Diagnosis of myasthenia gravis

INTRODUCTION — Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by fluctuating motor weakness involving ocular, bulbar, limb, and/or respiratory muscles. The weakness is due to an antibody-mediated, immunologic attack directed at proteins in the postsynaptic membrane of the neuromuscular junction (acetylcholine receptors or receptor-associated proteins). MG is the most common disorder of neuromuscular transmission.

The diagnosis of MG will be reviewed here. Other aspects of this disorder are discussed separately.

●(See "Pathogenesis of myasthenia gravis".)

●(See "Clinical manifestations of myasthenia gravis".)

●(See "Differential diagnosis of myasthenia gravis".)

●(See "Overview of the treatment of myasthenia gravis".)

●(See "Chronic immunotherapy for myasthenia gravis".)

The evaluation and diagnosis of rare myasthenic syndromes that occur in infants are discussed elsewhere. (See "Neuromuscular junction disorders in newborns and infants", section on 'Neonatal myasthenia gravis' and "Neuromuscular junction disorders in newborns and infants", section on 'Congenital myasthenic syndromes'.)

CLINICAL TESTING — MG should be suspected in patients with fatigable muscle weakness, including those with isolated ptosis and/or diplopia. The weakness from MG is due to autoimmune-mediated impairment at the neuromuscular junction. However, motor weakness may also be due to neurologic dysfunction at multiple other sites, including the brain, brainstem, spinal cord, peripheral nerves, and muscle. Specific examination techniques may be used to help localize motor weakness to the neuromuscular junction. These tests may be useful to help select patients for diagnostic testing, such as those with symptoms that are mild or do not fluctuate. However, they have a low specificity for MG and are therefore not confirmatory tests.

Ice pack test — The ice pack test can be used as part of the neurologic examination for patients with ptosis. The test is based on the physiologic principle that neuromuscular transmission improves at lower muscle temperatures. In patients with MG, ptosis can be overcome temporarily by direct cooling of the eyelid muscles.

To perform the ice pack test, the baseline severity of ptosis is assessed. An ice-filled bag (or surgical glove) is placed on the closed lid for two minutes. The ice is then removed and the extent of ptosis is immediately reassessed. Improvement in ptosis is a positive test result. The sensitivity appears to be approximately 80 percent in those with prominent ptosis due to MG [1-3]. The predictive value of the test has not been established.

It is generally not helpful for those with other ocular symptoms, such as extraocular muscle weakness.

Pharmacologic testing — Administration of a pharmacologic agent to potentiate signal transmission of acetylcholine may be used to help localize symptoms to the neuromuscular junction for conditions like MG characterized by impaired acetylcholine transmission.

●Edrophonium test (historical) – The edrophonium ("Tensilon") test is described here for historical reasons but has fallen out of use due to suboptimal sensitivity and specificity as well as associated adverse risks. The drug is no longer available in the United States and many other countries as of 2018 [4].

Edrophonium chloride is an acetylcholinesterase inhibitor with rapid onset (30 to 45 seconds) and short duration of action (5 to 10 minutes). This agent prolongs the presence of acetylcholine in the neuromuscular junction and results in an immediate increase in muscle strength in many of the affected muscles.

The edrophonium test, if available, is used for patients with obvious ptosis or ophthalmoparesis, in whom improvement after infusion of the drug can be easily observed [5]. Edrophonium is given intravenously in 2 mg incremental doses, typically up to a total dose of 10 mg. Clear improvement of ptosis or ophthalmoparesis indicates a positive result. The sensitivity of the edrophonium test is in the range of 80 to 90 percent but may produce false-negative or false-positive results [1,5,6]. Some patients with clearly established MG may have equivocal or no response to the edrophonium. For others, it can be difficult to quantify improvement due to edrophonium, independent of volition in other muscle groups. Some patients may show improved muscle strength at lower doses but a paradoxical response of greater weakness at higher doses of edrophonium [5]. On the other hand, a positive test is not specific for MG, as it can also occur in other conditions, such as motor neuron disease, brainstem tumors, and compressive cranial neuropathies, each of which can present in a similar fashion [5].

The injection of edrophonium is associated with adverse risks due to the potentiated muscarinic effects of acetylcholine. Patients frequently develop increased salivation and mild gastrointestinal cramping. More seriously, symptomatic bradycardia or bronchospasm can also occur.

●Failure of neuromuscular blockade reversal – Medications to reverse the effect of neuromuscular blockade anesthetic agents are often administered at the end of an interventional or surgical procedure to hasten neuromuscular recovery and facilitate extubation. Neuromuscular weakness may be suspected in patients who do not improve as expected with neuromuscular blockade reversal following general anesthesia. Neuromuscular respiratory failure may be the initial manifestation of MG. (See "Myasthenic crisis", section on 'Clinical presentation' and "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Reversal of neuromuscular block'.)

SEROLOGIC DIAGNOSIS — For most patients with clinical features of MG, the diagnosis may be confirmed by the presence of autoantibodies against the acetylcholine receptor (AChR) or against other muscle receptor-associated proteins (eg, muscle-specific tyrosine kinase [MuSK] or low-density lipoprotein receptor-related protein 4 [LRP4]) (algorithm 1). (See "Clinical manifestations of myasthenia gravis".)

An approximate distribution of diagnostic, commercially available autoantibody results for patients with generalized MG is [7-9]:

●AChR antibodies – 85 percent

●MuSK antibodies – 8 percent

●LRP4 antibodies – 1 percent

●Seronegative – 6 percent

For symptomatic patients who do not have autoantibodies (seronegative), electrodiagnostic testing that shows evidence of impaired signal transmission at the neuromuscular junction is used to confirm the diagnosis of MG. (See 'Electrodiagnostic confirmation for seronegative and atypical presentations' below.)

Acetylcholine receptor antibodies — An immunologic assay to detect the presence of circulating AChR antibodies should be the initial laboratory test performed to confirm the diagnosis of MG. AChR antibodies are found in up to 90 percent of patients with generalized MG (table 1) [7].

Laboratory testing for other autoantibodies is performed to identify MG when AChR antibody testing is nondiagnostic. (See 'Second-line antibody testing' below.)

●Subtypes – There are three AChR antibody assays: binding, blocking, and modulating. Most authors use the term AChR antibody as synonymous with the binding antibodies, and these are what are referred to in most studies that report the diagnostic sensitivity of these tests in MG.

●Testing – Binding antibodies are tested most frequently because this assay is the most sensitive [10-12]. The likelihood of a positive result varies by the severity of symptoms. One study found positive binding antibodies in 93 percent of patients with moderate to severe generalized MG, 88 percent for those with mild generalized MG, and 71 percent for patients with ocular MG [13]. Overall, binding antibodies may be found in approximately 80 to 90 percent of those with generalized disease and in 40 to 70 percent of those with ocular MG [6,7,13,14]. By contrast, blocking and modulating AChR antibodies are present in approximately half of patients with generalized disease [15].

False-positive binding antibodies in low titers have been reported in patients with Lambert-Eaton myasthenic syndrome (5 percent), motor neuron disease (3 to 5 percent), and polymyositis (<1 percent) [12,13,16]. They are also rarely seen in some disorders that are not usually confused with MG: primary biliary cholangitis, systemic lupus erythematosus (SLE), hypothyroidism, thymoma without MG, and in first-degree relatives of patients with MG [17-19].

Blocking and/or modulating antibody testing may be added if available to increase diagnostic specificity for patients with mild or atypical symptoms who are suspected to have false-positive low-titer AChR binding antibody results. However, the overall utility of adding blocking and/or modulating antibodies to binding antibody testing is modest. Assays for modulating AChR antibodies may increase the sensitivity by <5 percent when added to the binding studies [7]. However, false-positive modulating antibodies are common [18,19]. Blocking antibodies are found in fewer than one percent of patients with MG who do not also have positive binding antibodies. In a retrospective single-center study of patients with positive AChR antibodies on neuro-autoimmune antibody panel testing, those with MG had higher mean AChR binding titers (8 nmol/L versus 0.4 nmol/L) and higher rates of positive modulating antibody (89 versus 24 percent) than those with other conditions [19].

●Significance of titers – High AChR antibody titers are more specific for the diagnosis of MG than low titers [19]. However, titers correlate poorly with disease severity between patients. A low-titer or even antibody-negative patient may have much more severe clinical disease than a patient with high titers. In addition, it is not helpful to follow the AChR antibody levels as a marker for improvement in patients being treated for MG. Treatment response in MG is discussed separately. (See "Overview of the treatment of myasthenia gravis", section on 'Treatment goals and response assessment'.)

Serologic testing for AChR antibodies should be performed prior to initiating immune-modulating therapy for MG, as such therapy can sometimes lead to apparent seronegativity [7]. In one cohort of 143 seropositive patients, 9 percent became seronegative after treatment when retested in clinical remission. In addition, repeat serologic testing 6 to 12 months after initial testing has been reported to detect positive seroconversion in approximately 15 percent of patients with MG who were initially seronegative [7,20].

Second-line antibody testing — Additional serologic testing is performed to increase diagnostic sensitivity for patients with clinical features of MG who do not have AChR antibodies. We typically assess such patients initially for MuSK antibodies because up to 10 percent of patients with MG have MuSK antibodies [9]. The diagnostic yield of LRP4 antibody testing is modest, positive in up to 1 percent of patients with MG [9]. We reserve testing for LRP4 antibodies for seronegative patients with an uncertain diagnosis after electrodiagnostic testing (algorithm 1). (See 'Electrodiagnostic confirmation for seronegative and atypical presentations' below.)

MuSK antibodies — MuSK is a receptor tyrosine kinase that mediates agrin-dependent AChR clustering and neuromuscular junction formation during development. MuSK antibodies are present in 38 to 50 percent of those with generalized MG who are AChR antibody negative [7,8,21-24] but are uncommon in ocular MG [25,26].

Patients with AChR-positive MG generally do not also have MuSK antibodies [8,21-23,27,28]. However, one group found that 11 percent of patients with AChR-positive MG did have antibodies to MuSK as well [29].

LRP4 antibodies — Antibodies against LRP4, an agrin receptor required for activation of MuSK and AChR clustering and neuromuscular junction formation, may be found in some patients with MG who do not have either AChR or MuSK antibodies. In a large cohort of 181 patients with confirmed MG who were seronegative for both AChR and MuSK antibodies, 13 percent were found to have antibodies to LRP4 [30]. In other studies, the frequency of LRP4-positive MG ranges from 2 to 50 percent among patients who are seronegative for both AChR and MuSK antibodies [9,30-32].

Other antibody testing — Autoantibodies to other neuromuscular junction proteins have also been reported in some patients with MG. These antibodies are not typically used for diagnosis but may be used in research settings to predict the presence of a thymoma and response to thymectomy [33-36].

●Striated muscle autoantibodies target heterogeneous striated muscle proteins. They are present in approximately 36 percent of patients with MG but in 80 percent of those with thymoma [37]. These antibodies may be a useful marker for thymoma in those patients between 20 and 50 years of age (ie, early-onset MG). In this cohort, thymoma can be found in 60 percent of patients with antistriated muscle antibodies but in less than 10 percent of those without these antibodies [37,38]. The false-positive rate (striational antibodies present without thymoma) is under 10 percent, but it rises to 50 percent in those 40 to 50 years of age or older.

●Titin is a large skeletal and cardiac muscle protein, and ryanodine is an intracellular protein within the sarcoplasmic reticulum. Autoantibodies to titin and/or ryanodine receptors may be found in some patients with MG. They have been associated with the presence of thymoma and may predict a more severe disease and an unsatisfactory outcome after thymectomy [35,36,39].

Further studies on these antibodies are needed to establish their value when added to the commercially available assays for AChR, MuSK, and LRP4 antibodies.

Classification by antibody status — Patients with AChR, MuSK, or LRP4 antibodies are classified as having seropositive MG. Other patients who do not have any of these autoantibodies are classified as having seronegative MG when diagnosed by electrodiagnostic testing. (See 'Electrodiagnostic confirmation for seronegative and atypical presentations' below.)

Autoantibodies in MG have been associated with specific clinical and epidemiologic features. In addition, serologic diagnosis may guide selection of immunosuppressive therapy.

●Seropositive MG

•AChR antibody-positive MG – AChR antibodies are present in approximately 85 percent of patients with generalized disease. Essentially all patients (98 to 100 percent) with MG and thymoma are seropositive for these antibodies [37,40]. The negative predictive value of thymoma in the absence of acetylcholine antibodies (binding) is high at 99.7 percent [37].

Thymic hyperplasia and thymoma is common in AChR antibody-positive MG. More than 75 percent of patients with AChR antibody-positive MG have thymic abnormalities, including thymic hyperplasia thymomas. (See 'Thymomas and other thymic masses' below.)

•MuSK antibody-positive MG – MuSK autoantibodies are found in approximately 8 percent of MG cases [7]. Patients with MuSK antibody-positive MG share most of the clinical manifestations of AChR-positive generalized MG. However, there is a female preponderance in MuSK antibody-positive MG, and patients are likelier to present with an oculobulbar form with diplopia, ptosis, and dysarthria [24,41-45]. Ocular symptoms are likelier to be symmetric and less likely to fluctuate than in patients with AChR-positive MG. In addition, MuSK-positive MG has also been associated with a restricted myopathic form with prominent respiratory and/or proximal weakness, especially in muscles of neck extension [21].

Thymic pathology is uncommon in patients with MuSK antibody-positive MG, unlike patients with AChR antibody-positive or seronegative MG [46-49].

Patients with MuSK-positive MG may be less responsive to anticholinesterase medications and less likely to be able to wean from glucocorticoid therapy. Rituximab is often used as first-line immunosuppressive therapy for MuSK-positive patients because symptoms may not improve with immunosuppressive therapies effective for other patients with AChR-positive or seronegative MG. (See "Chronic immunotherapy for myasthenia gravis", section on 'MuSK-positive MG'.)

•LRP4 antibody-positive MG – LRP4 or agrin antibody-positive MG has also been called "double-seronegative" MG, referring to patients who do not have either AChR or MuSK antibodies. LRP4-positive antibodies are found in approximately 1 percent of patients with MG [9]. There is a female predominance with LRP4 antibody-positive MG, and patients typically present with mild ocular symptoms [50]. However, at maximal disease severity, some patients with LRP4 antibodies may have more severe clinical symptoms than those without LRP4 antibodies. Most patients improve with standard immunosuppressive therapy [30].

As with MuSK-positive patients, there appears to be no association with thymoma or other thymic pathology, although data are limited [31].

●Seronegative MG – The term "seronegative MG," also called "antibody-negative MG," refers to the 6 to 10 percent of patients with MG who have negative standard assays for both AChR, MuSK, and LRP4 antibodies. The term was previously used only for those who were AChR antibody negative.

Seronegative MG is an autoimmune disorder with most of the same features as seropositive MG [20,24]. However, patients with seronegative MG are more likely to have purely ocular disease than those who are seropositive. The electrophysiologic findings are identical. Patients with seronegative MG respond in a similar fashion to pyridostigmine, plasma exchange, glucocorticoids, and immunosuppressive therapies, as well as thymectomy. There is also a trend for those with generalized seronegative MG to have a better response to immunosuppressive treatment [24].

ELECTRODIAGNOSTIC CONFIRMATION FOR SERONEGATIVE AND ATYPICAL PRESENTATIONS — Electrodiagnostic studies are performed to confirm the diagnosis of MG when initial serologic autoantibody testing is negative (algorithm 1). These studies may also be used for patients with atypical symptoms to exclude alternative diagnoses. Electrodiagnostic testing for MG includes nerve conduction studies with repetitive nerve stimulation (RNS) as well as electromyography (EMG), which may be performed with the single-fiber EMG (SFEMG) technique.

Nerve conduction testing with repetitive nerve stimulation — RNS testing involves repeated stimulation of a motor nerve to identify impairment in neuromuscular transmission by showing a progressive reduction in the amplitude of the compound muscle action potential (CMAP).

The test is performed by placing the recording electrode over the endplate region of a muscle and stimulating the motor nerve to that muscle. The muscles tested should be warm, and acetylcholinesterase inhibitors should be held for 12 hours before the study. Proximal muscles and clinically weak muscles should be tested in addition to distal muscles. The nerve is electrically stimulated 6 to 10 times at low rates (2 or 3 Hz). The CMAP amplitude is recorded from the electrode over the muscle after electrical stimulation of the nerve. In normal muscles, there is no change in CMAP amplitude with RNS. In MG, there may be a progressive decline in the CMAP amplitude with the first four to five stimuli (a decremental response).

An RNS study is considered positive (ie, abnormal) if the decrement is greater than 10 percent (waveform 1).

Electrical stimulation is also performed after exercise to identify postactivation facilitation (improvement) in CMAP amplitude. In the exercise protocol, the patient is asked to exercise the muscle maximally for 30 to 60 seconds. A train of stimuli is performed immediately after exercise. A repair of the CMAP decremental response (a smaller percent decrement compared with the decrement seen at rest) indicates postexercise or postactivation facilitation (waveform 2). An additional train of stimuli is delivered at one, three, and five minutes after exercise. This delayed stimulation may result in a larger decrement than seen at rest, termed postexercise or postactivation exhaustion. The exercise protocol may increase the sensitivity of RNS by an additional 5 to 10 percent.

RNS testing is positive in approximately 75 to 80 percent of patients with generalized MG if recordings are made from proximal (usually trapezius and orbicularis oculi), as well as distal muscles (table 1) [6,51,52]. Sensitivity improves with more severe weakness and may be greater than 90 percent in patients with myasthenic crisis [53,54]. By contrast, the sensitivity of RNS is much lower (eg, 15 to 45 percent) in patients with ocular MG.

A decremental response is not specific for MG. Decrements may be seen in other disorders of neuromuscular transmission (Lambert-Eaton myasthenic syndrome or botulism) and motor neuron disease. These disorders should not cause electrodiagnostic confusion when combined with studies looking for presynaptic disorders of neuromuscular transmission and standard needle EMG.

RNS studies are discussed in greater detail separately. (See "Electrodiagnostic evaluation of the neuromuscular junction", section on 'Repetitive nerve stimulation'.)

Electromyography — EMG evaluates the electrical activity of muscle both at rest and with voluntary muscle contraction. EMG is performed as a component of routine electrodiagnostic testing to help localize impairment of motor function to the nerve, neuromuscular junction, or muscle. Typically, multiple body regions including several limb and bulbar muscles are tested to exclude alternative disorders as a cause of the weakness, such as motor neuron disease and myopathic processes. However, the specific protocol varies by patient symptoms and signs. (See "Overview of electromyography".)

Conditions that may mimic the clinical features of MG are discussed elsewhere. (See "Differential diagnosis of myasthenia gravis".)

Single-fiber electromyography — SFEMG is the most sensitive diagnostic test for MG (table 1). SFEMG is performed with a specialized needle electrode that allows simultaneous recording of the action potentials of two muscle fibers innervated by the same motor axon. The variability in time of the second action potential relative to the first is called "jitter." Increased jitter occurs when neuromuscular transmission is impaired because the physiologic excess (safety factor) in the amount of neurotransmitter required to produce an action potential is reduced. A reduced safety factor leads to variable timing of nerve impulse transmission and increased jitter in MG.

SFEMG is more technically demanding than RNS and is less widely available than other electrodiagnostic techniques. To maximize the sensitivity, both a limb and facial muscle may be studied. SFEMG is positive in greater than 90 percent of those with generalized MG [6,52]. In ocular MG, the diagnostic sensitivity of SFEMG ranges from 73 to 95 percent if a facial muscle is studied [1,55]. In a prospective, single-blinded study of 100 patients with clinically diagnosed MG (mostly ocular or mild generalized), SFEMG of a single facial muscle (the orbicularis oculi) yielded a sensitivity and specificity of 98 and 70 percent, respectively [56].

Abnormal jitter is not specific for MG. Other disorders that reduce the safety factor in neuromuscular transmission and produce jitter include motor neuron disease, polymyositis, peripheral neuropathy, and Lambert-Eaton myasthenic syndrome. SFEMG should be performed with caution, or not at all, in those patients who have received botulinum injections for migraine, dystonia, or other indications. Abnormal SFEMG values (increased jitter) can be seen for up to a year, even in muscles distant from the injection site [57].

SFEMG is discussed in greater detail separately. (See "Electrodiagnostic evaluation of the neuromuscular junction", section on 'Single-fiber electromyography'.)

ADDITIONAL TESTING FOR ATYPICAL PRESENTATIONS — Additional studies performed to exclude other diagnoses are typically reserved for selected patients with atypical clinical features.

●Magnetic resonance imaging (MRI) of the brain may be performed for patients with nonfluctuating ocular or bulbar symptoms to exclude structural lesions such as tumor or stroke.

●Computed tomography (CT) or ultrasonography of the orbits may be performed for patients with isolated nonfluctuating diplopia to evaluate for orbital mass lesions, including edema associated with thyroid ophthalmopathy.

●Lumbar puncture for cerebrospinal fluid analysis may be performed for patients with multiple cranial nerve abnormalities to assess for inflammation or malignancy.

The differential diagnosis of MG is discussed in detail separately. (See "Differential diagnosis of myasthenia gravis".)

EVALUATION FOR ASSOCIATED CONDITIONS — All patients diagnosed with MG should be evaluated for associated conditions such as thymomas or other autoimmune conditions. Thymectomy may be indicated for many patients with MG, and coexisting autoimmune conditions may require further evaluation and additional management strategies.

Thymomas and other thymic masses — For seronegative and most seropositive patients with MG, we recommend chest CT or MRI to define anterior mediastinal anatomy and to evaluate for a thymoma. Therapeutic thymectomy is indicated for patients with MG and a thymoma as well as selected (nonthymomatous) patients with seropositive or seronegative MG (algorithm 2). Patients with muscle-specific tyrosine kinase (MuSK)-positive MG do not typically require chest imaging because thymic abnormalities and thymomas are not associated with MuSK-positive MG, and thymectomy has not been shown to be effective in this group [58]. (See "Role of thymectomy in patients with myasthenia gravis".)

We perform either CT or MRI of the mediastinum to evaluate the thymus for patients with MG. CT and MRI reliably detect thymoma but do not effectively distinguish between thymic hyperplasia and normal tissue in patients with MG [59,60].

Approximately 15 percent of patients with MG have thymomas and nearly 40 percent of patients with thymoma have MG [61-63]. More than 75 percent of patients with acetylcholine receptor (AChR) antibody-positive MG have thymic abnormalities. For those with thymic pathology, thymic hyperplasia is most common (85 percent), but other thymic tumors (primarily thymoma) are present in up to 15 percent [64]. The thymic tumors are usually noninvasive cortical thymomas, but invasive thymic carcinoma can also occur. Thymomas are uncommon in the absence of AChR antibodies [37]. (See "Clinical presentation and management of thymoma and thymic carcinoma".)

Thymic pathology in MG is also associated with autoimmune thyroid disease and the risk for other neoplastic disorders [61]. MG has been associated with extrathymic tumors, such as small-cell lung cancer and Hodgkin lymphoma [65-68]. It is uncertain from these studies whether this co-occurrence represents a true association. The data do not warrant an extensive search for malignancy other than thymoma in the routine evaluation of MG, even in older patients.

Associated autoimmune conditions — We suggest obtaining thyroid function testing in all patients with MG to assess for autoimmune thyroid conditions. Testing for other autoimmune conditions is generally reserved for patients with a suggestive clinical history or findings on clinical examination, such as rash or arthritis.

Autoimmune thyroid disease occurs in 3 to 10 percent of patients with MG. Autoimmune rheumatic disorders, including Sjögren's disease, rheumatoid arthritis, and systemic lupus erythematosus (SLE), also occur with increased frequency in patients with MG compared with age- and sex-matched patients without MG [69]. The reported incidence of a comorbid rheumatic disorder ranges from 1.25 to as high as 8 percent [69-73]. (See "Pathogenesis of Hashimoto's thyroiditis (chronic autoimmune thyroiditis)" and "Neurologic manifestations of Sjögren's disease" and "Overview of the systemic and nonarticular manifestations of rheumatoid arthritis" and "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults", section on 'Neurologic and neuropsychiatric involvement'.)

Some studies have reported an excess risk of autoimmune disorders in patients with MG who have undergone thymectomy for MG [69]. Whether thymectomy itself alters risk is not known, and data are conflicting [69,70,74]. Further studies are needed to better understand whether specific therapies for MG have an impact on the incidence of comorbid autoimmune disorders.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Myasthenia gravis" and "Society guideline links: Thymomas and thymic carcinomas".)

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^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics 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 education: Myasthenia gravis (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Clinical testing – MG should be suspected in patients with fatigable muscle weakness, including those with isolated ptosis and/or diplopia. Specific examination techniques, such as the ice pack test, may be used to help localize motor weakness to the neuromuscular junction. The ice pack test involves direct cooling of the eyelid to assess for improvement in ptosis. (See 'Clinical testing' above.)

●Serologic diagnosis – For most patients with clinical features of MG, the diagnosis is confirmed by the presence of autoantibodies against the acetylcholine receptor (AChR) or against other muscle receptor-associated proteins (eg, muscle-specific tyrosine kinase [MuSK] or low-density lipoprotein receptor-related protein 4 [LRP4]) (algorithm 1). (See 'Serologic diagnosis' above.)

•An immunologic assay to detect the presence of circulating AChR antibodies should be the initial laboratory test performed to confirm the diagnosis of MG. AChR antibodies are found in up to 90 percent of patients with generalized MG (table 1). (See 'Acetylcholine receptor antibodies' above.)

•Serologic testing for MuSK and LRP4 antibodies may be performed for patients with clinical features of MG who do not have AChR antibodies. (See 'Second-line antibody testing' above.)

●Electrodiagnostic confirmation – Electrodiagnostic studies are performed to confirm the diagnosis of MG when initial serologic autoantibody testing is negative and to exclude alternative diagnoses for patients with atypical symptoms (algorithm 1). Electrodiagnostic testing for MG includes nerve conduction studies with repetitive nerve stimulation (RNS) as well as electromyography (EMG), which may be performed with the single-fiber EMG (SFEMG) technique. (See 'Electrodiagnostic confirmation for seronegative and atypical presentations' above.)

•RNS studies can identify impairment of neuromuscular transmission when repeated stimulation of a motor nerve shows a progressive reduction in the amplitude of the compound muscle action potential (CMAP) (waveform 1). (See 'Nerve conduction testing with repetitive nerve stimulation' above.)

•SFEMG is performed with a specialized needle electrode that can show variability in time between the action potentials of two muscle fibers innervated by the same motor axon to indicate impairment in neuromuscular transmission. (See 'Single-fiber electromyography' above.)

●Additional evaluation

•Testing to exclude alternative diagnoses – Additional diagnostic testing is typically reserved for selected patients with atypical clinical features to exclude other diseases in the differential diagnosis of MG. Testing may include brain MRI, CT or ultrasound of the orbits, and/or lumbar puncture for cerebrospinal fluid analysis. (See 'Additional testing for atypical presentations' above.)

•Testing for associated conditions – All patients diagnosed with MG should be evaluated for associated conditions such as thymomas or other autoimmune conditions. Thymectomy is indicated for patients with MG and a thymoma as well as selected (nonthymomatous) patients with seropositive or seronegative MG (algorithm 2). In addition, we suggest screening all patients with MG for autoimmune thyroid disease. (See 'Evaluation for associated conditions' above.)