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Learn More About MG

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Autoimmune Myasthenia Gravis

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What Causes Autoimmune MG?

The voluntary muscles of the entire body are controlled by nerve impulses that arise in the brain. These nerve impulses travel down the nerves to the place where the nerves meet the muscle fibers. Nerve fibers do not actually connect with muscle fibers. There is a space between the nerve ending and muscle fiber; this space is called the neuromuscular junction.

When the nerve impulse originating in the brain arrives at the nerve ending, it releases a chemical called acetylcholine. Acetylcholine travels across the space to the muscle fiber side of the neuromuscular junction where it attaches to many receptor sites. The muscle contracts when enough of the receptor sites have been activated by the acetylcholine. In MG, there is as much as an 80% reduction in the number of these receptor sites available. The reduction in the number of receptor sites is caused by antibodies that destroy or block the receptor site.

Antibodies are proteins that play an important role in the immune system. They are normally directed at foreign proteins called antigens that attack the body. Such foreign proteins include bacteria and viruses.

Antibodies help the body to protect itself from these foreign proteins. For reasons not well understood, the immune system of the person with MG makes antibodies against the receptor sites of the neuromuscular junction. Abnormal antibodies can be measured in the blood of many people with MG. There are currently three commercially available tests for the abnormal antibodies, the AChR (acetylcholine eceptor), MuSK (muscle specific kinase) and low density lipoprotein related protein 4 (LRP4) antibodies. These antibodies destroy the receptor sites or make them unavailable. Muscle weakness occurs when acetylcholine cannot activate enough receptor sites at the neuromuscular junction.

 

Clinical Features and Symptoms

MG occurs in all races, both genders and at any age. MG is not directly inherited nor is it contagious. It does occasionally occur in more than one member of the same family. MG may affect any muscle that is under voluntary control. Certain muscles are more frequently involved, and these include the ones that control eye movements, eyelids, chewing, swallowing, coughing and facial expression. Muscles that control breathing and movements of the arms and legs may also be affected. Weakness of the muscles needed for breathing may cause shortness of breath, difficulty taking a deep breath and coughing.

 

The muscle weakness of MG increases with continued or repetitive activity and improves after periods of rest. The muscles involved may vary greatly from one person to the next. In some people, weakness may be limited to the muscles controlling eye movements and the eyelids. This form of myasthenia is referred to as ocular MG. Generalized MG refers to those people with MG who have weakness involving muscles outside the eye region. In the most severe form of generalized MG, many of the voluntary muscles of the body are involved, including those needed for breathing. The degree and distribution of muscle weakness for many people falls in between these two extremes. When the weakness is severe and involves breathing, hospitalization is usually necessary.

 

Diagnosis

There are many disorders that cause weakness. In addition to a complete medical and neurological evaluation, a number of tests may be used to establish a diagnosis of MG. Blood tests for the abnormal antibodies can be performed to see if they are present. Electromyography (EMG) studies can provide support for the diagnosis of MG when characteristic patterns are present. The edrophonium chloride (Tensilon®) test is performed by injecting this chemical into a vein. Improvement of strength immediately after the injection provides strong support for the diagnosis of MG. Sometimes all of these tests are negative or equivocal in someone whose story and examination still seem to point to a diagnosis of MG. The positive clinical findings should probably take precedence over negative confirmatory tests.

 

Treatment

There is no known cure for MG, but there are effective treatments that allow many—but not all—people with MG to lead full lives. Common treatments include medications, thymectomy, plasmapheresis (also called total plasma exchange and abbreviated as PLEX or TPE) and intravenous immunoglobulins (IVIg). Spontaneous improvement and even remission may occur without specific therapy.

 

Medications are most frequently used in treatment. Anticholinesterase agents (e.g., Mestinon®) allow acetylcholine to remain at the neuromuscular junction longer than usual so that more receptor sites can be activated. Corticosteroids (e.g., prednisone) and immunosuppressant agents (e.g., Imuran®, CellCept®) may be used to suppress the abnormal action of the immune system that occurs in MG. Intravenous immunoglobulins (IVIg) are also sometimes used to affect the function or production of abnormal antibodies.  Recently, monoclonal antibodies have been investigated for use in MG.   Rituximab has been found to be an effective treatment for MuSK positive patients, and is currently being tried for those positive for AChR.  In 2016, a new treatment for MG called Soliris (eculizimab) was approved to treat people with MG who are AChR positive and have not responded well to other therapies. 

 

Thymectomy (surgical removal of the thymus gland) is another treatment used in some people with MG. The thymus gland lies behind the breastbone and is an important part of the immune system. When there is a tumor of the thymus gland (present in 10-15% of patients diagnosed with MG), it is nearly always removed because of the risk of malignancy. Thymectomy frequently lessens the severity of the MG weakness after some months. In some people, the weakness may completely disappear. The degree to which the thymectomy helps varies with each person.

 

Plasmapheresis, or plasma exchange (PLEX), may also be useful in the treatment of MG. This procedure removes the abnormal antibodies from the plasma portion of the blood. The improvement in muscle strength may be striking, but is usually short-lived, since production of the abnormal antibodies continues. When plasmapheresis is used, it may require repeated exchanges. Plasma exchange may be especially useful during severe MG weakness or prior to surgery.

 

Treatment decisions are based on knowledge of the natural history of MG in each patient and the predicted response to a specific form of therapy. Treatment goals are individualized according to the severity of the MG weakness, the person’s age and sex, and the degree of impairment.

 

Prognosis

The current treatments for MG are sufficiently effective that the outlook for most people with MG is bright.  However, some patients do not find current treatments to be effective and these people may face severe difficulties in managing even basic “activities of daily living” such as brushing one’s hair to name just one such activity.     

 

Although current treatments will not cure MG, and there is no treatment that is universally effective or tolerated by all people with MG, most  people with MG can expect to have significant improvement in their muscle weakness.  In some cases, MG may go into remission for a time, during which no treatment is necessary. There is much that can be done, but still much to be understood. New drugs with greater efficacy and fewer side effects are needed. Research plays an important role in finding new answers and treatments for MG-and the future of MG research has never been brighter.

Azathioprine

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What is azathioprine?

Azathioprine is an immunosuppressive medication that decreases the actions of the body’s immune system. Drugs that suppress the immune system are used in people with myasthenia gravis (MG) because MG is an autoimmune disorder that results from production of abnormal antibodies.  Azathioprine has been used as a treatment for MG since 1967. Azathioprine is available in a generic formulation or as the brand name Imuran®.

 

How does azathioprine work?

Under normal circumstances, the immune system produces antibodies that protect your body against infection from invading bacteria and viruses.  In autoimmune MG, the immune system produces several antibodies, the most common class of antibodies target the acetylcholine receptor (AChR).  These are called: AChR-antibodies.” The AChR-antibodies block neuromuscular transmission and lead to muscle weakness. Azathioprine suppresses the immune system and reduces the production of antibodies.  This allows the neuromuscular transmission to function normally, resulting in a return of muscle strength.


The efficacy of azathioprine is not immediately apparent—and your doctor may ask you to be patient and stick with the protocol even though you are not seeing results right away.  It may take 3-12 months to know if the drug is working for you.  If it is, you will see gradual improvement in muscle strength and decrease in severity of symptoms.  This improvement may decrease the need for other MG treatments, most particularly as the corticosteroid class of medications, including prednisone. The maximum clinical improvement may occur during the first two years of therapy.  

 

What are some special considerations when taking azathioprine?

In using azathioprine, your doctor and you must consider its risks and benefits. Your doctor will want to perform a physical examination and gather a complete medical history and learn about any chronic or serious medical conditions and any medications that  you have been taking, especially allopurinol  (Zyloprim®), ACE inhibitors  such as Lotensin",  Zestril® or Altace", and the blood thinner Coumadin®.  Other medications may interact with azathioprine and you should always discuss any prescription or over the counter drugs used with your physician and pharmacist. The normal metabolism of azathioprine requires the presence of an enzyme thiopurine methyltransferase (TPMT).  A portion of the population has reduced or absent TPMT activity and therefore do not process azathioprine properly. Prior to the initiation of azathioprine activity, a blood test for TMPT activities should be performed to avoid toxicity.  

Before taking azathioprine, you should tell the doctor if you have had an unusual or allergic reaction to this medicine previously.  The doctor will want to know if you have any disease of the liver or pancreas.  Azathioprine may cause skin rashes, fever and flu-like symptoms and it is imperative for you to notify your doctor when such symptoms occur. Azathioprine may cause bone marrow suppression (resulting in anemia/low white blood cell and platelet counts) and liver damage (elevation of liver enzymes).  Therefore, your doctor will check blood tests regularly to monitor for significant changes. In general, blood tests are done more frequently at the beginning of azathioprine therapy and gradually become less frequent. Ask your physician to discuss other possible, infrequent or theoretical complications, such as certain types of malignancies.

 

How should azathioprine be taken?

It is important to take azathioprine exactly as directed by your doctor.  Never increase, decrease or stop taking azathioprine without checking with the physician. Patients with MG may have to stay on this medication indefinitely-- it is a long-term treatment.
 

The dosage of azathioprine is weight-based and varies from IOO mg. to 300 mg. per day.  If you miss a dose while on a once daily schedule, skip the dose that was missed and return to the regular schedule with the next dose. Do not take a double dose. If you miss a dose while on a several times a day dosing schedule, take the missed dose as soon as it is remembered. If it is time for the next dose, take both doses together, and then resume the normal schedule.  If more than one dose is missed, check with your prescribing physician for instructions.

To prevent or lessen stomach upset, try eating small meals frequently throughout the day and avoid fried or fatty foods. Dry foods such as toast or crackers may help.  Store azathioprine at room temperature away from heat, direct light or moisture.
 

While taking azathioprine, check with your prescribing physician about any immunizations and take precautions such as frequent hand washing and avoiding close contact with others with infectious diseases as you may be more vulnerable to contracting an infection.  If you become ill with fever, chills or infection, contact your physician immediately. Always tell your physicians or dentist that you are taking azathioprine prior to having surgery or dental procedures.

 

What are the possible adverse effects of taking azathioprine?

Azathioprine is generally tolerated very well without serious adverse effects.  Most side effects may go away as your body adjusts to the medication. However, some possible adverse effects are very serious and need prompt attention. 


Stop taking azathioprine and contact your doctor immediately if any of the following occurs: hives; swelling of face, lips, or tongue; or difficulty breathing; severe nausea and vomiting, diarrhea, fever or chills, loss of appetite, abdominal pain, skin rash (especially chicken pox or shingles), cough, cold sores in the mouth or on the lips, sore throat, blood in the urine or stool, unusual bruising, pale stools or darkened urine, yellowing of skin and eyes, darkening of the skin and fingernails, muscle or joint pain, hair loss, fatigue or a missed menstrual period.
 

Cautionary Drugs

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Cautionary Drugs

Certain medications and over the counter preparations may cause worsening of MG symptoms. Remember to tell any doctor or dentist about your MG diagnosis. It is important to check with your doctor before starting any new medication including over the counter medications or preparations.

 

Drugs to avoid or use with caution in MG*

Many different drugs have been associated with worsening myasthenia gravis (MG). However, these drug associations do not necessarily mean that a patient with MG should not be prescribed these medications. In many instances, reports of worsening MG are very rare.  In some instances, there may only be a “chance” association (i.e. not causal). 
In addition, some of these drugs may be necessary for a patient’s treatment and should not be deemed “off limits”. It is advisable that patients and physicians recognize and discuss the possibility that a particular drug might worsen the patient’s MG. They should also consider, when appropriate, the pros and cons of an alternate treatment, if available. 
It is important that the patient notify his or her physicians if the symptoms of MG worsen after starting any new medication. Only the more common prescription drugs with the strongest evidence suggesting an association with worsening MG are provided in the list below. 

  • Telithromycin: antibiotic for community acquired pneumonia. The US FDA has designated a “black box” warning for this drug in MG. Should not be used in MG. 
  • Fluoroquinolones (e.g., ciprofloxacin, moxifloxacin and levofloxacin): commonly prescribed broadspectrum antibiotics that are associated with worsening MG. The US FDA has designated a “black box” warning for these agents in MG. Use cautiously, if at all. 
  • Botulinum toxin: avoid. 
  • D-penicillamine: used for Wilson disease and rarely for rheumatoid arthritis. Strongly associated with causing MG. Avoid 
  • Quinine: occasionally used for leg cramps. Use prohibited except in malaria in US. 
  • Magnesium: potentially dangerous if given intravenously, i.e. for eclampsia during late pregnancy or for hypomagnesemia. Use only if absolutely necessary and observe for worsening. 
  • Macrolide antibiotics (e.g., erythromycin, azithromycin, clarithromycin): commonly prescribed antibiotics for gram-positive bacterial infections. May worsen MG. Use cautiously, if at all. 
  • Aminoglycoside antibiotics (e.g., gentamycin, neomycin, tobramycin):used for gram-negative bacterial infections.  May worsen MG. Use cautiously if no alternative treatment available. 
  • Corticosteroids: A standard treatment for MG, but may cause transient worsening within the first two weeks. Monitor carefully for this possibility (see Table 1). 
  • Procainamide:  used for irregular heart rhythm. May worsen MG. Use with caution. 
  • Desferrioxamine: Chelating agent used for hemochromatosis. May worsen MG. 
  • Beta-blockers: commonly prescribed for hypertension, heart disease and migraine but potentially dangerous in MG. May worsen MG. Use cautiously.
  • Statins (e.g., atorvastatin, pravastatin, rosuvastatin, simvastatin): used to reduce serum cholesterol. May worsen or precipitate MG.  Use cautiously if indicated and at lowest dose needed.   
  • Iodinated radiologic contrast agents: older reports document increased MG weakness, but modern contrast agents appear safer.  Use cautiously and observe for worsening. 

 

Addendum from MGFA’s Medical and Scientific Advisory Board:

Checkpoint inhibitors: Immunotherapy for cancer is an exciting treatment advance for many types of cancers. However, one newly recognized rare side effect of some of these treatments is myasthenia gravis (MG). MG is recognized as a rare complication of immune checkpoint inhibitors (ICIs) for cancer (immunotherapy). People who did not have MG before beginning immunotherapy have a higher likelihood of developing the disease , although worsening of myasthenic weakness has been reported in people with existing, previously-diagnosed MG. The average onset of MG symptoms is within 6 weeks (range 2–12 weeks) of starting immunotherapy. To date, development or exacerbation of MG has been reported for pembrolizumab, although it has also been seen with nivolumab, ipilimumab and other ICIs. Risk may increase with administration of combinations of ICIs. Patients with MG and cancer considering cancer immunotherapy should talk to their oncologist and neurologist about this possible side effect. Likewise, doctors evaluating new-onset weakness in cancer patients on immunotherapy should consider MG. Additionally, MG with ICIs can be accompanied by inflammation of skeletal and/or heart muscle. MG patients who experience worsening weakness following ICI treatment should contact their neurologist and oncologist immediately.

Examples of immune checkpoint inhibitors (ICIs):

  • Pembrolizumab (Keytruda)
  • Nivolumab (Opdivo)
  • Atezolizumab (Tecentriq)
  • Avelumab (Bavencio)
  • Durvalumab (Imfinzi)
  • Ipilimumab (Yervoy)

Dental Treatment Considerations

Patients with MG may require special management considerations. These include modifying dental treatment to accommodate altered muscle strength, identifying and managing myasthenic weakness or crisis, avoiding the potential of harmful drug interactions, and monitoring oral side effects of drugs and therapies used to treat MG.

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Appointment Scheduling

Oral infections and/or stress of anticipating or undergoing dental treatment may precipitate or worsen myasthenic symptoms. Short-duration morning appointments may minimize fatigue and take advantage of the typically greater muscle strength experienced by most people with MG during the morning hours. Appointments are best scheduled approximately one to two hours following oral anticholinesterase (Mestinon) medication so as to benefit from maximum therapeutic effects and decrease the risk of myasthenic weakness or crisis.

 

Private Office or Hospital

A stable MG patient with limited or mild neuromuscular involvement you may be safely treated in the private dental office setting in most instances. However, if the patient suffers from frequent or significant exacerbations of the pharyngeal and/or respiratory tracts or from generalized weakness, he or she is most safely treated in a hospital dental clinic or other facility with emergency intubation and respiratory support capabilities.

 

Dentures

A patient’s ability to manage complete dentures may be compromised by the inability of the weak muscles to assist in retaining the lower denture and to maintain a peripheral seal for the upper denture. Over extended and over contoured maxillary dentures with thick flanges that impinge upon muscle and frenal attachments can lead to muscle fatigue and altered salivation. Improperly fitting dentures may exacerbate symptoms of difficulty in closing the mouth, tongue fatigue, a tight upper lip, dry mouth, impaired phonation, dysphagia, and masticatory problems.

 

Respiratory Collapse

If respiratory collapse occurs, an open airway and adequate respiratory exchange must be established. Dental staff should be trained in and prepared to do basic life support (CPR) until an ambulance arrives, when needed. Dental suction devices can be used to suction secretions and debris from the oropharynx to prevent aspiration and mechanical blockage of the airway. Manual retraction of the weakened tongue may prevent obstruction of the airway.

 

Oral Findings

  • Tongue: Atrophy of the tongue (loss of muscle, replacement with fat) may result in a furrowed and flaccid clinical appearance. In severe cases, it can result in a triple longitudinal furrowing of the tongue.
  • Mouth Drop: Lack of muscle strength in the lower jaw muscle, especially following a sustained chewing effort, may cause the mouth to hang open, unless the mandible (lower jaw) is held shut by hand.
  • Chewing/Swallowing: Lack of strength of the muscles of chewing strength can inhibit proper eating of food.  Eating can be further inhibited by dysphagia (difficulty swallowing), when the tongue and other muscles used for swallowing are involved; also by aberrant passage of food or liquids from the nasopharynx into the nasal cavity, when the palate and pharynx muscles are affected. The consequences of this may include poor nutrition, dehydration and hypokalemia (reduced potassium levels).

Drug Interactions

Many common drugs used in dentistry may have potential complications for MG patients by exacerbating their muscle weakness or interfering with breathing. The following table may be of help to the myasthenic patient and the treating dentist. Please remember that this list cannot cover all potentially dangerous medications and one should consult with their treating physician if there are any questions.
 

Eculizumab

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What is eculizumab?

Eculizumab is a medication that suppresses the immune system. Sometimes, it is prescribed for individuals with autoimmune myasthenia gravis (MG). It is manufactured as a solution for intravenous infusion under the brand name Soliris®. 

 

Why am I being treated with eculizumab?

Eculizumab is prescribed for some individuals with refractory, generalized MG associated with acetylcholine receptor antibodies (AChR). Refractory refers to people who have significant MG symptoms despite aggressive treatment with other medications that suppress the immune system. 

 

How does eculizumab work?

Eculizumab blocks one mechanism used by the immune system to destroy foreign invaders such as bacteria and viruses. In autoimmune MG, this portion of the immune system also damages the muscle endplate region and causes weakness. 

 

How soon should I see a response?

Individuals who respond to eculizumab often see improvement in the first one to two months. However, it may take up to 12 weeks for some people with MG to see improvement. Unless another MG treatment is used, or your MG goes into remission, the eculizumab infusions must be continued indefinitely to sustain the improvement. 

 

How is eculizumab given? 

Eculizumab is given as a series of intravenous infusions. The first five doses are given weekly, and subsequent doses are given every two weeks. In adults, the infusions are performed in a little more than ½ hour. 

 

What are the risks associated with eculizumab?

Eculizumab lowers the ability of the immune system to fight certain infections, especially meningococcal infections that cause life-threatening sepsis and meningitis. Patients must therefore be vaccinated against the meningococcus bacteria a minimum of two weeks before starting eculizumab. They must also receive periodic booster vaccinations to maximize their immunity to meningococcus and similar bacteria. The available meningococcal vaccines help protect against infections involving many, but not all types of meningococcal bacteria. It is important to realize that vaccinations reduce but do not eliminate the possibility of meningococcal infection, especially in patients taking other immunosuppressive medications. 

 

When should I seek medical care for possible meningococcal infection? 

Call your doctor or seek emergency medical care immediately for signs and symptoms of a meningococcal infection including:

  • Headache with nausea or vomiting
  • Headache and a fever
  • Headache with a stiff neck or stiff back 
  • Fever
  • Fever and a rash
  • Confusion
  • Muscle aches with flu-like symptoms
  • Eyes sensitive to light

What are other concerns associated with eculizumab?

Eculizumab is expensive, which can present a major issue in accessing the treatment. It is important to discuss the cost of this medication with your health insurance provider and infusion provider to prevent financial difficulties. 

Because of the risks related to eculizumab, prescribing physicians must be enrolled in the Soliris® Risk Evaluation and Mitigation Strategy (REMS) program in order to educate patients about the risk of meningococcal infection and to ensure that patients are properly vaccinated. 
 

Effects of MG on Voice, Speech and Swallowing

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Background

Dysphonia (voice disorder) is relatively common in the general population, occurring in about a third of all people at some point in their lifetime but occurs in only about 2% of persons with MG. On the other hand, dysarthria (slurred speech) is less common in the general population, but occurs in over 10% of people with myasthenia gravis. Difficulty voicing or speaking can affect job performance and may cause a person to feel socially isolated because they have a hard time being heard or understood.
 

Human voice production starts by generating air pressure in the lungs. It flows through the vocal folds (vocal cords), causing them to vibrate and produce sound. Symmetric and fluid vibration of the vocal folds creates a pleasing, smooth voice. Human speech is produced by using the muscles of the throat, jaw, palate, tongue, and lips to shape the sound generated by the voice box into consonants and vowels. When the muscles of the lungs, vocal tract, throat or mouth are affected in MG, we may see symptoms of voice, speech, and swallowing problems.
 

Voice problems seen in MG include vocal fatigue (voice wears out over the day or with prolonged speaking tasks), difficulty controlling pitch, or a monotone voice (lack of ability to change vocal pitch). The voice problem can stem from poor breath support or from weakness causing the vocal folds not to move properly. Speech disturbances include a hypernasal voice or slurred speech (dysarthria). Dysarthria is more frequently seen in younger patients diagnosed with MG, whereas dysphonia is more often seen in elderly men with MG. Typically, the symptoms appear and/or worsen with continuing or extended speech.

 

Diagnosis

The diagnosis of dysphonia or dysarthria is often very apparent to a person with MG because they perceive a change in their voice or speech production. Sometimes, the symptoms may be subtle or intermittent. A speech-language pathologist or a medical doctor makes the diagnosis. Since dysarthria is a common symptom of stroke, any new onset of dysarthria should be immediately evaluated by a medical professional. Any person with vocal disturbance lasting more than 2 weeks should seek medical attention in a timely manner.
 

If you are experiencing a voice disorder, you may be referred to an ear, nose, and throat (ENT) physician to be sure that the dysphonia is due to MG and not another cause. The ENT physician will usually perform a laryngoscopy. This is a relatively straightforward examination that uses a small flexible camera inserted through the nose to visualize the upper airway. It is done with local anesthesia in the office setting and only takes a few minutes to complete.

 

Treatment

The treatment of speech and voice disorders in MG is individualized and based on the underlying cause and severity of the problem. Pharmacological therapies used for other symptoms of MG are typically utilized. Other treatments may involve therapy with a speech-language pathologist. Strengthening exercises and/or compensatory strategies may be employed to help increase understandability. A strengthening program is not indicated during a myasthenic crisis or exacerbation, but may be implemented during stability or when in remission. Exercises should be performed during peak drug therapy. Always review any plan of care with your MG treating provider.
 

Improvement and prognosis of voice and speech is often related to the treatment of overall MG disease. Research will continue to play an important role in answering questions and developing new tr

Emergency Alert Card

Download and complete the Emergency Alert Card in the event of an MG Crisis

I have myasthenia gravis (MG), a disease that can make me so weak that I may have difficulty standing or speaking clearly. In addition, I may have drooping eyelids, double vision, and even difficulty breathing or swallowing. Sometimes these symptoms are mistaken for intoxication. If my breathing and swallowing difficulty is severe, I may be having an “MG crisis” or “MG exacerbation” that warrants emergency treatment.

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Emergency Management for First Responders

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Triggers which may worsen MG muscle weakness include:

  • Medications

    • High doses of steroids

    • IV magnesium

    • Some antibiotics

    • Certain heart/blood pressure medications

    • Some general anesthetics and paralytics

    • Botulinum toxin

    • Stopping or reducing medications used to treat MG

  • Illness or infection

  • Heat

  • Stress from trauma or surgery

Myasthenic Crisis

  • A potentially life-threatening complication of myasthenia gravis. Respiratory failure occurs due to weakness of respiratory muscles and mechanical ventilation is required.  

  • Repiratory failure may also develop due to weakness of muscle that keep the airway open.  BiPAP may be sufficient or the patient may need endotracheal intubation.

  • Careful assessment and monitoring is required as myasthenic crisis presents differently from other forms of respiratory failure. 

  • Prompt recognition of impending myasthenic crisis may prevent fulminant crisis from developing.

PRE-HOSPITAL RESPIRATORY ASSESSMENT AND MANAGEMENT
Check for tachypnea:

  • Rapid shallow breathing is seen in MG patients to compensate for weak respiratory muscles.

  • Pulse oximetry is NOT a good indicator of respiratory strength in MG patients as abnormalities often develop only after life-threatening respiratory failure has already occurred. This is distinct from other causes of respiratory failure. Careful observation of respiration and bedside measurements (forced vital capacity, single breath count) are more reliable indicators of respiratory status than pulse oximetry in MG patients. 

Inspect for use of accessory muscles of respiration:

  • Check for retraction of supraclavicular fossa and intercostal spaces as indicators of respiratory accessory muscle usage. Patients may also use neck and abdominal muscles. Use of accessory respiratory muscle in MG patients is an important sign that respiratory effort may not be sustained. However, generalized muscle weakness in MG patients can at times mask accessory muscle usage.

  • Paradoxical breathing and inability to lie supine or speak more than a few words are indicators of diaphragm weakness.

  • Weak neck flexion also correlates with diaphragmatic dysfunction. Neck flexion strength can be tested by having the patient lie supine and attempt to lift his/her head off the stretcher and tuck his/her chin. 

  • Severe slurred speech and difficulty managing secretions are also signs of potential impending MG crisis

Single breath count test:

  • Single breath count test is a good bedside measurement of respiratory function which can be performed quickly and without additional equipment

  • To perform, ask patient to count out loud after maximal inspiration. Ability to reach 50 indicates normal respiratory function. Single breath count of less than 15 typically correlates with low forced vital capacity (FVC) and respiratory muscle weakness. 

Immediate management:

  • Elevate head of the stretcher, keep patient cool and have suction available
  • Oxygen usage is helpful but does not alleviate respiratory distress in MG patients. Titrate to keep oxygen saturation at 94-98% on pulse oximetry. If breathing is inadequate, provide assistance with ventilation immediately. Non-invasive ventilation may be given via bag-valve mask (BVM) or BiPAP.
  • Invasive ventilation is needed when airway patency cannot be maintained or when noninvasive ventilation is unsuccessful.
  • Transport patient immediately. Alert ED to the patient’s history of MG. Bring medical history paperwork if patient has it readily available
     

In-Hospital Initial Assessment and Management

Measure forced vital capacity (FVC) and negative inspiratory force (NIF) at baseline and trend, typically every 6 hours or more or less frequently, as needed. Trend of numbers over time is more important than individual test results. A declining NIF or NIF worse than 20 cm H2O and FVC less than 10 to 15 mL/kg typically prompts BiPAP or intubation.  However, abnormal PFTs are always interpreted in the context of the patient’s clinical picture. BiPAP may be indicated earlier for FVC less than 20 ml/kg or NIF worse than 30 cm H2O if patient is able to clear his/her secretions and has adequate bulbar strength.

Careful observation (tachypnea and use of accessory muscles) and bedside measurements (forced vital capacity, single breath count) are much more informative than pulse oximetry or ABG results. Measuring FVC upright and supine can sometimes provide insight, as decline in the supine position may indicate neuromuscular weakness. 

  • Pulse oximetry and arterial blood gas (ABG) measurements are NOT good indicators of respiratory strength in MG patients as abnormalities often develop only after potentially life-threatening respiratory failure has already occurred.

  • Do not wait for ABGs to show hypoxemia or hypercapnia.

  • These are late developing signs that appear only immediately prior to respiratory arrest in MG patients. Weak respiratory muscles may suddenly fatigue, producing precipitous respiratory collapse.

BiPAP is an alternative to intubation in MG patients without hypercapnia who are able to clear secretions. Patients may have their own BiPAP or NIV equipment.  Depending on local guidelines, patients may be able to use this if it remains medically appropriate for the presenting clinical scenario.

 

Next Steps

MG patients with impending or actual MG crisis should be admitted to an intensive care unit. Signs of impending crisis with need for ICU admission include: FVC less than 2 ml/kg, NIF less than 30, serial reductions in these numbers, significant bulbar dysfunction, orthopnea and/or rapid shallow breathing.

  • Consult neurology for specific treatment options (e.g. plasma exchange, IVIG, corticosteroids etc). Consult with neurology regarding continuation of pyridostigmine if patient is intubated. Due to possibility of increased secretions, continued use may predispose patient to aspiration and ventilator associated pneumonia and is typically avoided.
  • Contact the patient’s outpatient neurologist for input regarding care of worsening myasthenia.
  • Review medication list and minimize medications which can worsen MG
  • Identify and address triggers that may have exacerbated myasthenia (see above).

Emergency Management for People with MG and Caregivers

Information and Guidance for People with MG, Families and Caregivers

  • MG Crisis vs. MG Flare
  • How to tell if an MG Crisis is developing
  • Respiratory assessment tools for people with MG
  • Emergency Assistance and Care

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Intravenous Immunoglobulin (IVIg)

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What is IVIg and how is it used?

“IVIg” is the commonly used acronym for “intravenous immune globulin.” It is also known as pooled human gamma globulin or simply gamma globulin. IVIg has been used for decades in modern medicine in the treatment of a variety of infectious or inflammatory diseases. In patients who are lacking in the antibodies necessary to fight infection IVIg replaces those lost antibodies.
 

Since 1984 IVIg has been used extensively in the treatment of various autoimmune neurological disorders including myasthenia gravis. Studies have shown that IVIg is an effective treatment for many patients with autoimmune myasthenia gravis.

 

How does IVIg work?

IVIg seems to affect the function or the production of antibodies in the immune system. The exact mechanism of how IVIg works in successfully treating myasthenia gravis and other autoimmune disorders is not entirely understood.

 

Since IVIg is a blood product, is it safe?

IVIg is felt to be very safe with regard to exposure to infection or viruses. Donors are screened for certain infections before being allowed to give blood for IVIG. The processing of IVIg inactivates infections such as HIV, Hepatitis B and C. Nonetheless, it is a human blood product that comes from multiple donors.

 

Why has IVIg been prescribed for me?

You may be prescribed IVIg for several reasons.  For many people, IVIg is used short term.  The most common usage is to treat an exacerbation where a patient has worsening symptoms despite other treatments.  IVIg is used to treat patients who are in crisis, or showing signs of impending crisis. IVIg may also be prescribed to bring a person to optimal strength prior to surgery.  Patients with MG who are treated with IVIg can be stabilized, allowing time for other treatments to begin working.  When other therapies are not effective in managing symptoms, a doctor may prescribe IVIg as maintenance therapy.
 

Since IVIg is a blood product, is it safe?

IVIg is felt to be very safe with regard to exposure to infection or viruses. Donors are screened for certain infections before being allowed to give blood for IVIG. The processing of IVIg inactivates infections such as HIV, Hepatitis B and C. Nonetheless, it is a human blood product that comes from multiple donors.

 

Are there adverse effects that occur with IVIg treatments?

Most people with MG tolerate IVIg, well.  . However, there are several adverse effects that may occur. .  You may develop a headache, chills and aches during the infusion. Slowing the infusion rate and using medicines to relieve these symptoms is often helpful.|
 

You may also experience fatigue, fever or nausea that may persist up to 24 hours after the infusion. Other side effects may include a headache, rash or a more severe allergic type reaction. Since IVIg is a highly concentrated protein it may interfere with blood flow and clotting and rarely renal function.  

 

How is treatment with immunoglobulin administered?

IVIg treatments are administered intravenously. The medication is infused slowly over a number of hours. The dose is based on your weight. You might be treated with a series of infusions over a period of three to five days that is repeated at an interval determined by your doctor. For some patients the infusion is given in a physician’s office, while others may have it in the home using a home health agency. If you have been severely weakened, or are showing symptoms of impending crisis, you are likely to be treated in the hospital. A week or two may be required before you feel the onset of improvement, although this varies from patient to patient. The duration of improvement from IVIg varies but typically is a few weeks to a few months.

 

What are other concerns about using IVIg?

IVIg is expensive and so is not often prescribed as first line maintenance therapy.  . It is important to discuss the cost issues with your health insurance provider and infusion provider to prevent financial difficulties.

MG Patient Registry

Do you want to wake up to a World without MG? Yes? Join the MG Patient Registry.

Why a patient registry? The MGFA launched the MG Patient Registry to help expand our knowledge about MG and move us closer to improved treatments and a cure. Through the Registry the MG Community will help identify how each of us was diagnosed, how we are being treated, our insurance challenges, and how we are feeling.

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Mycophenolate Mofetil (CellCept)

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What is mycophenolate mofetil (CellCept®)? 

Mycophenolate mofetil is an immunosuppressive medication that reduces the activity of the body’s immune system. Medications that suppress the immune system are used in patients with myasthenia gravis (MG) because MG is an autoimmune disorder that results in production of abnormal antibodies directed against a patient’s own muscle tissue instead of a foreign entity (e.g. bacteria). Originally approved  as a transplant anti-rejection drug, mycophenolate mofetil has been found to be helpful in autoimmune illnesses like MG.

 

How does mycophenolate mofetil work? 

Under normal circumstances, the immune system produces proteins called antibodies that protect the body from infections (e.g. viruses and bacteria) and from abnormally growing cells (e.g. cancers). In autoimmune MG, the immune system becomes confused and produces abnormal antibodies directed against a patient’s own muscle tissue. The abnormal antibodies block or destroy important receptors on the muscle resulting in muscle weakness. 

Mycophenolate mofetil reduces the production of lymphocytes, the white blood cells that produce antibodies. Reduction of the abnormal antibodies in MG allows muscle tissue to heal and function more normally. As muscle heals, patients experience an improvement in muscle strength.

 

How is mycophenolate mofetil used in the treatment of MG?

Mycophenolate mofetil may be used together with another immunosuppressant agent such as prednisone, or as the only immunosuppressive agent. In many MG patients, medications like mycophenolate mofetil are used to reduce the dose of corticosteroids (e.g. prednisone) or eliminate the need for corticosteroid therapy completely. It may take you 6 – 14 months to notice improvement from mycophenolate mofetil therapy. When mycophenolate mofetil treatment is successful, you should notice gradual improvement in muscle strength and reduced need for other MG medications during this time period. Once  you have been  on mycophenolate mofetil for  an extended period (3 – 5 years) of stability with good muscle strength, you and your physician can discuss slowly reducing the dose.


What are some special considerations to discuss with your health care provider before starting mycophenolate mofetil? 

Before prescribing mycophenolate mofetil, your MG physician will ask you if you have anemia or any blood conditions, unusual bleeding or bruising, or any viral or bacterial infections. 

If you are a woman, your physician will want to know if you are pregnant, planning on getting pregnant, or breast feeding.  First trimester pregnancy loss and congenital malformations have been reported with patients taking mycophenolate mofetil. Women who are planning a pregnancy or who become pregnant while taking mycophenolate mofetil should discuss potential risks and options with their physician. It is recommended that women of child bearing age use two forms of birth control simultaneously when treated with mycophenolate mofetil.

 

How should mycophenolate mofetil be taken? 

Mycophenolate mofetil is an oral medication prescribed based on your body weight. Y  Take mycophenolate mofetil exactly as prescribed by your MG physician. Swallow the tablet or capsule with water. Do not crush the tablet or open the capsule. If your skin comes in contact with the contents of the capsule or a broken tablet, rinse thoroughly with water. Be certain to take this medication exactly as prescribed at regular intervals. If you miss a dose of mycophenolate mofetil, take it as soon as you can. If it is almost time for the next dose, take only that dose. Never take extra medicine or double doses. A liquid version of mycophenolate mofetil is available if you cannot swallow the capsules or tablets.

 

Does mycophenolate mofetil interact with other medicines or vaccines? 

Mycophenolate mofetil can interact with other drugs. For this reason, it is important to tell your physician about all other medicines that you are taking. Be certain to mention all over-the-counter drugs, nutritional supplements or any herbal products that you are using. Antacids, vaccines, cholestyramine (a cholesterol reducing drug) and drugs that suppress your immune system can interact with mycophenolate mofetil. 

Administration of live vaccines is not recommended in patients treated with mycophenolate mofetil. Non-live vaccines (e.g. injectable influenza vaccine) may be administered in patients treated with mycophenolate mofetil.


What are the possible adverse effects of mycophenolate mofetil? 

Your physician will carefully monitor your situation for potential adverse effects. People with MG take much smaller doses of mycophenolate mofetil than those using it to avoid transplant rejection. For this reason, common adverse effects are limited and mainly related to gastrointestinal problems including nausea and diarrhea, low white blood counts, anemia and skin rash. 

Mycophenolate mofetil and other immunosuppressant agents may increase the risk of infections. The risk of infection is higher when and if you  are treated with multiple simultaneous immunosuppressant medications. It is important to avoid individuals with infectious illnesses and to notify your physician if you develop persistent signs of infection. There is a minimally increased risk of cancer associated with mycophenolate mofetil usage. 

 

How will a physician monitor a patient taking mycophenolate mofetil? 

Appointments will be scheduled at regular intervals to monitor your progress. At these appointments, your physician will ask you a series of questions as well as perform physical examinations and laboratory tests that provide important information to evaluate the safety and effectiveness of mycophenolate mofetil in your case. To watch for anemia or a decrease in the white cell count, blood samples will typically be examined frequently during the first few months of this therapy and then less often.
 

Ocular MG

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What is ocular myasthenia gravis?

Ocular myasthenia gravis is a form of myasthenia gravis (MG) in which the muscles that move the eyes and con­trol the eyelids are easily fatigued and weakened.

 

What are the common symptoms of ocular myasthenia gravis?

People with ocular MG have trouble with sight due to double vision and/or drooping eyelids. Their eyes do not move together in balanced alignment, causing them to see “double” images. One or both eyelids may droop to cover all or part of the pupil of the eye, blocking vision.

 

These symptoms may be mild to severe. Eye weakness often changes from day to day and over the course of a day. Eye problems often worsen at the end of the day or after a pro­longed period of use. If you have ocular MG, you may find that eye problems temporarily improve after several minutes of rest.

 

People with ocular MG do not have difficulty swallow­ing, speaking or breathing, nor do they have weakness of the arms or legs. Descriptions of the symptoms that people with ocular MG may have include:

  • Double vision – Seeing two images rather than one. This results from weak­ness of the muscles that move the eyes together in alignment. The medical term for double vision is diplopia. If you have diplopia, you may experience blurred vision rather than double vision.
  • Drooping eyelids – The eyes do not appear to be opened fully. If the eyelid covers the pupil of the eye, then the vision of that eye will be obstructed. The medical term for drooping eyelids is ptosis (pronounced “toe-sis”).

 

Who gets ocular myasthenia gravis?

Problems with double vision and drooping eyelids are often the first symptoms of MG. Although most people have eye problems at the onset of MG, they may have other muscle weakness or develop other muscle weakness in the first two years after MG symptoms begin. About 15% of people with MG will have only ocular problems (ocular MG). If weakness of other muscles develops over time, the MG changes from ocular MG to generalized MG. About half of all people with ocular issues related to MG in the first year will develop generalized MG. People that have had only ocular MG symptoms for five years or more will most likely not develop generalized MG.

 

People with ocular MG are slightly more likely to have seronegative MG (no measurable autoantibodies like AChR and MuSK) compared with people with generalized MG.

 

Why are the eye muscles frequently involved in myasthenia gravis?

There may be several reasons why eye muscles are more frequently involved. However, this is not completely understood.

 

One hypothesis is that people with MG may simply notice eye weakness more often than mild weakness in other muscle groups in the body. Another hypothesis is that the eye and eyelid muscles are structurally different from muscles in the trunk and limbs. For example, these parts of the body have fewer acetylcholine (AChR) receptors, which is where the defect occurs in autoimmune MG. Eye muscles contract much more rapidly than other muscles and may be more likely to fatigue.

 

Perhaps the most important difference between eye and eyelid muscles compared with other muscles of the body is that eye muscles respond differently to immune attack. The differences in the response of eye muscles to immune attack may explain why eye muscles are also targeted in other autoimmune conditions, such as auto­immune thyroid disease.

 

How is ocular myasthenia gravis treated?

It is important to talk with your physician about the best treatment regimen for you—balancing the   severity of the symptoms and impact on quality of life with the risks and benefits of treatment. People who have primarily cosmetic problems due to ptosis or diplopia may con­sider nonpharmacological treatment, such as:

  • Wearing dark glasses in bright light, which some people find helpful.
  • Using eyelid tape (a special type of tape used to hold the eyelids open without injuring the eyelids). This can be used for ptosis and may be preferable to drug therapy that alters the immune system: using agents such as glucocor­ticoids (prednisone or similar agents), azathio­prine (Imuran®), cyclosporine or mycophenolate mofetil (CellCept®).
  • Applying a patch to one eye. This permits people with double vision to see one image. If the same eye is consistently patched, vision in that eye might decrease. Therefore, it is important to alternate the patch from one eye to the other to avoid permanent vision loss.
  • Using eyelid crutches (clever devices attached to glasses to hold the eyelids open) for ptosis.
  • Using eyeglass prisms for diplopia.

The last two treatments are uncommon, older treatment methods for ocular MG.

 

When ocular symptoms are severe or disabling, treatment with immune system modulating therapy may be considered.

Agents that improve neuromuscular transmission, such as Mestinon®, may be helpful for ptosis, but are generally not very useful for diplopia.

Thymectomy is usually not considered for people with ocular MG unless the manifestations are severe or disabling.

Eyelid or eye muscle surgery is generally not recommended for people with MG

Prednisone

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What is prednisone?

Prednisone is a synthetic hormone commonly referred to as a steroid, specifically a glucocorticoid type of steroid.  Prednisone is very similar to the hormone cortisone, which is naturally produced by your own body. Prednisone is used to treat many illnesses and medical conditions. 

 

There are several types of steroids with different actions.  Glucocorticoid steroids are very different from androgenic steroids that have received publicity as “performance enhancing” drugs that have been misused by athletes.  Brand names for prednisone include Deltasone, Rayos, Sterapred, and Prednicot . 

There are other synthetic steroid medications that are sometimes used:

 

Prednisolone                   Brand Names: Delta Cortef Cotolone, Flo-Pred, Millipred, Orapred, Pediapred

Dexamethasone              Brand Names: Decadron, Ozurdex

Hydrocortisone               Brand Names: Solu-cortef, Anucort-hc, Cortaid, Cortef, Pandel, Locoid,

Triamcinolone                 Brand Names: Aristocrot, Kenacort

 

How does prednisone work?

In part, prednisone acts as an immunosuppressant. The immune system protects you against foreign bacteria and viruses. In some illnesses, the immune system becomes overactive and attacks the body. These illnesses are referred to as “autoimmune diseases.” Some autoimmune diseases, including myasthenia gravis, are caused by antibodies. Prednisone suppresses the production of antibodies. This suppression can make it slightly harder for you to fight off infection, but also reduces the over-activity of the immune system. 

 

When beginning prednisone, there is a small chance that it may cause serious increased weakness for a short period of time and your physician should be alerted if you experience worsening symptoms of myasthenia gravis.  Most physicians try to prevent this by starting prednisone at a low dose and working up to a therapeutic level.

 

What are the possible adverse effects of prednisone?

Adverse side effects do not occur in all patients and are usually related to the amount and length of time prednisone is used. Potential adverse effects will be monitored by your physician and include:

 

·Insomnia and mood changes. Euphoria or depression may occur. The cause is uncertain. It is best to take prednisone in the morning to reduce the chances of insomnia at night.

  • Increased appetite and weight gain.  People with MG cite weight gain as the most frustrating side effect of taking this medication.  Prednisone increases your appetite. Just being aware of this can help with management.    Keeping healthy, low calorie snacks available can help. 

  • Susceptibility to infections. Prednisone slightly decreases your resistance to infection. Avoid individuals with infectious illnesses if possible. Notify your physician if you develop persistent signs of an infection.

  • Fluid retention. Prednisone can cause you to retain fluid. Your physician will monitor this process. Fluid retention can be caused by sodium retention and potassium depletion through frequent urination. A salt-restricted/potassium-rich diet may help reduce fluid retention.

  • Hypertension. Prednisone may cause a rise in blood pressure. Your physician can treat this, if necessary.

  • Skin changes. Prednisone can cause a change in the condition of your skin. You may notice that your skin bruises more easily, or that wounds take longer to heal.

  • Change of physical appearance. These changes may include swelling of the face or the back of the neck or ankles; increased belly fat; acne; thinning of skin; or skin stretch-lines.

  • Osteoporosis. Prednisone can make your bones become fragile by increasing calcium loss. This usually occurs after taking prednisone for a prolonged time. It may be recommended that you take a calcium and vitamin D supplement or increase the amount of calcium-rich foods in your diet and that you have regular bone-density screenings.

  • Cataracts and worsening of glaucoma. After prolonged use of prednisone, cataracts or glaucoma may develop. This condition can be detected and monitored by periodic regular eye examinations.

  • Hyperglycemia or diabetes (elevated blood sugar). Prednisone may increase the amount of sugar (glucose) in your blood. With periodic blood work, your physician can monitor this. Alterations in hair growth. Prednisone can cause a darkening and/or increase in hair growth. This usually disappears when the dose of prednisone is decreased.

  • Stomach upset (indigestion, stomach burning or ulcer). Prednisone may cause gastrointestinal irritation. Take prednisone with meals, milk or antacids. Do not take on an empty stomach. Your physician may prescribe an acid reducing medication such as Prilosec, Prevacid, or Protonix to protect your stomach.

 

How long will the side effects last?

If adverse effects develop, they will usually persist as long as the medication is continued.  As the dose decreases, so will the adverse effects. Some adverse effects such as bone-thinning may be permanent and will not reverse after the medication is discontinued.  

 

Are there any special dietary considerations?

Adopting a high protein/ low salt/low carbohydrate diet and eating well-balanced meals can help to control weight.

 

What should I do if I miss a dose of prednisone?

  • You should try to avoid missing a dose of prednisone. If you do, follow these guidelines:
  • If you forget to take your prednisone at the usual time but remember later the same day, take the missed dose immediately.
  • If you forgot to take yesterday’s dose, skip yesterday’s dose and take your usual dose for the day.
  • If you are on an alternate day schedule and forgot yesterday’s dose, take yesterday’s dose today. Tomorrow, resume the alternate day schedule.
  • Since prednisone suppresses the natural production of steroids by your body, stopping prednisone too quickly can lead to serious, even life-threatening effects including low blood pressure, low body temperature, heart failure, confusion, and other effects.
  • Rapidly tapering or stopping prednisone can also be associated with worsening of the symptoms of myasthenia gravis, nausea, vomiting, pain, or fever.
  • Never stop or change your prednisone dose without your doctor’s consent. If you are planning a trip, always carry an extra supply.

 

How are the dosages of prednisone determined?

Schedules are determined by the body’s response to the prednisone. Severity of myasthenia gravis, control of myasthenia gravis symptoms, and the development of adverse effects are all taken into consideration when your physician determines your dosage of prednisone.  You and your physician will work together to try to reach the lowest dose possible to keep you strong enough to manage your daily activities. You may also discuss the addition of “steroid sparing” strategies, such as adding other immunosuppressants such as mycophenolate (Cellcept) or azathioprine (Imuran).  

 

What is meant by the terms “Alternate Day,” “High Day,” “Low Day” and “Off Day”?

These are terms used to describe typical dosage patterns of prednisone.

 

  • Alternate Day is when you take prednisone every other day (for example 10 mg today, take nothing tomorrow, take 10 mg the following day, etc.)

  • High Day and Low Day refer to the dosages you take on the alternate day schedule usually used when beginning to taper the drug.

    • High Day is the day when you take the higher dose of prednisone.

    • Low Day is the day when you take the lower dose of prednisone.

Example:

Sun

Mon

Tue

Wed

Thu

Fri

Sat

Sun

60

20

60

20

60

20

60

20

High

Low

High

Low

High

Low

High

Low

 

 

 

 

The above dose would be described as 60/20. 60 mg. is the dose being taken on the high day; 20 mg. is the dose taken on the low day. It may be helpful to write the dosage on a calendar to help you remember the correct dosage for the day.

•    Off Day describes a day when your prednisone dose is 0 mg (when you don’t take any prednisone).

 

Is it important for others to know that I am taking prednisone?

Yes. Any doctor or dentist who is taking care of you should know you are taking prednisone.  In case of an emergency, your family or close friends should also know you are taking prednisone.   Carry an identification card stating that you are taking prednisone and any other medications, and include your doctor’s name and phone number. This is all valuable information should an emergency occur.

Pregnancy and MG

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Myasthenia Gravis in Pregnancy

If you are a woman with myasthenia gravis (MG) and are considering  pregnancy, you will want to discuss your plans with  your MG treating provider well in advance. This will permit adequate time for you and your provider to make any adjustments to your MG treatment plan, allowing for the best outcomes with the least risks for you and your baby. You and your health care providers will also want to discuss  the safety of your current treatment plan during a pregnancy and the avoidance or discontinuation of any therapies that might have unwanted effects on the growing fetus. The impact of changes in your treatment plan on your own health is also an important consideration.

 

Treatment During Pregnancy

The treatment of MG in pregnancy is similar to treatment in non-pregnant patients. The majority of patients under good control prior to pregnancy will remain stable throughout the pregnancy. When there is worsening, it is more likely to occur in the weeks after the delivery of your baby.

Oral pyridostigmine (Mestinon®) is the standard first-line treatment during pregnancy. Intravenous anticholinesterase inhibitors (like pyridostigmine) should not be used during pregnancy as they may produce uterine contractions. However, these should be administered during labor in place of oral dosing.

Prednisone is the immunosuppressant agent of choice during pregnancy. When prednisone is insufficient or poorly tolerated, azathioprine or cyclosporine are considered relatively safe by a consensus of MG experts. However, some MG experts are  opposed to using azathioprine in pregnancy.

Either lasmapheresis (PLEX) or IVIg may be used when a prompt temporary response is needed during pregnancy.

Thymectomy should be postponed until after pregnancy.

 

Planning the Delivery

You should carefully consider where you will give birth. Whenever possible, most pregnant women want the obstetric team who has cared for them throughout the pregnancy to deliver the baby and care for them in the postpartum period. During the course of the pregnancy, the MG provider and the obstetrics team must be in communication about the treatment plans, the progress of the pregnancy, and plans for delivery.  There may be advantages to choosing an obstetric team that performs deliveries at the same medical center where you are treated for MG. Home births and deliveries at birthing centers outside of large hospital centers are typically not recommended for patients with complex medical issues.   Maternal MG presents with special considerations for the infant as well as the mother.  Babies whose mothers have MG may need special care immediately upon delivery (see “Transient Neonatal MG” below). 

 

Labor & Delivery

As a pregnant woman with MG, you can expect to have a typical labor and a spontaneous vaginal delivery. Consultation with an anesthesiologist before labor commences is advised. Regional anesthesia is recommended when vaginal delivery is expected. Magnesium sulfate, frequently used for preeclampsia and eclampsia is not recommended in patients with myasthenia as it can precipitate a myasthenic crisis.

 

Transient Neonatal MG

Infants born to mothers with autoimmune MG typically will need to be examined immediately  after birth and observed by skilled neonatal doctors and nurses for the first 3 to 4 days for any signs of transient myasthenic weakness, even if the mother’s myasthenia is well-controlled. A small number will require some very short-term support of breathing and feeding. Infants with transient neonatal myasthenia do not continue to have myasthenia once auto-antibodies passed from mother to baby through the placenta have been removed or spontaneously broken-down.

 

Reference

Sanders, DB, et al. (2016). International consensus guidance for management of myasthenia gravis: Executive Summary Neurology: 87(4), 419-425.

Pyridostigmine (Mestinon)

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What is pyridostigmine?

Pyridostigmine is a medicine used to treat the muscle weakness caused by myasthenia gravis (MG). Myasthenic weakness includes double vision, droopy eyelids, shortness of breath, trouble swallowing and arm or leg weakness.  In the United States, pyridostigmine is produced as follows:

  • 60 milligram tablet - Name Brand: Mestinon® also available in generic form

  • 60 milligram/5 milliliter raspberry-flavored syrup – Brand Name: Mestinon® Syrup

  • 180 milligram sustained release (long-acting) tan-colored tablet - Name Brand: Mestinon Timespan®.

  • Pyridostigmine injection 5 milligrams/ milliliter – Brand Name: Regonol Solution for Injection®.

 

How is pyridostigmine used in the treatment of myasthenia gravis?

There are two pill forms of pyridostigmine, regular release and the sustained release, aka Timespan.  When taken by mouth, regular release pyridostigmine works within a few minutes to improve the muscle weakness described aboveIts effects last for 3-4 hours so it must be taken repeatedly throughout the day.  The timespan form of pyridostigmine has a slower onset and longer duration of action.  Timespan can be used at bedtime to enable a person to sleep longer without need of medication.

 

How does pyridostigmine work?

When you try to move a muscle, the nerve connected to that muscle fiber at the neuromuscular junction fires an electrical impulse that causes the release of a chemical called acetylcholine (ACh) from that nerve (see Figure).  ACh travels across a small space called the synaptic cleft and binds to the ACh receptor (AChR).  The binding of ACh to the AChR triggers a local current that, if large enough, induces the muscle fiber to contract.  In autoimmune MG, AChR antibodies lead to loss of AChRs.  Too few AChRs causes the AChR current to be too small to trigger muscle contraction.  The size of the AChR current depends upon the number of AChRs and the amount of ACh in the synaptic cleft.  The loss of AChRs can be compensated by raising the concentration of ACh in the synaptic cleft.  A protein in the synaptic cleft, acetylcholine esterase AChE (see figure), breaks down ACh.  Pyridostigmine inhibits AChE, which raises the concentration of ACh in the synaptic cleft compensating for the loss of AChRs (see figure).The muscle contracts when enough of the receptor sites have been activated by the acetylcholine. Pyridostigmine allows more acetylcholine to remain at the neuromuscular junction longer than usual so that more receptor sites can be activated. More acetylcholine in the neuromuscular junction results in stronger muscle contractions and less weakness. Pyridostigmine does not cure myasthenia gravis but does help to improve the symptoms.

 

What are some important things to consider when taking pyridostigmine?

It is important for you to take pyridostigmine on time and exactly as it has been prescribed. If one dose is missed within an hour of the prescribed dose, take the missed dose and continue with the other doses as scheduled. If the dose is missed by more than one hour,   take the dose immediately and then wait the required 3 to 4 hours before taking the next dose. Take subsequent doses with the prescribed intervals as well. For example, if a dose of pyridostigmine is missed at noon and is taken at 2 p.m., the next dose would be taken at 5 or 6 p.m. or as directed by the physician. Never take a double dose to make up for a missed one.

 

What safety measures should I follow when taking pyridostigmine?

  • Watch for possible side effects and report them to your MG physician.
  • Carefully follow the prescribed dose regimen. To help your physician individualize the amount of medication you need, record the response after each dose when you first start taking pyridostigmine.
  • Recognize that choosing an optimal dose of pyridostigmine for you can be difficult because the symptoms of overdose and under dose can be somewhat similar.
  • Seek immediate medical attention if breathing and swallowing become difficult for you.
  • Refill prescriptions early, in case there is difficulty in obtaining a supply of pyridostigmine.
  • Store pyridostigmine in a dry place, never in a moist climate like the bathroom or refrigerator. Keep the original silicon drying agent stored with your medication.
  • Carry medications on your person when traveling, not in your luggage.

What are some possible adverse reactions of pyridostigmine?

  • Stomach upset, nausea, vomiting
  • Abdominal cramps and diarrhea
  • Increased salivation (can lead to choking when salivation is severe) ; drooling, and tearing
  • Increased bronchial secretions (can compromise breathing when severe)
  • Increased sweating
  • Muscle cramps
  • Muscle twitching
  • Muscle weakness
  • Headache

All adverse reactions should be reported to your MG-treating physician. Many of the adverse effects can be relieved by a change in the dose of pyridostigmine. If changing the dose does not solve the problem, the physician may add another medication to help control the adverse reactions.

 

Are all pyridostigmine or Mestinon® preparations equal?

No!

  • Regular pyridostigmine or Mestinon® comes in two forms: Mestinon® 60 mg. tablets and Mestinon Syrup® 60 mg/5 ml. The greatest effect usually occurs in 60 to 90 minutes and lasts for 3 to 4 hours.
  • Mestinon Timespan® is an extended release form of pyridostigmine bromide that slowly releases its active ingredients over an approximately 12-hour period. When prescribed, Mestinon Timespan® is usually given as a bedtime dose so that the patient does not need to wake up every 3 or 4 hours to take a dose of regular Mestinon®.
  • Mestinon Timespan® should never be substituted for regular Mestinon® or generic pyridostigmine.
  • Mestinon Timespan® should never be crushed.
  • The possible adverse effects of Mestinon Timespan® are the same as those for regular Mestinon® or generic pyridostigmine, but are possibly more likely to occur.
  • The absorption and effect of Mestinon Timespan® are sometimes erratic. Some physicians and patients prefer to schedule nighttime doses of regular Mestinon® or generic pyridostigmine.
  • Regonol Solution for Injection® 5 mg/ml. is sometimes required when patients cannot take anything by mouth. The physician will prescribe 1/30th of the usual oral dose by IM injection or very slow IV administration.
  • No single fixed dose schedule will suit all patients with MG, whose medication requirements vary from time to time, day to day, and in response to stress or infection.
  • Different muscles respond differently to a given dose of Mestinon® or generic pyridostigmine. The physician will select a dose that produces the best response in the most vitally affected muscles.

Tacrolimus

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What is tacrolimus?

Tacrolimus, also known as FK506, is an immunosuppressive medication that is sometimes prescribed for individuals with autoimmune myasthenia gravis (MG). It is manufactured as a capsule. Oral tacrolimus has both immediate-release and extended-release forms. You can purchase tacrolimus in generic form or by brand names such as Astagraf XL®, Envarsus XR®, Hecoria® and Prograf®. Tacrolimus is also available as a solution for injection.

 

How does tacrolimus work?

Much like the drug cyclosporine, tacrolimus inhibits calcineurin and suppresses the autoimmune response that is responsible for causing the fluctuating and fatigable muscle weakness of MG.

 

How soon should I see a response?

Although some people have reported improvement in as little as 10 days, more commonly you may expect to notice a gradual improvement of myasthenic weakness after one month of taking tacrolimus.  Other people with MG may take a longer time to see a response. Similar to other immunosuppressive medications, some patients may not experience a benefit from its usage.  

 

How is tacrolimus taken?

Tacrolimus must be taken exactly as directed by your doctor. Never increase, decrease, or stop taking it without checking with your doctor. The immediate-release form is taken in divided doses (usually 12 hours apart), and the extended-form is taken once daily (usually in the morning). Swallow capsules whole and do not break or chew them. Tacrolimus needs to be taken on an empty stomach (at least 1 hour before or 2 hours after a meal) to assure good absorption as food reduces its bioavailability. Alcohol modifies the absorption of tacrolimus, and tacrolimus should not be taken with alcoholic beverages. Finally, grapefruit juice should be avoided as it may alter the metabolism of tacrolimus.

 

It is important that all of your health care providers know you are taking tacrolimus because it can interact with other medicines, causing undesirable effects. The list below will help you and your physician know which medications may produce problems while you are taking tacrolimus.

 

Drugs that may cause more toxicity when combined with tacrolimus

  • Antibiotics –levofloxacin (Levaquin®)
  • Potassium sparing diuretics – spironolactone (Aldactone®)
  • Immunosuppressants – fingolimod, leflunomide, natalizumab
  • Miscellaneous – clozapine (Clozaril®)

 

Drugs that may modify tacrolimus effectiveness

  • Antibiotics – azithromycin (Zithromax®), erythromycin, rifampin (Rifadin®)
  • Antifungal medications: fluconazole (DIflucan®), itraconazole (Sporanox®), ketoconazole (Nizoral®), voriconazole (Vfend®)
  • Miscellaneous – colchicine, corticosteroids, Schisandra, St. John’s Wort
  • Anticonvulsants – phenytoin (Dilantin®)

 

What will my doctor want to know before prescribing tacrolimus?

Since tacrolimus is a strong medicine, you and your doctor and must consider its risks and benefits. Your doctor will ask you about:

  • Current medications and treatments.
  • History of any allergies.
  • History of high blood pressure.
  • History of liver or kidney disease.
  • History of diabetes.
  • Any recent infections or immunizations.
  • Pregnancy, planning a pregnancy or breastfeeding.

 

What are some special considerations when taking tacrolimus?

Your physician will check blood tests regularly to monitor for significant changes. BUN and serum creatinine are checked before beginning tacrolimus, then once a month for the first 3 months, and then every 3 months while taking tacrolimus. Tacrolimus blood levels are performed weekly for the first month after starting, and periodically thereafter, especially after a change in dose. Trough blood levels are drawn, just before the next dose is due.  A trough level measures the lowest concentration of tacrolimus in your bloodstream and is monitored to ensure that a therapeutic level is maintained.  Blood pressure and renal function should also be monitored closely when taking tacrolimus.

 

Tacrolimus may cause unwanted side effects, some of which may be serious. Other side effects may go away as your body adjusts to the drug. It is important to notify your health care providers about side effects. Allergic reactions can be life threatening and you should get emergency help at once. These include hives; severe itching; tightness in the neck or chest; trouble breathing; or swelling of the lips, tongue or throat. Also serious, are blood in the urine, confusion and seizures. Tacrolimus may cause tremors, worsen diabetes or cause a low magnesium level in the blood.

 

Tacrolimus may cause increased susceptibility to bacterial, viral, fungal, and protozoal infections, including opportunistic infections and the possible development of malignancies such as lymphoma or skin cancer.  It is important that you talk over any concerns you may have about tacrolimus with your doctor.

Therapeutic Plasma Exchange (TPE)

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What is therapeutic plasma exchange?

Therapeutic plasma exchange is a treatment for antibody-mediated diseases like MG.  During this procedure, blood is separated into cells and plasma (liquid). The plasma portion is removed and typically replaced with either a human-derived sterile fluid called albumin or plasma. The procedure is often referred to as plasma exchange (PLEX) or plasmapheresis.

 

Why would I have therapeutic plasma exchange?

Therapeutic plasma exchange may be recommended to:

  • Stabilize a rapid decrease in muscle strength, including significant difficulties in speaking, swallowing and breathing
  • Optimize MG status before surgery
  • Add to present treatment if current forms of therapy are providing insufficient disease control

How does therapeutic plasma exchange work in MG?

The process removes the antibodies that are interfering with function of the neuromuscular junction.  Removal of these pathogenic antibodies allows for restoration of normal activity at the neuromuscular junction, resulting in improved muscular strength.

 

How many therapeutic plasma exchanges will I need and where will it be done?

The number of treatments depends on whether it is for preventative treatment or for a crisis.

 

Preventative Treatment

Your neurologist will work with you and the apheresis team to determine the number of treatments needed based on your MG status and signs/symptoms. Treatment options vary from every 24 to 72 hours for three to six treatments, or single treatments weekly, bi-weekly or monthly until signs and symptoms diminish.

Crisis: If experiencing an MG crisis, therapeutic plasma exchange can significantly improve signs and symptoms. The health care team will assess your neurologic status, muscular strength, and vital signs to assist in determining the number of treatments needed.  In general, a patient with MG crisis receives a more aggressive therapeutic intervention and will have therapeutic plasma exchange procedures every 24 to 48 hours for 5 to 6 treatments until you are stable.

Therapeutic plasma exchange can be administered both in the hospital and in an outpatient setting.  The procedure can be completed by two different delivery systems:

  • Peripheral venous access if you have suitable arm veins.
  • Placement of a double lumen central venous catheter or subcutaneous port.

Overnight hospitalization is sometimes recommended for central venous catheter placement and initiation of therapeutic plasma exchange.  Generally, a tunneled catheter or port is needed to minimize risk of line infections if long-term therapeutic plasma exchange treatment is anticipated and peripheral venous access is not possible. 

 

What type of venous access is required?

In the case of therapeutic plasma exchange using peripheral veins, a needle will be inserted into a vein in each arm and removed after each treatment. In rare instances, only one arm may be used.  If your arm veins are unsuitable to use, interventional radiologists or surgeons will place an indwelling, double lumen catheter into a large vein in your neck or shoulder under local anesthesia.  This is also known as a central catheter or central line. Such indwelling catheters can remain in place for many months with proper care.  In rare, urgent situations, catheters are placed in the groin, but these are temporary due to high risk of infection and because they interfere with walking.  They are usually reserved for inpatient therapeutic plasma exchange. You will receive instructions from your team to prepare for indwelling catheter placement. Be aware of the difference between internal and external catheters when showering and submerging under water. Maintenance and proper cleaning is extremely important to avoid risk of infection.  Another option for long-term vascular access is a subcutaneous port.  These devices are completely embedded under the skin and so have lower risks of infection and incidental damage compared to catheters.  However, a port requires a slightly larger procedure during placement and is not ready for immediate use; thus, this device may or may not be a suitable vascular access option depending on your specific clinical situation.

 

What should I expect during therapeutic plasma exchange?

Unless the physician has instructed otherwise, it is important to eat before the therapeutic plasma exchange and not skip meals. During therapeutic plasma exchange, you may drink fluids. You should empty your bladder prior to the procedure and ask the nurse for a bedpan or urinal if needed during the therapeutic plasma exchange procedure. If you have peripheral venous access, you will need to keep both arms outstretched and still.  If you have an indwelling catheter, you will be able to move your arms during the procedure.  Wearing comfortable clothing with loose fitting sleeves that pull easily above your elbows will make it easier to place the needles in each arm for peripheral access. Wearing comfortable clothing with a loose-fitting shirt is important if you have an indwelling catheter to provide easy access to the site. Bringing something to read, watch, or listen to will help you pass the time. You may experience some coldness during the treatment. If this happens, ask your treatment staff to provide you with a warm blanket.

 

How long does therapeutic plasma exchange take?

The time spent on the machine may take from one to three hours. This depends upon many factors such as your weight, height, the amount of plasma to be exchanged, the catheter type (peripheral or central), and catheter performance.

How will I feel after my therapeutic plasma exchange?

 

Many patients feel fine after the procedure. Others may feel tired or have lightheadedness. If the procedure is done on an outpatient basis, then someone should drive you home.

How soon will the treatment work?

 

Compared to other treatments, therapeutic plasma exchange works quickly to increase strength. You are likely to notice improvement after the first few procedures.

How long will the improvement last?

 

Effectiveness can vary, but most people who have received five therapeutic plasma exchanges over 1 to 2 weeks can remain stronger for one to two months.  After that time, weakness can recur due to the pathogenic antibodies returning to pre-treatment levels in the bloodstream and at the neuromuscular junction.

What are the possible adverse effects?

 

Common adverse effects may include a change in heart rate or blood pressure, sweating, or feelings of faintness, dizziness, coldness, or abdominal cramps. Additionally, tingling associated with the mouth, eyes, fingers or toes can occur.  Rare, adverse effects may include bleeding (a result of removal of clotting factors) and a possible allergic reaction such as itching, wheezing, and rash to the solutions used during the procedure. Infection or clotting can occur with vascular access devices placed for therapeutic plasma exchange, which often then necessitates removal of the device.  Most individuals tolerate therapeutic plasma exchange very well and have no issues during their treatments.

 

I am anxious about having therapeutic plasma exchange! 

It is normal to feel nervous about any new procedure. Anxiety about therapeutic plasma exchange - especially during the first few treatments - is only natural and can produce hypersensitivity to new sensations that will go away once you become more comfortable with the procedure. Helpful ways to prepare and alleviate fears may include speaking to someone who has been treated with therapeutic plasma exchange and discussing concerns with your physician and the apheresis team. It can help to ask the team to explain what they are doing and why during the procedure. Contact MGFA if you would like to connect with someone else with MG who has experience with therapeutic plasma exchange.

 

I am a family member/ friend of a person with MG, what do I need to know?

It can be very comforting for a person going through therapeutic plasma exchange to have someone there as company, and to ask about what is happening through the procedure.  In preparing for possible emergencies, it is important to know that therapeutic plasma exchange (or IVIg) may be started right away for a person with MG who is in full-blown crisis - having difficulty swallowing, speaking, breathing, and even needing assistance with respiration using a mechanical ventilator or other device.  This can be scary for everyone, especially for YOU as you find yourself having to take charge of working with the health care team.  The number of therapeutic plasma exchange treatments will vary, however, it is crucial to know what to expect. What you are seeing on the monitor (heart rates, respiration rates, blood pressures, et cetera), and the role mechanical ventilators and other devices play in the patient’s recovery. It can be intimidating to see your family member connected to a machine, but it helps to know this process may be the fastest way for a person with MG to regain strength. Be prepared for breathing trials that can be uncomfortable for your loved one, but are important tests to determine their strength prior to removing any breathing device.
 

Speak to your loved one regularly; explain what is happening and sound as calm and confident as you can. Even if he/she is unable to answer or is sedated, hearing your voice can be very soothing. In your role as advocate, ask questions about what you do not understand so you can be at ease about your loved ones’ care. Remember to take care of yourself throughout a crisis as you will play a key role in the days and weeks to come. The real work begins when the patient is breathing without any assistance and coping with everything that just transpired. You will need to be both physically and mentally strong for your loved one.

Thymectomy

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The following are answers to some of the most common questions asked when a thymectomy is being considered for adult and younger patients with autoimmune myasthenia gravis (MG).

 

The answers supplied below are presented in general terms as background information only and should not be used to make specific decisions. Since each patient’s situation is unique and the types of thymectomy being performed vary, it is essential that you discuss in detail these and all other questions about the surgery with your MG specialist and surgeon.

 

What is a thymectomy and why is it performed?

A thymectomy is the surgical removal of the thymus gland. The thymus has been demonstrated to play a role in the development of MG. It is removed in an effort to improve the weakness caused by MG, and to remove a thymoma if present. About 10% of MG patients have a tumor of the thymus called a thymoma. Most of these tumors are benign and tend to grow very slowly, however occasionally, a tumor is malignant (cancerous).  Every person diagnosed with MG should have a CT scan of the chest to check for a tumor.

 

What is the function of the thymus? Is its removal harmful?

The thymus gland plays a major role in the development of the body’s immune system. Its job is to train immature T-cells to develop into mature T-cells which are then are circulated in the body to help activate the immune system’s B-cells to fight infections. The thymus gland enlarges throughout childhood and starts shrinking during puberty. By the time adulthood is reached, the thymus gland’s function is no longer needed. Removal of the thymus in the treatment of MG in adulthood does not affect the immune system thereafter.

 

Exactly where is the thymus located?

The thymus is located in the front portion of the chest (anterior mediastinum) with “finger-like” extensions into the neck and consists of multiple lobes (two to five or more). In addition, varying amounts of thymic tissue may be present in the fat surrounding the lobes, both in the neck and chest.

 

Who should have a thymectomy?

A thymectomy is frequently recommended for patients under the age of 60 with moderate to severe MG weakness. However, it is recommended for patients of any age who present with a thymoma or thymic tumor. It is sometimes recommended for patients with relatively mild weakness, especially if there is weakness of the respiratory (breathing) or oropharyngeal (swallowing) muscles. A thymectomy is usually not recommended for patients with weakness limited to the eye muscles (ocular myasthenia gravis).

In a recently completed randomized trial of extended transsternal thymectomy in patients without thymoma, patients aged 18 to 45 and who had a positive AchR blood test and who had presented with generalized symptoms within the last 5 years prior to the surgery were found to have the greatest benefit from thymectomy. These patients had reduced hospitalizations due to MG exacerbations, and reduced requirements for prednisone and other immunotherapies.  Older patients were also randomized in the study, but their numbers were too small to make definitive statements about the benefits of thymectomy above age 45.  [See New England Journal of Medicine, August 11, 2016, Volume 375, No. 6, Randomized Trial of Thymectomy in Myasthenia Gravis, G.I. Wolfe; H.J. Kaminski, et al.]

 

What should I expect as I consider a thymectomy?

When a thymectomy is being considered, you will be referred to a surgeon. It is important to choose a surgeon experienced in performing thymectomies for patients with MG. The surgeon will review your clinical records, examine you, discuss your surgical options  and make a recommendation. The surgeon also explains the anticipated pre- and post-operative courses, possible complications, and the anticipated results. You, in consultation with the neurologist and surgeon, will then make a decision:  whether or not to proceed with a thymectomy and if yes, the type of surgery to be used.

 

What are the goals of a thymectomy?

The neurological goals of a thymectomy are significant improvement in the patient’s weakness, reduction in the medications being employed, and ideally a permanent remission (complete elimination of all weakness and off all medications). A thymectomy is usually not used to treat active disease but rather it is believed to improve long-term outcome. Results may not be seen for one to two years or more after the thymectomy.

 

How is the surgery performed?

There are three basic surgical approaches explained in the paragraphs below, each with several variations. Regardless of the technique employed, the surgical goal is to remove the entire thymus. Many believe this should include removal of the adjacent fat; others are less sure.

 

Transsternal Thymectomy

  • Incision: Vertical (lengthwise) on the anterior chest; the sternum (breastbone) is “split” vertically.
  • Thymus Removal: The chest and neck portion of the thymus are removed through this incision.
  • Extended Form: The fat located in the front part of the chest next to the thymus, as well as the thymus, is removed. Complete removal of all tissue containing thymus is believed ensured.  This is the approach that was used in the randomized trial mentioned above. 
  • Combined Chest and Neck: A few MG Centers add a formal neck dissection to the sternal technique to also ensure the removal of all the thymus in the neck.
  • Thymoma: Most recommend the transsternal approach for removal of a thymoma.

 

Transcervical Thymectomy

  • Incision: Transverse (horizontal) across the lower neck.
  • Thymus Removal: The chest portion of the thymus is removed through this incision.
  • Extended Form: The “extended” form allows improved exposure of the thymus in the chest with more complete removal of the thymus. Although the adjacent fat is also removed, less is removed than in the extended transsternal thymectomy.

 

Videoscopic (VATS) Thymectomy

  • Incision: Several small incisions on the right or left side of the chest.
  • Thymus Removal: Fiber-optic instruments are used. These are small flexible tubes with a light at the end through which small instruments can be passed. The amount of thymus and fat removed is variable.
  • Extended Form: In the “VATET” form, incisions are made on both sides of the chest, as well as in the neck, for “more complete” removal of the thymus.

 

What are the results of a thymectomy?

Many neurologists experienced in the treatment of MG are convinced that a thymectomy plays an important role in the therapy of MG, although the benefit is variable. The randomized trial of thymectomy mentioned above has provided evidence to back up this conviction, at least in AchR positive patients with generalized MG.

 

In general, most patients begin to improve within one year following a thymectomy and a variable number eventually develop a permanent remission (no weakness and no medication). Some physicians believe the remission rates after surgery are in the 20-40% range regardless of the type of thymectomy performed. Others believe that the remission rates following the more extensive procedures are in the 40-60% range five or more years after the surgery.

 

It is important to note that rigorous scientific studies are needed to resolve the debate concerning the best method of performing a thymectomy in the treatment of MG patients.

 

What type of thymectomy should I have?

Since there is no universal agreement, or unequivocal proof, as to which type of thymectomy is best, it is difficult for patients to decide what is best for them. There is, however, general agreement that the entire thymus should be removed and that the patient should select the procedure that ensures as much as possible that this is accomplished. Some surgeons believe that all the surrounding fat should be removed as well, because it frequently contains microscopic (very small) amounts of thymus; others believe this may not be necessary.

 

There is growing evidence that “minimally invasive” procedures (transcervical and videoscopic) are as effective as more invasive approaches.  The evidence for this is mainly through retrospective comparisons of patients who underwent different types of surgery during different eras in the last two to three decades.  As of yet, there are no prospective, randomized studies comparing different surgical techniques which would provide a higher level of evidence. 

 

Since there is no absolute proof as to which type of thymectomy is the procedure of choice, it is up to you to become fully informed, review the evidence presented by the neurologist and surgeon caring for you, and perhaps obtain additional consultation (second or even third opinion). Again, the key to the optimal outcome is to remove as much thymic tissue as possible in the safest way possible for a particular patient.  It is important that you have your questions answered, and confidence in your medical team and the decisions about your plan. 

 

What can the MG patient expect in the pre-operative, anesthesia and post-operative periods?

In general, MG Centers have developed protocols for the care of MG patients and have a team of neurologists, surgeons, pulmonologists, intensive care and respiratory care specialists, nurses and anesthesiologists caring for MG patients undergoing a thymectomy.  To ensure that you are fully prepared, ask for time to discuss all aspects of the pre-and post-operative care and anesthesia with the surgeon, anesthesiologist and neurologist. 

 

To reduce the risks of post-operative respiratory complications or the post-operative need for prolonged respiratory support with a ventilator (breathing machine), your doctor may require pre-operative plasma exchange (PLEX) or intravenous immunoglobulin (IVIg), and some require immunosuppressive therapy as well. If you are taking pyridostigmine (Mestinon) your medical team will advise on what to do both in the weeks before, and the day of and the days after surgery.  The surgical team will also advise on all medications you may be taking---not just for MG, but for other conditions such as blood pressure, pain (like aspirin, NSAIDs, etc.).  Be sure to have these discussions. 

 

The anesthesia for patients with MG is similar to the anesthesia given to other patients. An endotracheal tube (tube in the windpipe) is inserted after you are asleep. Muscle relaxing drugs, however, are usually avoided. You may or may not be extubated (removal of the endotracheal tube) upon awakening, depending on your strength. If the endotracheal tube is not removed on awakening, the tube will be attached to a ventilator.

Ordinarily after the surgery, you will go to a Recovery Room, Respiratory Care Unit, or Intensive Care Unit depending on each hospital’s method of taking care of MG patients following surgery. A ventilator may be required depending on the type of operation and the severity of your weakness. As soon as the breathing tube has been removed, you will be asked and helped to deep breath and cough frequently to keep the lungs clear of secretions. One or two chest tubes (small tubes exiting the chest and attached to drainage bottles) are usually used after the transsternal and videoscopic operations, and removed soon after surgery.

 

Medications used to manage MG before surgery are usually continued after surgery. The neurologist will decide how to taper your medications after surgery in subsequent follow-up appointments.

 

Pain is minimal following transcervical thymectomy and usually mild following videoscopic thymectomy, although some patients have reported late pain. The pain associated with transsternal thymectomy is temporary and well controlled with medication and gradually resolves within 3-5 days. Patients typically require minimal pain medication on hospital discharge. If your pain is not well-controlled, talk with your doctors about options. 

 

The length of time in the hospital will vary depending on the type of surgery and your overall weakness. In most cases you will be ready to go home in a few days to a week. Your preoperative medications, immunosuppression and other forms of therapy are usually resumed after surgery for variable periods of time depending on the MG symptoms and the neurologist’s recommendations.

 

When can I return to my usual activities?

It is hard to predict the recovery time for any individual patient.  And the return to work, school and other responsibilities and activities will also vary—as certainly some jobs and life responsibilities are more physically demanding than others.  It may be best to plan for the worst (when working with both health and disability insurance) and still hope for the best. Your physician can provide an estimate, based on your expected responsibilities, as well as your normal level of weakness and the surgical plan—but no one really knows how any given person will react to and recover from surgery—especially someone with MG. 

 

A patient who does heavy lifting or construction work, or is a school teacher or hospital nurse on his/her feet all day, may need to be off work longer than someone who has a desk  job. And the mom or dad whose day job is taking care of a toddler may need extra help until he/she is able to safely lift 25-30 pounds.  It is also hard to predict the fatigue factor with MG.  It is better for those who are employed and planning to return to work to ask your physician to write for a longer time off for your short-term disability.  If you feel great and are ready to go back, no one will argue if your doctor reduces the needed time off.    It is encouraging to note that most patients have very few problems after the surgery and are able to return to their usual pre-operative activities.

 

Will my insurance pay for the surgery?

Health insurance companies do pay for thymectomies. Since there may be questions concerning insurance coverage with specific surgeons and specific institutions, it is a good idea to check with your insurance company as soon as a thymectomy is being considered to make sure that the coverage is in order. Some insurance companies may require additional consultation and some type of prior authorization. In some instances, letters from the neurologist and surgeon will be required to defend the procedure selected.

A World Without MG