucocorticoid dose escalation regimen works quite effectively.

A detailed discussion of glucocorticoids and other immunomodulating agents for MG as well as the data supportingtheir use is found separately. (See "Chronic immunomodulating therapies for myasthenia gravis".)

4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=miast… 4/18

RAPID IMMUNOTHERAPIES — The rapid therapies used in MG are also immunomodulating but are distinctbecause of their quick onset, transient benefit, and their use in select situations. Both plasmapheresis andintravenous immune globulin (IVIG) start to work quickly (over days), but the benefits are only short term (weeks).These therapeutic modalities are used most often in the following situations:

Myasthenic crisis (see "Myasthenic crisis")

Preoperatively before thymectomy or other surgery (see "Thymectomy for myasthenia gravis")

As a "bridge" to slower acting immunotherapies (see 'Bridge therapy' below)

Periodically to maintain remission in patients with MG that is not well controlled despite the use of chronicimmunomodulating drugs

Plasmapheresis — Plasmapheresis (plasma exchange) directly removes acetylcholine receptor (AChR) antibodiesfrom the circulation. Clinical improvement with plasmapheresis roughly correlates with the reduction in antibodylevels, as illustrated by the following reports [10­12].

In five patients with refractory MG (moderate to severe disability despite treatment with thymectomy, high­dose prednisone and cholinesterase inhibitors), plasmapheresis combined with prednisone and azathioprinetherapy produced clinical improvement [10]. Serial determinations of serum AChR antibody titers showed adecline to a mean of 21 percent of the baseline levels concurrently with improved strength. Clinicallyimproved patients maintained lowered AChR titers, whereas clinical relapses were associated with a reboundin AChR titers.

In seven patients with acquired MG who had elevated serum AChR antibody titers there was an inverseassociation between improvement of muscle strength and fall of anti­AChR titers [11]. There was a minimumtime lag of two days for the clinical response to plasmapheresis.

The beneficial clinical effect of plasmapheresis is usually seen within days, but the benefit typically lasts only threeto six weeks. In addition, the AChR antibody levels rebound within weeks if no concurrent immunotherapy (eg,glucocorticoids) is used.

Plasmapheresis is an established treatment for seriously ill patients in the midst of myasthenic crisis. Theevidence supporting its use in this situation is discussed separately. (See "Myasthenic crisis", section on'Plasmapheresis'.)

Plasmapheresis is not a useful long­term treatment, since the need for repeated exchanges often leads to problemswith venous access (see 'Complications' below).

A potential innovation, not widely adapted, is the use of plasmapheresis with an immunosorbent column consistingof staphylococcal protein A [13]. This technique more efficiently removes IgG, the immunoglobulin that includesthose against acetylcholine receptors in MG.

In a further refinement, a Japanese group has designed an acetylcholine receptor antibody­specific immunosorbentcolumn using a peptide isolated from the acetylcholine receptor of Torpedo Californica, called Medisorba MG. Thiscolumn is targeted to remove the blocking acetylcholine receptor antibody [14]. This technique is approved for usein Japan where it has produced clinical improvement in 78 percent of cases [15]. Its potential advantages includeselective removal of anti­AChR antibodies without removing other useful immunoglobulins from the plasma and norequirement for albumin replacement. However, it has limited clinical use and has not yet been shown to besuperior to plasmapheresis with regard to efficacy, cost, and safety.

Course of treatment — A typical course of treatment consists of five exchanges (3 to 5 L of plasma each) over7 to 14 days. The replacement fluid is albumin when used in the treatment of MG. Although done daily in somecircumstances, exchanges done every other day are probably more effective in reducing the antibody levels due to

4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=miast… 5/18

the time it takes for the extravascular immunoglobulin to re­equilibrate after each plasma exchange. (See"Therapeutic plasma exchange: Prescription and technique".)

Complications — Repeated plasmapheresis invariably leads to inadequate peripheral venous access and thenrequires placement of a large bore, double lumen central catheter (subclavian or internal jugular). Significant chroniccatheter complications can result, such as infection and thrombosis. In addition to the catheter complications,plasmapheresis can also produce other adverse effects including bleeding, hypotension, cardiac arrhythmias,muscle cramps, and a toxic reaction to the citrate used in the procedure [16]. (See "Therapeutic plasma exchange:Complications".)

Despite these concerns, plasmapheresis can be used safely for patients with MG. In an analysis of 42 patientswith moderate­to­severe MG who were treated with plasmapheresis in a prospective trial, there were nocomplications in 55 percent and mild­to­moderate complications that did not require stopping treatment in 45percent [17]. The adverse events in this study were mainly citrate reactions and peripheral vascular accessproblems that were easily managed. In most cases, plasmapheresis was performed in the outpatient setting (90percent) using peripheral venous access (83 percent).

Intravenous immune globulin — Intravenous immunoglobulin (IVIG) is pooled immunoglobulin from thousands ofdonors. The mechanism of action for IVIG in MG is uncertain. As with plasmapheresis, the effect of IVIG is seentypically in less than a week, and the benefit can last for three to six weeks. (See "General principles in the use ofimmune globulin", section on 'Mechanisms of action'.)

IVIG is used in the same setting as plasmapheresis to quickly reverse an exacerbation of myasthenia. The limitedevidence supporting its use in this situation is discussed separately. (See "Myasthenic crisis", section on'Intravenous immune globulin'.)

IVIG also offers an alternative to plasmapheresis or multiple immunosuppressive agents in select patients withrefractory MG, as a preoperative treatment before thymectomy [18,19], or as a "bridge" to slower actingimmunotherapies.

As with myasthenic crisis, there are limited data regarding the effectiveness of IVIG for MG without crisis [20,21].

In a double­blind trial, 51 patients with mild to moderate MG and worsening weakness were randomlyassigned to IVIG (2 g/kg given over two days) or placebo (an equivalent volume of dextrose 5 percent inwater) [22]. Exclusion criteria included respiratory distress, vital capacity <1 liter, and severe swallowingdifficulty. Patients treated with IVIG showed a modest but statistically significant improvement comparedwith placebo in the Quantitative Myasthenia Gravis (QMG) Score for disease severity at day 14. Theimprovement persisted but failed to achieve statistical significance at day 28. In subgroup analysis, IVIGtreatment was associated with clinically and statistically significant improvement in patients with moresevere disease at study onset (QMG >10.5), but no improvement was observed in patients with milderdisease (QMG <10.5).

A double­blind randomized trial compared treatment with IVIG versus plasmapheresis for 81 adults with MGand worsening weakness requiring change in therapy [23]. At baseline, 59 percent of patients had milddisease, 40 percent had moderate disease, while only 1 percent had severe disease. Patients who had aflare producing moderate to severe disease (a QMG score >10.5) were treated. At day 14, a similarproportion of patients assigned to IVIG and plasmapheresis had improved (69 versus 65 percent) and theduration of improvement was also similar with longer follow­up.

In earlier observational reports, IVIG was effective in nearly 70 to 75 percent of patients with MG [24,25].

Dose and side effects — The total dose of IVIG is 2 g/kg, usually over two to five days. Spreading the doseover more days is preferable in those who have renal disease, congestive heart failure, or are elderly.

The side effects of IVIG [26,27] are most commonly mild and are related to the infusion rate. These include

4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=miast… 6/18

headache, chills, dizziness, and fluid retention. Other uncommon complications include aseptic meningitis, acuterenal failure, thrombotic events, and anaphylaxis.

The acute nephrotoxicity that occurs in some patients appears to be related to the high sucrose content of somepreparations of IVIG; the risk is increased with underlying renal insufficiency. Anaphylaxis has been associatedwith IgA deficiency; however, it is rarely seen in patients treated for autoimmune neuromuscular diseases [27].Thrombotic events associated with IVIG use include myocardial infarction, stroke, and pulmonary embolism. (See"General principles in the use of immune globulin" and "Immune globulin therapy in primary immunodeficiency".)

THERAPEUTIC APPROACH — The above discussion details the various options in the treatment of the patientwith MG along with certain general principles that can act as a framework for treating patients (see 'Overview'above). However, it should always be kept in mind that the treatment of MG is highly individualized for eachpatient. Treatment choices depend on the age of the patient, the severity of the disease, particularly the presenceof bulbar or respiratory symptoms, and the pace of progression.

In addition, special circumstances can dictate different approaches to treat MG. This section will review theapproach in adults with generalized MG and ocular MG, adults over 60 years of age, and children. The treatment ofMG in pregnancy and approach to severe MG exacerbations including myasthenic crisis is mentioned below but isdiscussed in greater detail separately. (See "Management of myasthenia gravis in pregnancy" and "Myastheniccrisis".)

Generalized myasthenia — The initial step in most adult patients with mild or moderate disease is symptomatictherapy in the form of pyridostigmine bromide (see 'Symptomatic treatment' above). Those with severe disease, orrapidly worsening disease, should be treated much like those in myasthenic crisis (see "Myasthenic crisis") usingrapid therapies (ie, intravenous immunoglobulin or plasmapheresis) followed by longer­acting immunotherapies (see"Chronic immunomodulating therapies for myasthenia gravis") such as glucocorticoids, azathioprine,mycophenolate mofetil, or cyclosporine.

When starting pyridostigmine for an older adolescent or adult, we begin at 30 mg (1/2 tab) with meals three times aday for two to three days to assess the cholinergic side effects (see 'Pyridostigmine dosing' above). For those withexcessive cholinergic side effects we add an agent (eg, glycopyrrolate 1 mg with each pyridostigmine dose) toblock those bothersome symptoms. For those who tolerate the pyridostigmine well, with or without anticholinergics,we increase the dose by 30 mg increments until we get to a good therapeutic effect or are limited by side effects.The maximum dose is usually 120 mg every four hours while awake. An occasional patient may need to take itevery three hours while awake. For those with bothersome symptoms upon awakening in the morning, we use along­acting form of pyridostigmine (Mestinon TS 180 mg) at bedtime.

For children and younger adolescents, the initial dose is 0.5 to 1 mg/kg every four to six hours (see 'Pyridostigminedosing' above). This can be titrated up slowly based on the therapeutic response and side­effects. The maximaldaily dose is 7 mg/kg per 24 hours divided in five to six doses.

For those patients on pyridostigmine alone whose symptoms are under good control or in remission, we simplyfollow their clinical course. Thymectomy should be considered in all adult patients under age 60 as well (see"Thymectomy for myasthenia gravis"). Although there are some patients who do well long­term on pyridostigminealone, most patients with generalized MG ultimately require some form of immunotherapy (see "Chronicimmunomodulating therapies for myasthenia gravis").

Addition of immunomodulating agent — An immunotherapeutic agent is usually required for patients whoremain significantly symptomatic on pyridostigmine, or who become symptomatic again after a temporary responseto pyridostigmine. The choice of agent – most often prednisone, azathioprine, mycophenolate, or cyclosporine –depends on many factors. These include the relative contraindications to glucocorticoids (such as diabetes oradvanced age), liver disease (precluding azathioprine use), renal disease (precludes cyclosporine use), orleukopenia (problematic for both azathioprine and mycophenolate). The desired time for response onset also is afactor (table 1), varying from two to three weeks with prednisone to 6 to 12 months with azathioprine. Cost is

4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=miast… 7/18

another important consideration. (See "Chronic immunomodulating therapies for myasthenia gravis".)

In young adult patients, particularly those of child­bearing potential, we favor the use of glucocorticoids. We oftencan get a good response with high doses initially and then maintain that response after a slow taper down to lowdoses (on the order of 10 mg daily of prednisone). We also use glucocorticoids in older individuals who need arelatively quick response to immunotherapy and then try to add another agent (most often azathioprine ormycophenolate mofetil) to replace the glucocorticoids for the long term.

There are a number of reasonable approaches to starting prednisone, including daily and alternate day dosing.Dosing of glucocorticoids, including dose escalation and tapering, is discussed separately. (See "Chronicimmunomodulating therapies for myasthenia gravis", section on 'Glucocorticoids'.)

For patients who cannot be tapered to low doses without clinical relapse or in those patients where long­termprednisone is not desirable, even at low doses, another immunomodulating agent is substituted.

We add a glucocorticoid­sparing agent, or glucocorticoid replacement, when we are down to the lowest dose ofprednisone that will maintain a reasonable clinical response. Effective glucocorticoid­sparing agents includeazathioprine, mycophenolate mofetil, and cyclosporine. (See "Chronic immunomodulating therapies for myastheniagravis", section on 'Glucocorticoid­sparing agents'.)

After the minimum time to onset of clinical response for the added immunotherapy (eg, often 12 months or more forazathioprine) has passed, we then slowly taper prednisone to as low a dose as can be achieved, preferably none atall. After the glucocorticoids have been tapered, we then try to taper pyridostigmine. Many, but certainly not all,patients can be minimally symptomatic or in remission on one immunotherapy agent alone.

Bridge therapy — For those patients with MG in whom it is especially desirable to avoid glucocorticoids (suchas those with poorly controlled diabetes) or for those who are not successfully weaned to lower doses ofprednisone, we often use monthly courses of IVIG until the more slowly acting immunotherapy takes effect.Monthly plasmapheresis is an alternative to IVIG. However, venous access problems develop with frequent use ofplasmapheresis, making it less practical than IVIG for use as a bridge therapy.

Refractory disease — There is a small cohort of patients with generalized MG who are refractory to, or arelimited by the specific toxicities of, the first­line immunotherapies (eg, azathioprine, mycophenolate, orcyclosporine). Some require unacceptably high doses of glucocorticoids despite concurrent use of these agents. Inthese refractory patients, monthly IVIG or the use of rituximab is often beneficial. (See "Chronic immunomodulatingtherapies for myasthenia gravis", section on 'Rituximab'.)

Need for thymectomy — In parallel with symptomatic treatment and immunotherapeutic agents for MG, weconsider thymectomy because of its potential longer­term benefit. (See "Thymectomy for myasthenia gravis".)

Patients with thymoma clearly need surgical treatment. However, the need for thymectomy is less certain in thosewith nonthymomatous tissue. We advise such patients that the likelihood of medication­free remission is abouttwice as high with thymectomy than without, and that the likelihood of becoming asymptomatic is about one and ahalf times as high with thymectomy [5]. We also emphasize that the benefit of thymectomy is delayed and accruesover several years postoperatively. (See "Thymectomy for myasthenia gravis", section on 'Efficacy'.)

We advocate thymectomy as soon as the patient's degree of weakness is sufficiently controlled to permit surgery,if the patient is amenable to that surgery. We also prefer to have patients on relatively low doses of glucocorticoids,if possible, to avoid postoperative problems with wound healing.

For patients with preoperative bulbar or respiratory symptoms, we try to defer surgery until they are reasonably wellcontrolled. We administer IVIG or perform a series of plasma exchanges one or two weeks before surgery, if theserespiratory or bulbar symptoms persist. The exact timing of surgery and what techniques are appropriate are issuesnot settled.

Ocular myasthenia — The elements of treatment for ocular myasthenia gravis (OMG) are the same as with

4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=miast… 8/18

generalized MG. However, differences in the symptomatology, disability, and prognosis lead to some differences inthe treatment approach for these patients. This is discussed in more detail separately. (See "Ocular myastheniagravis", section on 'Treatment'.)

Age 60 and over — We do not routinely suggest thymectomy in patients over 60 years of age, unless a thymomais present. (See "Thymectomy for myasthenia gravis", section on 'Patient age and severity of disease' and "Clinicalpresentation and management of thymoma and thymic carcinoma".)

Although there are no firm data to support a strict age limit for this surgical therapy, many feel that thymectomy isless likely to be beneficial in this age group due to the high incidence of thymic involution and an increasedoperative risk due to comorbidities. We use age 60 as a rough rule of thumb, but this is moderated by the patient'soverall health, functional age, and the patient's wishes after reviewing the issues with him or her. Despite thereluctance at many centers to perform this surgery on older patients with MG, there is some evidence that patientsover age 60 may benefit from the procedure [28].

Other than a tendency to use glucocorticoids more sparingly in this group, the use of pyridostigmine, azathioprine,and mycophenolate mofetil does not differ from that detailed above. Due to the potential renal side effects, we donot commonly use cyclosporine in these patients. There are few studies that look at the treatments in thisparticular age group. However, the usefulness of immunotherapy is supported by a study of outcome at one year orlonger in 149 patients with disease onset after age 60 who were treated with azathioprine with or without prednisone[29]. Better outcomes and fewer side effects were observed when prednisone was avoided or was combined withazathioprine.

Children — As with adults, the treatment of children with MG should be individualized based on the severity andpace of the disease [8,9,30]. Pyridostigmine is the first line of therapy (see 'Pyridostigmine dosing' above). Ifanticholinesterase medications are not sufficient, plasmapheresis or intravenous immune globulin may be used, butthe benefits are transient.

Glucocorticoids are generally limited to severe disease that is unresponsive to these interventions. Glucocorticoidsretard bone growth, increase the risk of adult osteoporosis, and are especially problematic for chronic use inchildren. Azathioprine, mycophenolate mofetil, and cyclosporine have been used successfully in juvenile MG[9,30], but concerns about serious adverse effects, including impaired fertility and the late development ofmalignancy, are of even greater concern than in adults.

As a long­term treatment for MG, thymectomy has been performed successfully and with low morbidity in children[31]. Thymectomy is a widely accepted option for peripubertal and postpubertal children with generalized MG whohave positive acetylcholine receptor antibodies or who are seronegative [8,9,30­32]. The rates of improvement andremission seen in uncontrolled series appear to be similar to that reported in adults after thymectomy [31].Thorascopic thymectomy, potentially a more acceptable treatment in this age group, has been used successfully ina small case series [33]. The likelihood of improvement or remission after a single procedure (thymectomy)compared with long­term immunotherapy makes this option a reasonable consideration in all children who havemore than mild disease. No significant deleterious consequences of removing the thymus in childhood have beenreported [30].

Similar to adults with MuSK antibody­positive MG (see "Thymectomy for myasthenia gravis", section on 'MuSKantibody­positive myasthenia'), children with MuSK­positive MG have not been shown to benefit from thymectomy.Therefore, thymectomy is not recommended for this group. The role of thymectomy in prepubertal children remainscontroversial. This group has a higher incidence of spontaneous remission and is also more likely to beseronegative, making confirmation of the diagnosis more difficult [8,30].

The clinical outcome in childhood MG varies with age of onset, race, and sex [34]. White children with prepubertalonset have the best prognosis. The spontaneous remission rate is 44 percent in these children, and they respondwell to early thymectomy.

Pregnancy and the neonate — Pregnancy has a variable effect on the course of MG. It does not worsen the long­

4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=miast… 9/18

term outcome, but the MG may worsen during the course of pregnancy. The first trimester and the monthpostpartum are the periods of highest risk of exacerbation.

The management of myasthenia in pregnancy is discussed separately. (See "Management of myasthenia gravis inpregnancy".)

Transient neonatal MG develops in 10 to 20 percent of infants born to myasthenic mothers due to transplacentalpassage of antiacetylcholine receptor antibodies. Neonatal myasthenia is discussed separately. (See"Neuromuscular junction disorders in newborns and infants".)

Myasthenic crisis — Myasthenic crisis is a life­threatening condition, and it is characterized by neuromuscularrespiratory failure. Severe bulbar weakness that produces dysphagia and aspiration often complicates therespiratory failure. Patients in myasthenic crisis typically experience increasing generalized weakness as awarning, although occasionally a patient will present with respiratory insufficiency out of proportion to their limb orbulbar weakness.

The evaluation and treatment of myasthenic crisis is discussed separately. (See "Myasthenic crisis".)

Drugs that may exacerbate myasthenia — Some medications may cause a significant increase in weakness inpatients with MG (table 2). These include aminoglycoside antibiotics, beta blockers, procainamide, quinidine,quinine, and phenytoin [35]. A number of other drugs may unmask or exacerbate MG, particularly theneuromuscular blocking agents used during anesthesia, which can lead to prolonged postoperative weakness andventilator dependence.

In a literature review of drug­induced myasthenia, the drugs that were most likely to have a negative impact on MGwere those used in the treatment of the disease, including [36]:

High­dose prednisoneOveruse of anticholinesterase drugsAnesthesia and neuromuscular blockers for thymectomy

Aminoglycoside­related postoperative respiratory depression caused the greatest frequency of drug­inducedneuromuscular blockade.

Penicillamine, used in other autoimmune diseases, induces an autoimmune myasthenic syndrome in approximately1 percent of cases. It simulates primary MG in that it can induce ocular or generalized weakness with theproduction of acetylcholine receptor antibodies [37,38]. The myasthenic symptoms eventually resolve after thepenicillamine is discontinued. (See "Differential diagnosis of myasthenia gravis", section on 'Penicillamine­inducedmyasthenia'.)

The following drugs warrant special concern in patients with MG (table 2):

Aminoglycosides should be avoided and only used if absolutely necessary with close monitoring.

Telithromycin has been associated with exacerbations or unmasking of MG in several case reports, oftenwithin two hours of the first dose [39,40]. A black box warning has been added to the drug label stating thattelithromycin should not be used in patients with MG. (See "Azithromycin, clarithromycin, and telithromycin",section on 'Warnings about telithromycin'.)

Neuromuscular blocking agents may be necessary for anesthesia or intubation, but their use delaysemergence from anesthesia, recovery of muscle strength, and weaning from mechanical ventilation [41].These drugs should be judiciously titrated if used.

Lidocaine and procaine may cause worsening if injected intravenously.

Magnesium sulfate is relatively contraindicated because magnesium has a significant inhibitory effect onacetylcholine release.

4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=mias… 10/18

Penicillamine and interferon­alpha should be avoided in patients with MG because they can induce MG.

Fluoroquinolone antibiotics should be used with caution.

All beta blockers should be used with caution.

All glucocorticoids at high doses may cause exacerbation of MG symptoms during early stages oftreatment.

Among anticonvulsants, phenytoin and gabapentin have been rarely reported to exacerbate MG, but thesedrugs may be used if needed. Experimental evidence suggests that ethosuximide and carbamazepine maycause increased weakness, but there are no clinical reports.

Central nervous system depressants, opioids, and muscle relaxants may increase MG symptoms whenthese agents are used concurrently or given in high doses.

Statin treatment may be associated with MG, as suggested by a few case reports and case series [42­46]that describe a total of 12 patients with new or worsening MG in the context of extensive use of these drugs.Exacerbation of pre­existing MG within a few months of starting statin therapy was reported in eight patients[44­46], including six from a single­center retrospective study of 170 patients with MG who were surveyedabout statin treatment [46]. Symptoms of de novo MG developed within weeks of starting statins in fourpatients [44,45]. Unmasking of subclinical MG due to statin­related myotoxicity appeared to be the mostlikely explanation for some of new cases, and the coincidental occurrence of autoimmune MG with statintherapy was also a consideration.

A good rule­of­thumb in generalized MG is to assume that any medication may exacerbate MG and to watch forworsening following the introduction of a new medication. Whether the association with clinical worsening of MG iscoincidental or casually related may require withdrawal from the medication and a rechallenge.

Immunizations — Patients with generalized MG who develop respiratory infections are at increased risk ofmyasthenic exacerbations and respiratory compromise [47]. This increased risk may be shared by patients withocular MG of more recent onset (less than three years), because they are still at risk of progressing to generalizeddisease. In contrast, patients with stable ocular MG of three or more years duration are much less likely to developgeneralized disease and therefore are not considered to be at increased risk of myasthenic exacerbations orrespiratory compromise.

Current guidelines recommend annual seasonal influenza vaccination for all individuals receivingimmunosuppressive therapy, and for those with neurologic conditions, including neuromuscular disorders such asgeneralized MG, or ocular MG within three years of onset, that can potentially compromise the handling ofrespiratory secretions. (See "Seasonal influenza vaccination in adults" and "Seasonal influenza in children:Prevention with vaccines", section on 'Indications'.)

A population­based study suggests that the inactivated (intramuscular) influenza vaccine is safe in adults with MG[48]. Furthermore, inactivated vaccines (eg, pneumococcal and intramuscular influenza vaccines) generally areconsidered safe in adults or children with immunocompromising conditions, while live vaccines generally areavoided. Thus, patients being treated with immunotherapy for MG should not receive the live­attenuated(intranasal) influenza vaccine.

The pneumococcal vaccine is recommended for all individuals with chronic pulmonary conditions and for thosereceiving immunosuppressive therapy. While MG does not usually result in chronic pulmonary disease, we suggestpneumococcal vaccination for all individuals with generalized MG, and for those with ocular MG who are withinthree years of onset, because of the risk that infection may trigger an MG exacerbation or crisis. (See"Pneumococcal vaccination in adults" and "Pneumococcal (Streptococcus pneumoniae) conjugate vaccines inchildren".)

4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=mias… 11/18

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and“Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5 to 6 gradereading level, and they answer the four or five key questions a patient might have about a given condition. Thesearticles are best for patients who want a general overview and who prefer short, easy­to­read materials. Beyond theBasics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the10 to 12 grade reading level and are best for patients who want in­depth information and are comfortable withsome medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e­mail thesetopics to your patients. (You can also locate patient education articles on a variety of subjects by searching on“patient info” and the keyword(s) of interest.)

Basics topic (see "Patient information: Myasthenia gravis (The Basics)")

SUMMARY AND RECOMMENDATIONS

The four basic therapies for MG include symptomatic treatments (anticholinesterase agents), chronicimmunotherapies (glucocorticoids and other immunosuppressive drugs), rapid immunotherapies (plasmaexchange and intravenous immune globulin [IVIG]), and thymectomy. The time of onset of clinical effect ofeach of these therapies for MG varies considerably (table 1). (See 'Overview' above.)

We recommend treatment with acetylcholinesterase inhibitors as the first line of treatment for symptomaticMG (Grade 1B). Pyridostigmine is the most widely used choice. For adults and older adolescents, a typicalstarting dose is 30 mg three times a day. For children and younger adolescents, the initial dose is 0.5 to 1mg/kg every four to six hours. The dose of pyridostigmine is then titrated by its effect. (See 'Symptomatictreatment' above.)

Most patients with MG will need some form of immunotherapy in addition to pyridostigmine. We recommendadding immunotherapy for patients who remain significantly symptomatic on pyridostigmine, or who becomesymptomatic after a temporary response to pyridostigmine (Grade 1B). Glucocorticoids, azathioprine,mycophenolate mofetil, and cyclosporine are the most widely used (see 'Chronic immunotherapies' above).This approach is discussed in greater detail separately. (See "Chronic immunomodulating therapies formyasthenia gravis".)

Plasmapheresis (with plasma exchange) and IVIG work quickly but have a short duration of action. Inaddition to treatment of myasthenic crisis, these rapid therapies are useful in presurgical treatment ofmoderate to severe MG. They are also used as a "bridge" when initiating slower acting immunotherapies,and as periodic adjuvants to other immunotherapeutic medications in refractory MG. (See 'Rapidimmunotherapies' above.)

We suggest thymectomy for patients without thymoma below age 60 years who have generalized MG andeither have AChR antibodies, or have no detectable AChR or MuSK antibodies (ie, seronegative MG) (Grade2C). We suggest not performing thymectomy in patients with MuSK antibody­associated MG withoutthymoma (Grade 2C). (See 'Generalized myasthenia' above and 'Age 60 and over' above and "Thymectomyfor myasthenia gravis".)

Attempted surgical excision is the treatment of choice for nonmetastatic thymoma and thymic carcinoma.(See "Clinical presentation and management of thymoma and thymic carcinoma", section on 'Management'.)

A number of drugs can unmask or exacerbate MG (table 2). Avoidance of aminoglycoside antibiotics,magnesium sulfate, penicillamine, and interferon­alpha in patients with MG is prudent. Likewise, betablockers, procainamide, quinidine, and quinine should be avoided when possible. Cautious use of drugslisted in the table (table 2), particularly the neuromuscular blocking agents, is advised whenever there is a

th th

th th

4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=mias… 12/18

clear requirement for any of these agents. (See 'Drugs that may exacerbate myasthenia' above.)

The treatment of MG is highly individualized and depends upon the age of the patient, the severity of thedisease, and the pace of progression. Treatment options and suggestions for generalized MG, ocular MG,patients over 60, and children are discussed in detail above. (See 'Generalized myasthenia' above and'Ocular myasthenia' above and 'Age 60 and over' above and 'Children' above.)

For all individuals with generalized MG, and those with ocular MG who are within three years of onset, wesuggest pneumococcal vaccination and annual intramuscular (inactivated) seasonal influenza vaccination(Grade 2C). Patients being treated with immunotherapy for MG should not receive the live­attenuated(intranasal) influenza vaccine. (See 'Immunizations' above.)

The management of MG in pregnancy is discussed separately. (See "Management of myasthenia gravis inpregnancy".)

The management of rapidly worsening MG and myasthenic crisis is discussed separately. (See "Myastheniccrisis".)

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

1. Skeie GO, Apostolski S, Evoli A, et al. Guidelines for treatment of autoimmune neuromuscular transmissiondisorders. Eur J Neurol 2010; 17:893.

2. Farrugia ME, Vincent A. Autoimmune mediated neuromuscular junction defects. Curr Opin Neurol 2010;23:489.

3. Richman DP, Agius MA. Treatment of autoimmune myasthenia gravis. Neurology 2003; 61:1652.4. Keesey JC. Clinical evaluation and management of myasthenia gravis. Muscle Nerve 2004; 29:484.5. Gronseth GS, Barohn RJ. Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence­

based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.Neurology 2000; 55:7.

6. Punga AR, Stålberg E. Acetylcholinesterase inhibitors in MG: to be or not to be? Muscle Nerve 2009; 39:724.7. Liu GT, Volpe NJ, Galetta SL. Eyelid and facial nerve disorders. In: Neuro­Ophthalmology, Liu GT, Volpe NJ,

Galetta SL. (Eds), WB Saunders, Philadelphia 2001. p.496.8. Ionita CM, Acsadi G. Management of juvenile myasthenia gravis. Pediatr Neurol 2013; 48:95.9. Chiang LM, Darras BT, Kang PB. Juvenile myasthenia gravis. Muscle Nerve 2009; 39:423.10. Dau PC, Lindstrom JM, Cassel CK, et al. Plasmapheresis and immunosuppressive drug therapy in

myasthenia gravis. N Engl J Med 1977; 297:1134.11. Newsom­Davis J, Pinching AJ, Vincent A, Wilson SG. Function of circulating antibody to acetylcholine

receptor in myasthenia gravis: investigation by plasma exchange. Neurology 1978; 28:266.12. Gajdos P, Chevret S, Toyka K. Plasma exchange for myasthenia gravis. Cochrane Database Syst Rev 2002;

:CD002275.13. Benny WB, Sutton DM, Oger J, et al. Clinical evaluation of a staphylococcal protein A immunoadsorption

system in the treatment of myasthenia gravis patients. Transfusion 1999; 39:682.14. Miyahara T, Oka K, Nakaji S. Specific immunoadsorbent for myasthenia gravis treatment: development of

synthetic peptide designed to remove antiacetylcholine receptor antibody. Ther Apher 1998; 2:246.15. Nakaji S, Hayashi N. Adsorption column for myasthenia gravis treatment: Medisorba MG­50. Ther Apher Dial

2003; 7:78.16. Rodnitzky RL, Goeken JA. Complications of plasma exchange in neurological patients. Arch Neurol 1982;

39:350.17. Ebadi H, Barth D, Bril V. Safety of plasma exchange therapy in patients with myasthenia gravis. Muscle

4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=mias… 13/18

Nerve 2013; 47:510.18. Pérez Nellar J, Domínguez AM, Llorens­Figueroa JA, et al. [A comparative study of intravenous

immunoglobulin and plasmapheresis preoperatively in myasthenia]. Rev Neurol 2001; 33:413.19. Illa I. IVIg in myasthenia gravis, Lambert Eaton myasthenic syndrome and inflammatory myopathies: current

status. J Neurol 2005; 252 Suppl 1:I14.20. Gajdos P, Chevret S, Toyka KV. Intravenous immunoglobulin for myasthenia gravis. Cochrane Database

Syst Rev 2012; 12:CD002277.21. Patwa HS, Chaudhry V, Katzberg H, et al. Evidence­based guideline: intravenous immunoglobulin in the

treatment of neuromuscular disorders: report of the Therapeutics and Technology Assessment Subcommitteeof the American Academy of Neurology. Neurology 2012; 78:1009.

22. Zinman L, Ng E, Bril V. IV immunoglobulin in patients with myasthenia gravis: a randomized controlled trial.Neurology 2007; 68:837.

23. Barth D, Nabavi Nouri M, Ng E, et al. Comparison of IVIg and PLEX in patients with myasthenia gravis.Neurology 2011; 76:2017.

24. Arsura E. Experience with intravenous immunoglobulin in myasthenia gravis. Clin Immunol Immunopathol1989; 53:S170.

25. Cosi V, Lombardi M, Piccolo G, Erbetta A. Treatment of myasthenia gravis with high­dose intravenousimmunoglobulin. Acta Neurol Scand 1991; 84:81.

26. Dalakas MC. Intravenous immunoglobulin in the treatment of autoimmune neuromuscular diseases: presentstatus and practical therapeutic guidelines. Muscle Nerve 1999; 22:1479.

27. Dalakas MC. The use of intravenous immunoglobulin in the treatment of autoimmune neuromusculardiseases: evidence­based indications and safety profile. Pharmacol Ther 2004; 102:177.

28. Tsuchida M, Yamato Y, Souma T, et al. Efficacy and safety of extended thymectomy for elderly patientswith myasthenia gravis. Ann Thorac Surg 1999; 67:1563.

29. Evoli A, Batocchi AP, Minisci C, et al. Clinical characteristics and prognosis of myasthenia gravis in olderpeople. J Am Geriatr Soc 2000; 48:1442.

30. Andrews PI. Autoimmune myasthenia gravis in childhood. Semin Neurol 2004; 24:101.31. Tracy MM, McRae W, Millichap JG. Graded response to thymectomy in children with myasthenia gravis. J

Child Neurol 2009; 24:454.32. Evoli A. Acquired myasthenia gravis in childhood. Curr Opin Neurol 2010; 23:536.33. Kolski H, Vajsar J, Kim PC. Thoracoscopic thymectomy in juvenile myasthenia gravis. J Pediatr Surg 2000;

35:768.34. Andrews PI, Massey JM, Howard JF Jr, Sanders DB. Race, sex, and puberty influence onset, severity, and

outcome in juvenile myasthenia gravis. Neurology 1994; 44:1208.35. Wittbrodt ET. Drugs and myasthenia gravis. An update. Arch Intern Med 1997; 157:399.36. Barrons RW. Drug­induced neuromuscular blockade and myasthenia gravis. Pharmacotherapy 1997; 17:1220.37. Russell AS, Lindstrom JM. Penicillamine­induced myasthenia gravis associated with antibodies to

acetylcholine receptor. Neurology 1978; 28:847.38. Kuncl RW, Pestronk A, Drachman DB, Rechthand E. The pathophysiology of penicillamine­induced

myasthenia gravis. Ann Neurol 1986; 20:740.39. Nieman RB, Sharma K, Edelberg H, Caffe SE. Telithromycin and myasthenia gravis. Clin Infect Dis 2003;

37:1579.40. Perrot X, Bernard N, Vial C, et al. Myasthenia gravis exacerbation or unmasking associated with

telithromycin treatment. Neurology 2006; 67:2256.41. Dillon FX. Anesthesia issues in the perioperative management of myasthenia gravis. Semin Neurol 2004;

24:83.42. Parmar B, Francis PJ, Ragge NK. Statins, fibrates, and ocular myasthenia. Lancet 2002; 360:717.43. Engel WK. Reversible ocular myasthenia gravis or mitochondrial myopathy from statins? Lancet 2003;

361:85.44. Cartwright MS, Jeffery DR, Nuss GR, Donofrio PD. Statin­associated exacerbation of myasthenia gravis.

4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=mias… 14/18

Neurology 2004; 63:2188.45. Purvin V, Kawasaki A, Smith KH, Kesler A. Statin­associated myasthenia gravis: report of 4 cases and

review of the literature. Medicine (Baltimore) 2006; 85:82.46. Oh SJ, Dhall R, Young A, et al. Statins may aggravate myasthenia gravis. Muscle Nerve 2008; 38:1101.47. Thomas CE, Mayer SA, Gungor Y, et al. Myasthenic crisis: clinical features, mortality, complications, and

risk factors for prolonged intubation. Neurology 1997; 48:1253.48. Zinman L, Thoma J, Kwong JC, et al. Safety of influenza vaccination in patients with myasthenia gravis: a

population­based study. Muscle Nerve 2009; 40:947.

Topic 5157 Version 11.0

4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=mias… 15/18

GRAPHICS

Commonly used therapies for myasthenia gravis

Time to onset of

effect*Time to maximal

effect*

Symptomatic therapy

Pyridostigmine 10 to 15 minutes 2 hours

Chronic immunotherapies

Prednisone 2 to 3 weeks 5 to 6 months

Azathioprine ~12 months 1 to 2 years

Mycophenolate mofetil 6 to 12 months 1 to 2 years

Cyclosporine and tacrolimus ~6 months ~12 months

Rapid immunotherapies

Plasmapheresis 1 to 7 days 1 to 3 weeks

Intravenous immuneglobulin

1 to 2 weeks 1 to 3 weeks

Surgery

Thymectomy 1 to 10 years 1 to 10 years

* Estimated times are rough guidelines based upon clinical experience in myasthenia gravis.

Graphic 70721 Version 4.0

4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=mias… 16/18

Drugs that may unmask or exacerbate myasthenia gravis*

Anesthetic agents

Chloroprocaine

Diazepam

Ether

Halothane

Ketamine

Lidocaine

Neuromuscular blocking agents

Propanidid

Procaine

Antibiotics

Aminoglycosides

Amikacin

Gentamicin

Kanamycin

Neomycin

Netilmicin

Paromomycin

Spectinomycin

Streptomycin

Tobramycin

Fluoroquinolones

Ciprofloxacin

Gemifloxacin

Levofloxacin

Moxifloxacin

Norfloxacin

Ofloxacin

Others

Ampicillin

Azithromycin

Clarithromycin

Clindamycin

Colistin

Erythromycin

Lincomycin

Antirheumatic drugs

Chloroquine

Penicillamine

Cardiovascular drugs

Beta blockers

Bretylium

Procainamide

Propafenone

Quinidine

Verapamil and calcium channel blockers

Glucocorticoids

Corticotropin

Methylprednisolone

Prednisone

Neuromuscular blockers andmuscle relaxants

Botulinum toxin

Magnesium sulfate and magnesium salts

Methocarbamol

Ophthalmologic drugs

Betaxolol

Echothiophate

Timolol

Tropicamide

Proparacaine

Other drugs

Anticholinergics

Carnitine

Cholinesterase inhibitors

Deferoxamine

Diuretics

Emetine (Ipecac syrup)

Interferon alpha

4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=mias… 17/18

Quinine

Telithromycin

Tetracyclines

Anticonvulsants

Gabapentin

Phenytoin

Trimethadione

Antipsychotics

Chlorpromazine

Lithium

Phenothiazines

Iodinated contrast agents

Narcotics

Oral contraceptives

Oxytocin

Ritonavir and antiretroviral proteaseinhibitors

Statins

Thyroxine

* Drugs listed here should be used with caution in patients with myasthenia gravis. Aminoglycosidesshould be used only if absolutely necessary with close monitoring. Please refer to the text for furtherinformation.

Graphic 62302 Version 6.0

4/8/2014 Treatment of myasthenia gravis

http://www.uptodate.com/contents/treatment-of-myasthenia-gravis?topicKey=NEURO%2F5157&elapsedTimeMs=0&source=search_result&searchTerm=mias… 18/18

Disclosures: Shawn J Bird, MD Nothing to disclose. Jeremy M Shefner, MD, PhD Nothing to disclose. Ira N Targoff, MDConsultant/Advisory Boards: Oklahoma Medical Research Foundation Clinical Immunology Laboratory (myositis antibody testing). John FDashe, MD, PhD Employee of UpToDate, Inc.Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through amulti­level review process, and through requirements for references to be provided to support the content. Appropriately referencedcontent is required of all authors and must conform to UpToDate standards of evidence.Conflict of interest policy

Disclosures