Seronegative MG Resource Center | MGFA
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Seronegative MG Resource Center

You may have questions about what seronegative myasthenia gravis (MG) is, how to diagnose it, and how treatment might differ from antibody-positive MG. This resource center is a helpful, high-level overview for patients and caregivers, and provides diagnostic and treatment resources for medical providers. The references section provides detailed information from academic sources about the topics discussed in the Seronegative MG Resource Center. We will continue to add resources, articles, information, and patient stories to provide a robust set of materials. (Thank you to contributors Cheri Heitman-Higgason, Zachary McCallum, and Leslie Edwards for their work on this resource).

Jump to a section:

What is Seronegative Myasthenia Gravis?   |     What Causes Seronegative Myasthenia Gravis?   |   What Are Symptoms of Seronegative Myasthenia Gravis?   |   How is Seronegative Myasthenia Gravis Diagnosed?   |   What Treatments are Available for Seronegative Myasthenia Gravis?   |   How Can I Help My Doctor Help Me?   |   First-hand Perspective of a Seronegative MG Patient   |   Helpful Links and Resources   |   References

 

What is Seronegative Myasthenia Gravis?

The majority of people diagnosed with myasthenia gravis (MG) have acetylcholine receptor (AChR) or muscle-specific receptor tyrosine kinase (MuSK) antibodies in their blood. If your blood does not contain these antibodies, you can still have MG if you meet certain diagnostic criteria. This is called seronegative myasthenia gravis (SNMG). It is thought that approximately 10% of MG patients may be seronegative. The actual number could be higher, as many seronegative MG patients may go undiagnosed.

In those patients who have no detectable antibodies, the diagnosis is based on clinical presentation, which includes a thorough review of the medical history and an exam by a qualified physician, electrodiagnostic findings (which may also be negative in some cases), and response to typical MG treatments such as cholinesterase inhibitors. Seronegative MG is poorly understood, but more is being done to research and develop better treatments for this “Rare-of-the Rare” disease.

 

What Causes Seronegative Myasthenia Gravis?

Myasthenia gravis is caused by autoantibodies formed by your immune system that attack the receptor sites between nerves and muscles. This results in fewer nerve signals reaching the muscles, which causes muscle weakness.

The process is no different in seronegative MG. In SNMG, however, the antibodies are not detectable with currently available testing, or there are different antibodies present that have not yet been discovered.

 

The main antibodies that are currently tested for are AChR and MuSK. The newest antibody found to cause MG is LRP4, which can now also be tested for with a simple blood test. Additionally, a more sensitive type of blood test called a cell-based assay is becoming more commercially available. This newer test may be able to detect AChR antibodies in patients who were previously thought to be seronegative. In a 2022 study published in the Journal of Neuroimmunology, 18.2% of seronegative patients tested positive for AChR antibodies using cell-based assay testing.

 

In terms of seronegative MG, clinical research is underway to determine whether seronegative MG symptoms could be caused by antibodies for other proteins such as agrin, as-yet to be determined antibodies, or if other biomarkers could be used for testing. If so, a more reliable blood test could be developed to help with diagnosis. If you’re interested in participating in a clinical trial, visit our research page.

 

What Are Symptoms of Seronegative Myasthenia Gravis?

Symptoms of seronegative MG present similarly to antibody positive MG. This means it can be either ocular or generalized, with variable symptoms ranging from mild to severe. MG affects the voluntary muscles of the body. Symptoms vary between individuals, and these symptoms can come and go depending on the level of muscle fatigue. MG symptoms are called fatigable because the weakness worsens with repetitive activity.

Common symptoms include:

  • ptosis (drooping of one or both eyelids)

  • blurred or double vision

  • facial muscle weakness, which can cause a mask-like appearance and make a smile look like a snarl

  • difficulty talking

  • difficulty chewing and swallowing

  • difficulty breathing

  • weakness of the neck and limbs

A number of factors may make MG symptoms worse. They include:

  • Infections of any kind

  • Extreme heat, cold, or humidity

  • Poor sleep

  • Increased activity level

  • Repetitive activity

  • Menstruation

  • Physical or emotional stress

  • Thyroid dysfunction

  • Low potassium level

  • Some medications (see Cautionary Drugs for MG Patients)

  • Missed dose(s) of MG medications

 

How is Seronegative Myasthenia Gravis Diagnosed?

Diagnosing seronegative myasthenia gravis can be challenging. Your physician may think you have myasthenia gravis, but without AChR, MuSK or LRP4 antibodies they will need to rule out other possible diagnoses. Being tested for all available MG antibodies is important, as some treatments are antibody specific. Cell-based assays for MG antibodies are becoming more available and are more sensitive.

Stroke, MS (multiple sclerosis), LEMS (Lambert-Eaton myasthenic syndrome), CMS (congenital myasthenic syndromes), and ALS (amyotrophic lateral sclerosis) are some of the diseases with symptoms that can mimic MG. Before being diagnosed with seronegative MG, it is important to be tested for other possible diseases to rule them out. This could involve more lab testing, MRI of brain and spine, lumbar puncture, muscle biopsy, and other tests.

Your physician can assess your symptoms in different ways, including:

  • Thorough review of the patient’s medical history

    • The patient’s description of their history and symptoms in their own words

    • Medical chart notes, lab results, imaging studies and other material from previous medical exams

  • Physical and neurological exams to evaluate clinical signs. MG generally presents with fatigable weakness that worsens with use of a muscle and improves with rest, and is variable in nature

    • Upward and lateral gaze tests to evaluate ptosis and double vision

    • Limb strength tests against resistance—for example, your physician may ask you to try to raise your leg from the hip while they push down on your knee

    • Repetitive testing of muscles to evaluate for quick muscle fatigue—for example, strength testing performed 3-4 times or repeated sit-to-stand testing

    • Neck flexion and extension against resistance

    • Tongue strength

    • Listening to your speech to evaluate nasality and slurring

  • Electrodiagnostic testing. Specialized testing can often only be accessed through larger medical centers and academic research hospitals. A neurologist with a neuromuscular specialty may be necessary to provide these more specialized tests

    • The two main types of electrodiagnostic testing used in diagnosing MG are repetitive nerve stimulation (RNS) and single fiber electromyography (SFEMG). Your physician may perform one or both of these tests

    • Repetitive nerve stimulation (RNS): Your physician will stimulate some of your nerves with an electrode. The response should be the same with each stimulation, but with MG each successive stimulation gets a smaller nerve response. Typically, RNS is done first. If it shows a pattern consistent with MG, no further testing may be required

    • Single Fiber EMG (SFEMG): Your physician will put a very thin needle into muscle tissue to stimulate a single branch of the motor nerve with an electrical current. Targeting that nerve should lead to a cascade of muscle activation. For patients with myasthenia, the muscle response will be delayed

      • SFEMG is a more difficult test to perform than RNS and is often only available at larger medical centers and academic research hospitals. Accurate results depend on many factors including:

        • Equipment used

        • Skill and expertise of the person performing the test

        • Room and patient body temperatures

        • Choice of muscles tested and whether they are clinically weak at the time of testing

        • Testing more than one muscle

        • Whether or not certain medications were held

        • Treatments the patient is on that may affect the symptoms of myasthenia gravis, including immunosuppressants

    • With all electrodiagnostic testing, it is important to check with your physician to see if any medications need to be held prior to testing

    • It is common to hold Mestinon (pyridostigmine bromide) for 24–72 hours if the patient’s condition allows and upon physician’s recommendation

    • Sometimes it is recommended to hold caffeine as well (including coffee, tea, soda, and chocolate) because caffeine can affect the neuromuscular junction by acting as an acetylcholinesterase inhibitor (similar to Mestinon)

    • The temperature of the skin over the area being tested should be close to 35°C (95°F). Testing in a warm room or using a heat lamp can help to get accurate results

    • It is important to choose a muscle that is clinically weak at the time of the testing

    • Sometimes all electrodiagnostic testing can be negative and a patient can still have seronegative myasthenia gravis

  • Ice pack test

    • The ice pack test for myasthenia gravis is a simple and inexpensive bedside test if the patient presents with ptosis. This test involves measuring the eyelid opening, placing an ice pack over the eye for 2–5 minutes, then remeasuring the eyelid opening

    • The ice pack test is positive if there is an improvement of ptosis of 2 mm or more

    • The ice pack test has a similar diagnostic accuracy for ocular myasthenia gravis (OMG) as SFEMG in patients who present with ptosis

  • Edrophonium (Tensilon) test. This test, once common, is rarely used now because of the risk of serious and possibly life-threatening side effects. When it is performed, this test involves giving the patient an intravenous injection of a short-acting cholinesterase inhibitor and evaluating the response. Because it carries significant risk, this test must be performed in a well-controlled medical environment with emergency management facilities available

  • Pulmonary Function Testing (PFT) may be ordered to assess breathing function and assist with diagnosis

    • PFT typically involves breathing into a device to evaluate lung function, capacity, and strength of the respiratory muscles

    • It is important to include MIP (maximum inspiratory pressure) and MEP (maximum expiratory pressure) to adequately assess the strength of the muscles used for breathing

  • A CT scan of the chest is commonly performed to look for thymoma. Thymomas are less common in seronegative patients but can be present

  • A trial of medications commonly used to treat myasthenia gravis may be given

    • Mestinon (pyridostigmine bromide), an acetylcholinesterase inhibitor, is the most commonly trialed medication—but not all MG patients respond to Mestinon

    • Sometimes a trial of other medications such as corticosteroids (i.e., prednisone, etc.) or intravenous immunoglobulin (IVIg) may also be used

    • While on a medication trial, keeping a symptom diary is very important to assist with diagnosis. A symptom diary should include

      • Symptoms the patient is experiencing

      • Timing of medication dose(s)

      • Which, if any, symptoms are helped by the medication

      • How soon symptom improvement occurs after a medication dose

      • How quickly symptoms return

      • Any other factors that improve or worsen your symptoms

Results from some of these tests can be negative or inconclusive, even for someone who is experiencing symptoms of MG. A clinician skilled in recognizing and distinguishing MG from other conditions is important in determining a proper diagnosis.

 

What Treatments are Available for Seronegative Myasthenia Gravis?

Seronegative MG patients often find it difficult to receive treatments. Even when they do, they may not receive adequate treatment to maximize symptom control. Because SNMG is more difficult to diagnose, delays in diagnosis may result in a delay in receiving effective treatment. The sooner MG is treated, the better the chances are for improvement.

Most of the newer treatments specifically for MG on the market today are only FDA approved for patients who are AChR antibody positive. They include:

  • Soliris

  • Ultomiris

  • Vyvgart

  • Zilucoplan

Some SNMG patients have been able to get off-label approval for these newer medications through special approval by their insurance companies.


Although those newer treatments are typically only available for AChR-positive MG patients, there are still many options for seronegative patients. They include:

  • Mestinon

  • Corticosteroids (i.e., prednisone, etc.)

  • Intravenous immunoglobulin (IVIg) or subcutaneous immunoglobulin (SCIg)

  • Plasmapheresis (PLEX)

  • Immunosuppressant Therapy

    • CellCept

    • Imuran

    • Methotrexate

    • Tacrolimus

    • Rituximab

    • Others

  • Thymectomy

    • Although thymectomy was previously recommended for seropositive patients only, according to the most recent edition of the International Consensus for Management of Myasthenia Gravis, thymectomy may be considered for seronegative MG patients with or without evidence of an abnormality in the thymus gland shown on scans

 

How Can I Help My Doctor Help Me? 

A good doctor-patient relationship is key to good results. You can help your doctor get a better picture of what you are experiencing by bringing:

  • A concise summary of your medical history, symptoms, factors that improve or worsen them, and how this affects your daily life

  • A list of your questions and concerns

  • Printouts of previous test results

  • CDs of imaging studies previously performed

  • Photos or videos of yourself showing symptoms

  • A friend or family member who can tell the physician their observations

During your appointment:

  • Take notes so you remember what the physician said

  • Some people, with their physician’s permission, make an audio recording of their appointment

  • Don’t be afraid to advocate for yourself

  • Remember that you and your physician are equal partners on a team

Some additional advice from a seronegative patient who has journeyed far and experienced much on the path to diagnosis and proper treatment:

  • Never give up!

  • Make sure you have had all the testing: AChR, MuSK, LRP4, repetitive nerve stimulation (RNS), single-fiber electromyography (SFEMG), and chest CT (to name a few) and that you obtain and keep a record of all results

  • If your condition allows, have blood testing and electrodiagnostic testing done prior to starting immunosuppressant medications or disease-modifying treatments. These treatments could potentially alter the antibodies in your blood and interfere with test results

  • Discuss testing for other conditions and rare diseases with your provider. Many rare diseases have similar symptoms but different treatments. Other conditions and rare diseases (including LEMS and CMS) can be diagnosed with additional lab tests, genetic testing, imaging like MRI of the brain and spine, lumbar puncture, etc.

  • Be open to other possibilities in order to make every attempt to get to the root of the problem, whatever it may be

  • Remember not to demand a particular diagnosis, but to work together with your provider

  • Be aware that you may have more than one condition, making diagnosis more challenging

  • If you don’t feel you are connecting with one provider, getting a second opinion may be helpful

  • Be open-minded with your new provider. Go to the appointment prepared with a list of questions and concerns. A fresh perspective can help you get a diagnosis

  • Since symptoms with MG are variable, document your symptoms clearly and include aggravating and alleviating factors. Use of a written diary as well as photos and videos may be helpful

 

First-hand Perspective of a Seronegative MG Patient

What were the first symptoms you noticed and when did you first notice them?

The first symptoms I noticed were not unlike the first symptoms that seropositive individuals experience. Seronegative MG typically has the same general symptoms as seropositive MG and has a similar response to treatment. I was diagnosed between 2015–2016 and reconfirmed in 2017. Looking back, I had symptoms for at least 10 years prior. I thought they were unrelated, and since MG symptoms fluctuate, it was very difficult to put them together until the symptoms became much worse. My symptoms included:

  1. Ocular: I had intermittent eye drooping, vision changes that progressed from blurry vision to overlapping and then double vision, along with abnormal eye movements. When I tried to read, I noticed I would close one eye to eliminate the double vision, but I had no idea why.

  2. Shortness of Breath: Prior to 2015, I was exercising regularly at a good aerobic level. Gradually, that changed. I was able to do less and less until my shortness of breath made it impossible to exercise at all. As a cardio-pulmonary R.N. of many years, this made no sense to me. Basic pulmonary and cardiac testing was normal. I became SOB with very little activity. Sometimes my pulmonary patients would tell me I needed pulmonary rehab more than they did when they noticed my shortness of breath. There were times at night that my breathing became so shallow, my husband could not even feel the rise and fall of my chest.

  3. Activity: My activity level gradually decreased until I eliminated every activity except work. I could not tolerate much activity and the fatigue afterwards was debilitating. I had to lean against the shower wall while showering and lie down afterwards. Getting to work on time became extremely difficult. Sitting up for 30 minutes at a time was difficult due to core muscle fatigue/weakness. While working, I propped myself up with pillows whenever I was at my desk.  Eventually, I could no longer climb the stairs at work and my legs felt like jello when I went down stairs. Sometimes my legs quit working, such as when I tried to ride a bike. If I rested a few minutes, I could then go a few minutes more, but the rest periods never "fixed" my ability to be active. Activities that required use of my arms were also difficult. I could hold something close to my body, but any activity with my arms raised or out to the side was much harder. This impacted my personal grooming, driving, etc. I used to say that my body felt like it was encased in concrete and buried in sand. The only relief was to lie down with my head, neck, and arms supported. After lying down for hours, I could be up for 15 to 30 minutes and then the symptoms all started again.

  4. Speech, Chewing, and Swallowing: I first noticed I was choking easily on certain foods and certain foods were difficult to chew. I learned to avoid problematic foods and drank 4-6 glasses of fluids with each meal to get food to go down, basically "blind swallowing”, which is not safe. When I was weaker, doing more talking, or by evening, talking became more difficult. Hoarseness and slurring of words were common.

 

Helpful Links and Resources

Connect with Others

Understanding and Managing MG

Additional Information from the MGFA

MG Resources and Emergency Information for Medical Professionals

 

References

The references section provides detailed information from academic sources about the topics discussed in the Seronegative MG Resource Center.

Autoantibodies in SNMG

“Autoantibody profile in myasthenia gravis patients with a refractory phase” Veltsista et al., Muscle & Nerve, May 2022, Volume 65, Issue 5: pages 607-611; doi:10.1002/mus.27521.

In this study, patients with refractory MG were more likely than those with nonrefractory MG to be DSN; and refractory DSNMG patients had worse MGFA classes in their recent visit compared with anti-AChR positive refractory patients. Refractory DSNMG patients may represent a distinct group that requires more individualized and targeted treatment approaches.

 

“Clinical Characteristics of Patients With Double-Seronegative Myasthenia Gravis and Antibodies to Cortactin” Cortés-Vicente et al., JAMA Neurology, 2016, Volume 73, Issue 9: pages 1099-1104; doi:10.1001/jamaneurol.2016.2032.

In this study, patients with cortactin antibodies and dSNMG had an ocular or mild generalized phenotype of MG. Including the detection of cortactin antibodies in the routine diagnosis of dSNMG may be helpful in ocular MG.

 

“The clinical need for clustered AChR cell-based assay testing of seronegative MG” Masi et al., Journal of Neuroimmunology, June 2022, Volume 367: 577850; doi:10.1016/j.jneuroim.2022.577850.

Trial eligibility in myasthenia gravis (MG) remains largely dependent on a positive autoantibody serostatus. This significantly hinders seronegative MG (SNMG) patients from receiving potentially beneficial new treatments. In a subset of SNMG patients, acetylcholine receptor (AChR) autoantibodies are detectable by a clustered AChR cell-based assay (CBA). Of 99 SNMG patients from two academic U.S. centers, 18 (18.2%) tested positive by this assay. Autoantibody positivity was further validated in 17/18 patients. In a complementary experiment, circulating AChR-specific B cells were identified in a CBA-positive SNMG patient. These findings corroborate the clinical need for clustered AChR CBA testing when evaluating SNMG patients.

 

Diagnosing SNMG

“The Duke myasthenia gravis clinic registry I. Description and demographics” Sanders et al., Muscle & Nerve, February 2021, Volume 63, Issue 2: pages 209-216; doi:10.1002/mus.27120.

Eyelid ptosis or diplopia are the first symptoms noted by most patients with MG, and this was the case in almost two-thirds of the cohort patients. MG was diagnosed or suspected by the first clinician in only half the cohort patients. The initial diagnosis given to explain MG symptoms is a reflection of not only the nature of the symptoms, but also the bias of the observer. Thus, vascular disease was suspected more often in men, who frequently develop MG at an age when cerebrovascular disease is common. Psychosomatic disease was suspected more often in women; this has long been true, as exemplified by Oosterhuis's observation that, among his MG patients, 8% of women and no men had been referred to a psychiatry clinic before the diagnosis was made.

 “The Duke myasthenia gravis clinic registry II. Analysis of outcomes” Sanders et al., Muscle & Nerve, April 2021, Volume 67, Issue 4: pages 291-296; doi:10.1002/mus.27794.

The diagnosis of autoimmune MG was determined by the following criteria: 1. Acetylcholine receptor antibodies (AChR-Abs) or muscle-specific tyrosine kinase (MuSK) antibodies were present; or 2. Patients were normal at birth and later developed fatigable weakness; and 3. Abnormal neuromuscular transmission (NMT) was demonstrated by a decrementing response to repetitive nerve stimulation, increased jitter on single-fiber EMG (SFEMG), or improvement after administration of an acetylcholinesterase inhibitor: pyridostigmine, neostigmine, or edrophonium; and 4. Patients without AChR or MuSK antibodies had unequivocal and sustained improvement after immunomodulatory or immunosuppressive (IS) treatment.

Among the 367 cohort patients, 72% achieved TG [treatment goal] (median time less than 2 years). A greater proportion of patients with AChR-Abs and thymectomy achieved TG and they did so sooner than patients without these antibodies or thymectomy.

 

The Ice Pack Test

“Comparison of ice pack test and single-fiber EMG diagnostic accuracy in patients referred for myasthenic ptosis” Giannoccaro et al., Neurology, September 2020, Volume 95, Issue 13: e1800-e1806; doi:10.1212/WNL.0000000000010619.

IPT and SF-EMG have similar diagnostic accuracy in patients with OM presenting with ptosis.

“Ice pack test—an useful bedside test to diagnose myasthenia gravis” Cheo et al., QJM: An International Journal of Medicine, May 2019, Volume 112, Issue 5: pages 381–382; doi:10.1093/qjmed/hcy284.

Ice pack test derived from clinical observations that cold improves myasthenia symptoms whereas heat worsens it. Neuromuscular transmission improves at lower temperature. These observations were reported by Simpson and Guttman in the past. The exact mechanism behind this is still uncertain. Postulated theories include cold enhanced release of acetylcholine, inhibition of acetylcholinesterase activity and/or improved acetylcholine receptor sensitization.

Ice pack test can be done by taking baseline eyelid measurement. Ice pack is then applied for 2–5 min and the eyelid is re-measured after that. If there is improvement of 2 mm or more, it’s considered a positive test. The test is thought to be sensitive and specific for myasthenia gravis, where it has no effect on ptosis from other causes. The reported sensitivity is up to 80%. In conclusion, ice pack test is a very useful bedside test when myasthenia gravis is suspected as it’s safe, cheap and easily performed.

 

RNS and SFEMG

“Guidelines for single fiber EMG” Sanders et al., Clinical Neurophysiology, August 2019, Volume 130, Issue 8: pages 1417-1439; doi:10.1016/j.clinph.2019.04.005.

In MG patients who improve after immunotherapy, jitter typically continues to fall toward normal as long as adequate immunotherapy is continued; deviation from this pattern suggests that treatment may not be adequate. Exceptionally, all jitter parameters improve during clinical remission (Emeryk et al., 1985, Sanders and Howard, 1986, Kostera-Pruszczyk et al., 2002) …

Another factor to be considered is the specific muscles and number of muscles in which jitter was tested. Most studies report the results of jitter testing in the same one or two muscles in all patients, even though no one muscle or combination of muscles is more likely to be abnormal in all MG patients.

No one muscle is more abnormal or more likely to be abnormal in every MG patient. In patients with mild disease or weakness in only a few muscles, it is particularly important to test a symptomatic muscle.

 

“Practice Parameter for RNS and Single Fiber EMG Eval of Adults with Suspected MG” Tan et al., American Association of Neuromuscular & Electrodiagnostic Testing, reaffirmed October 2015. (PDF)

Skin temperature over the recording site should be maintained as close to 35°C as possible.

 

It is important that limb temperature be monitored because sensory and motor nerve conductions are temperature dependent.

 

In 1974, Borenstein and Desmedt examined the effect of temperature on 30 patients with MG. They cited the example of a patient with an 11% percent decrement of the adductor pollicis muscle using 3 Hz RNS at 31°C. The decrement increased to 44% at 36°C. When they performed RNS of the ADQ at 31°C, there was a 10% decrement in amplitude. The decrement increased to a 64% decrement when warmed to 36°C. The opposite effect occurred with cooling. At 34.2°C, RNS of the facial nerve demonstrated a decrement of 25%. It decreased to normal limits (4%) when cooled by 5°C to 29.2°C. In 1975, Borenstein and Desmedt then examined the effect of local cooling in MG on RNS. They found that a reduction of the intramuscular temperature from 35°C to 28°C increased the CMAP size of the ADQ, twitch force, and tetany force at 10 and 20 Hz. They suggested that false negatives in RNS testing of MG may be due to insufficient warming of muscles.

In 1977, Ricker and colleagues also examined the effect of local cooling in 28 patients with MG. It was found that the amplitude of the adductor pollicis motor action potential increased in size at lower intramuscular temperatures. The ulnar nerve was stimulated at 3 Hz for 2 s, then 50 Hz for 1.5 s. With mild cooling, there was an increase in tetanic force. With severe intramuscular cooling to 18°C to 22°C, the tetanic force was lower.

 

“Single fiber EMG: A review” Selvan, VA., Annals of Indian Academy of Neurology, 2011 Jan-Mar, Volume 14, Issue 1: pages 64–67; doi:10.4103/0972-2327.78058.

No one muscle is more abnormal or more likely to be abnormal in every MG patient. In patients with mild disease or weakness in only a few muscles, it is particularly important to test a symptomatic muscle.

 

Caffeine and Cholinesterase Inhibitors May Affect Results of Testing

“Caffeine Inhibits Acetylcholinesterase, But Not Butyrylcholinesterase” Pohanka M, Dobes P, International Journal of Molecular Sciences, May 2013, Volume 14, Issue 5: pages 9873-9882; doi:10.3390/ijms14059873.

Caffeine is a simply available drug that has been known for a long time and by many cultures. Despite a lot of work on the identification of caffeine's effect in the body, some pathways remain undiscovered. In the present work, we proved that caffeine can act as a non-competitive inhibitor of AChE in the body.

“The effect of cholinesterase inhibitors on SFEMG in myasthenia gravis” Massey et al., Muscle & Nerve, February 1989, Volume 12, Issue 2: pages 154-155; doi:10.1002/mus.880120211.

We report four patients with myasthenia gravis (MG) in whom single-fiber electromyography (SFEMG) jitter measurements were normal in some muscles while they were taking pyridostigmine and became abnormal 2–14 days after the medication was discontinued. When the abnormality of neuromuscular transmission in MG is mild, cholinesterase inhibitors may mask the findings of increased jitter on SFEMG.

 

“Inhibition of acetylcholinesterase by caffeine, anabasine, methyl pyrrolidine and their derivatives” Karadsheh et al., Toxicology Letters, March 1991, Volume 55, Issue 3: pages 335-342; doi:10.1016/0378-4274(91)90015-x.

 

Immune Therapy May Affect Results of Testing

“Guidelines for single fiber EMG” Sanders et al., Clinical Neurophysiology, August 2019, Volume 130, Issue 8: pages 1417-1439; doi:10.1016/j.clinph.2019.04.005.

All of these parameters improved in patients who had significant improvement in strength after treatment with prednisone or plasma exchange and changes in jitter were less marked in patients who had only a slight response to treatment. There was a strong correlation between overall clinical change and a change of at least 10% in mean jitter in any muscle. 


In a retrospective study of patients treated with cyclosporine, the MCD fell more than 10% from the pretreatment value in all patients. Jitter has been measured in several therapeutic trials in MG. In a pilot trial of mycophenolate mofetil (MMF), the mean MCD was significantly lower in patients receiving MMF vs those receiving placebo. In another trial of MMF, there was a significant correlation between change in all jitter parameters and change in clinical outcome measures.


Serial jitter studies in a patient with refractory MG who received eculizumab in a prospective trial demonstrated normalization of previously markedly abnormal jitter that paralleled marked improvement in clinical outcome measures.

 

Thymoma and Thymectomy in SNMG

“Diagnosis of myasthenia gravis” Bird, S, UpToDate, August 2022

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. (See "Role of thymectomy in patients with myasthenia gravis".)

 

Novel Treatment for SNMG

“Eculizumab in the Treatment of Seronegative Refractory Generalized Myasthenia Gravis.” Singh et al., Neurology, April 2020, Volume 94, (15 Supplement) 1691.

This small analysis provided preliminary evidence for the efficacy of Eculizumab in the treatment of refractory generalized MG.

 

 

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