Facts About Myasthenia Gravis, Lambert-Eaton Myasthenic Syndrome & Congenital Myasthenic Syndromes

Updated December 2009 Dear Friends:

everal years ago, I started to feel weak procedures — that will help you discuss Sand tired all the time, especially in my your options with a physician. neck. Basic functions that I’d always taken The Association can for granted — like chewing, swallowing and help guide you through this process in many talking — suddenly became difficult. One of ways. Doctors at an MDA clinic near my my began to droop and my arms felt home diagnosed my MG and established an weak. appropriate course of treatment. I visit the I hoped these were signs of some temporary clinic regularly, and they continue to adjust illness, but my symptoms continued and, the treatment to any changes in my needs. finally, physicians discovered I had myas- The local MDA staff were there for me on thenia gravis. I worried about how having the day I was diagnosed and have been this disease would affect my future, my available for support ever since. general health, my family and my career as Since my diagnosis, I’ve continued to work, a pediatric psychotherapist, which requires and my husband and I have raised two chil- a lot of talking with clients and health care dren who are now adults. I lead a very active professionals. life and enjoy community service, gardening, Now, I don’t worry so much — at least not sailing, travel and the arts. about MG. If you or someone you love has At times, I’ve had to make adjustments. just received a diagnosis of MG, you’ll learn, When I’ve had episodes of extreme weak- as I did, that a variety of treatments can be ness, my family has been there to help me. used to control it. By learning more about I’ve cut back some of my hours at work, and MG and by partnering with your physician, accommodations have been made at work to you’ll discover that you can become an help me conserve my energy. active participant in your treatment plan, adjust to your diagnosis and take control in Judy Walsh Changes at work can be challenging but maintaining the quality of your life. remember: If you have lasting or recurring disability from MG or any other disease, the This pamphlet will provide you with essential law entitles you to reasonable workplace information about the symptoms of MG and accommodations and equal employment the best treatments for it — which are differ- opportunities. ent for each person. You’ll find out that MG causes progressive and in And remember that MDA is here to help. the body’s voluntary muscles, without affect- If you have questions not answered in this ing the musculature of the heart. Although pamphlet, you can find information in MDA’s it can weaken the muscles that control other publications or on its website, or you breathing, MG usually doesn’t shorten life can ask a member of your local MDA staff. expectancy. With the help of the MDA staff and others who understand your illness, this is a jour- The pamphlet also contains information ney that you don’t have to take alone. about two types of disease related to MG — Lambert-Eaton myasthenic syndrome and congenital myasthenic syndrome. Some of the treatments that work against MG also Judy Walsh work against LEMS and some types of Providence, Rhode Island CMS. You’ll learn details about these treat- ments — from drugs to surgery and other

2 MG • ©2011 MDA What Is Myasthenia Gravis? yasthenia gravis (MG) causes weak- This booklet provides essential informa- M ness that gets worse with exertion tion about MG and two related diseases and improves with rest. The disease first that affect the , appeared in medical reports in 1672, but Lambert-Eaton myasthenic syndrome didn’t earn its name, which literally means (LEMS) and congenital myasthenic syn- “grave muscular weakness,” until the drome (CMS). 1880s. What causes MG? Physicians in 19th-century Germany, the The immune system normally defends first to begin systematic studies of the the body against diseases, but sometimes disease, noted that it produces weakness it can turn against the body, leading to that fluctuates but generally progresses an . MG is just one with time. Lacking crucial insights into of many autoimmune diseases, which the properties of nerve and muscle, they include arthritis and type I diabetes. weren’t able to do much for their patients, many of whom lost strength rapidly and In all of these diseases, an army of eventually died from respiratory failure. immune cells that would normally attack Even in the early 20th century, the mortal- bacteria and disease-causing “germs” ity rate of MG was around 70 percent. mistakenly attacks cells and/or proteins that have essential functions in the body. Fortunately, over the past 100 years, the In most cases of MG, the immune system origins of MG have gradually unfolded, targets the — a and the outlook for people with the disease protein on muscle cells that’s required for has improved dramatically. muscle contraction.

MG is an autoimmune disease — a (See illustration on page 4.) disease that occurs when the immune system attacks the body’s own tissues. In At the normal neuromuscular junction, a MG, that attack interrupts the connection nerve cell tells a muscle cell to contract by between nerve and muscle — the neuro- releasing the chemical acetylcholine (ACh). muscular junction. Muscles that control ACh attaches to the ACh receptor — a pore In myasthenia gravis, the eyes, face, neck and limbs are com- or “channel” in the surface of the muscle often first appears in the muscles of monly affected. cell — twisting it open and allowing an the face, neck and jaw. The arm and leg inward flux of electrical current that triggers muscles are affected later. Thanks to this understanding of the muscle contraction. These contractions mechanism behind MG, physicians can enable someone to move a hand, to dial the now treat it with drugs that suppress telephone, walk through a door or complete the immune system or boost the signals any other voluntary movement. between nerve and muscle. Surgeries and other procedures are also helpful in many About 85 percent of people with MG have cases. against the ACh receptor in their blood. The antibodies (Y-shaped Physicians now estimate that, when MG is missiles that immune cells called B cells properly treated, the mortality rate is near use to attack bacteria and viruses) target zero. Most people with the disease are and destroy many of the ACh receptors able to manage their symptoms and lead on muscle. Consequently, the muscle’s active lives, and a few experience remis- response to repeated nerve signals sion lasting many years. declines with time, and the muscles become weak and tired.

3 MG • ©2011 MDA About 15 percent of people with MG plasia. When the doesn’t work are seronegative for antibodies to the properly, the T cells might lose some of ACh receptor, meaning the antibodies their ability to distinguish self from non- aren’t detectable in their blood (serum). self, making them more likely to attack the Recently, it’s been discovered that a large body’s own cells. fraction of these people have antibodies to muscle-specific kinase (MuSK), a protein Who gets MG? that helps organize ACh receptors on the MG affects two to seven out of every muscle cell surface. 10,000 people in Western countries. It occurs about one and a half times more Scientists don’t know what triggers most often in women than in men. autoimmune reactions, but they have a few theories. One possibility is that certain The disease can appear at any age, but the viral or bacterial proteins mimic “self- average age of onset in females is 28; in proteins” in the body (such as the ACh males, it’s 42. In about 10 percent of cases, receptor), stimulating the immune system MG begins in childhood (juvenile onset). to unwittingly attack the self-protein. Genetic susceptibility appears to play a There’s also evidence that an immune role in MG and in other autoimmune dis- system gland called the thymus plays a eases. Most studies suggest that if you role in MG. (See illustration on page 5.) have a relative with an autoimmune dis- Located in the chest just below the throat, ease, your risk of getting an autoimmune the thymus is essential to the develop- disease is increased — the closer the ment of the immune system. From fetal relative, the higher the risk. Even for iden- life through childhood, the gland teaches tical twins, however, that risk is relatively immune cells called T cells to recognize small. Most studies suggest that when self from non-self. one twin has an autoimmune disease, the other has less than a 50 percent chance of About 15 percent of people with MG have getting the same disease. a thymic tumor, called a , and another 65 percent have overactive thymic Also, people who already have one auto- cells, a condition called thymic hyper- immune disease have a greater risk of

Myasthenia gravis occurs when the immune system makes antibodies that destroy the ACh receptor (AChR), a docking site Packets of ACh for the nerve chemical acetylcholine (ACh). Some treatments block Nerve cell (AChE), an enzyme that breaks down ACh, while others target the MG more often affects women than immune system. ACh AChE men and begins at an earlier age in women.

Muscle cell AChR

4 MG • ©2011 MDA developing another one. It’s esti- over the head, rise from a sitting mated that 5 to 10 percent of people position, walk long distances, climb with MG have another autoimmune stairs or grip heavy objects. disease, which appeared before or after the onset of MG. The most In severe cases, weakness may common of these are autoimmune spread to muscles in the chest that thyroid disease, control breathing. and systemic erythematosus A Disease course (a disease that affects multiple Weakness and fatigue in MG tend to Bacteria organs). fluctuate from day to day, and even during a single day. People with the What happens to disease are often strongest in the Antibodies someone with MG? morning after a full night’s sleep and Weakness and fatigue weakest in the evening. B MG weakens and the body’s Over a longer term, the symptoms Nerve cell voluntary muscles (those we can of MG usually progress, reaching move at will). It doesn’t damage the maximum or near-maximum severity musculature of the heart or the gas- within one to three years of onset in trointestinal tract. most people. In about 15 percent of Muscle cell people, the disease remains ocular, Early in its course, MG tends to but in most, it becomes oculobulbar Normally (A), the immune system releases antibodies affect the muscles that control to attack foreign invaders, such as bacteria. In autoim- or generalized. If the disease remains movement of the eyes and - mune diseases (B), the antibodies mistakenly attack a ocular for three years, it usually person’s own tissues. In myasthenia gravis, they attack lids, causing ocular weakness. doesn’t become generalized. and damage muscle cells; in Lambert-Eaton myasthenic Consequently, a partial of syndrome, they attackA nerve cells that send messages to muscle. eye movements (), Weakness serious enough to require double vision (), and droopy a wheelchair is almost unheard of BACTERIA eyelids () are usually among in MG. Most people, when properly the first symptoms of MG. treated, find they can remain physi- cally active. Weakness and fatigue in the neck and jaw also can occur early in MG. Remission, a reversal of some or all This bulbar weakness — named for symptoms, occurs in about 20 per- the nerves that originate from the cent of people with MG. Usually, the bulblike part of the brainstem — can remissions are temporary, with an ANTIBODIES make it difficult to talk, chew, swal- average duration of five years, but low and hold up the head. some people experience more than one remission during their lifetimes. Bulbar weakness tends to give A few people have experienced speech a slurred, nasal quality. It The thymus, a small gland in the upper apparently permanent remissions, can also lead to frequent choking chest, seems to play a role in myasthenia lasting more than 20 years. gravis. spells, and make eating unpleasant B and tiresome. Compared to adult-onset MG, juve- nile MG tends to progress more In generalized MG, weakness tends slowly and has a higher incidence to spread sequentially from the face of remission. Historically, many and neck to the upper limbs, the Nerve Cell children given diagnoses of juvenile NERVE CELL hands and then the lower limbs. It MG turned out to have a CMS (see may become difficult to lift the arms page 11). A

5 MG • ©2011 MDA C B Muscle Cell MUSCLE CELL Drugs and other concerns of the drug types mentioned on this page. Many prescription drugs can unmask or If you have MG, you should have these worsen symptoms of MG. These include: conditions monitored by a physician, and if you experience labored breathing • muscle relaxants used during surgery or unusual weakness, you should seek immediate medical attention. • aminoglycoside and quinolone antibiotics In rare cases, pregnancy appears to trigger • cardiac anti-arrhythmics the onset of MG. In women who already • local anesthetics have MG, pregnancy can cause a worsen- ing of symptoms (usually after birth, but Juvenile MG progresses more slowly • magnesium salts (including milk of than the adult form, and more often sometimes during the first trimester); an goes into remission. magnesia) improvement (usually during the first tri- mester); or no change, with about equal When taking a new prescription drug for the likelihood. These trends aren’t consistent first time, it’s a good idea to consult your from one pregnancy to the next. doctor about its possible effects on MG. Also, you might want to keep a Medic Alert Some for MG (see “How is bracelet or card handy to inform emergency MG treated?” on this page) are safe to use medical personnel that you have MG and during pregnancy and nursing, but some that certain drugs can be harmful to you. others aren’t recommended. If you’re plan- ning to become pregnant, you should con- Overexertion, emotional stress, infec- sult your physician, and if you’re a nursing tions (from tooth abscesses to the flu), mother, consult your child’s pediatrician. menstruation and pregnancy can also lead to increased weakness in MG. (See Between 10 and 20 percent of babies born “Pregnancy,” this page, for more informa- to mothers with MG develop transient neo- Adults with MG, like this woman, have tion.) fluctuating symptoms, and manage natal MG, probably because the antibod- their lives by minimizing stress and ies that cause MG can pass through the conserving energy. Myasthenic crisis placenta. Symptoms (such as feeble cry, Especially in people with bulbar or respi- feeding difficulties or respiratory weakness) ratory symptoms, MG can sometimes are often detected within hours to days worsen to the point of myasthenic crisis, after birth, and decreased movement may an extreme episode of weakness that cul- be detected inside the womb. minates in respiratory failure and the need for . In some cases, As the name implies, transient neonatal the respiratory muscles themselves give MG is only temporary. Most babies require out, and in others, weakness in the throat and supportive care, but usu- muscles causes the airway to collapse. ally recover completely within two months after birth. Permanent weakness or recur- When MG is properly treated, crisis is very rence of MG later in life is extremely rare. rare. And when crisis does occur, it has a good rate of recovery, thanks to the wide range of treatments for MG and the quality How is MG treated? of respiratory care at most hospitals. Many drugs and procedures are available Pregnancy can worsen a woman’s for treating MG, each with distinct advan- Sometimes, myasthenic crisis can occur symptoms of MG, and her child may be tages and disadvantages. Drugs known born with transient neonatal MG — a without warning, but it often has an iden- as inhibitors provide relief temporary condition. tifiable trigger, such as fever, respiratory from symptoms by blocking the action of infection, traumatic injury, stress, or one acetylcholinesterase and increasing the

6 MG • ©2011 MDA amount of acetylcholine at the neuromus- They’re not as fast-acting as cholines- cular junction. terase inhibitors, but they’re faster than some other immunosuppressants, produc- Immunosuppressant drugs can be used ing improvement within weeks to months. to attack the disease at its source, but They’re also relatively inexpensive. they increase susceptibility to infectious diseases and most of them carry other A disadvantage of corticosteroids is that potentially serious side effects. they can produce many side effects — some of them potentially serious — The benefits and risks of these treatments including osteoporosis (weakening of must be weighed against each other and bones), mood disturbances, gastrointes- the needs of the patient. Your doctor or tinal problems, weight gain, high blood MDA clinic director can help you determine pressure, cataracts and stunted growth which treatments are appropriate for you. (in children). For many people, these side Cholinesterase inhibitors effects can be managed with other thera- pies; for example, bisphosphonate drugs These drugs, also known as anticholines- can be used to prevent osteoporosis. terases, have been used against MG since the early 1990s, and can produce relief For others, corticosteroids are used as a from symptoms within minutes. The one first-line defense against MG, then gradually most commonly used is tapered off, and supplemented or replaced Many patients with MG, including tele- (Mestinon). vision actress Suzanne Rogers, have with slower-acting immunosuppressants achieved remission with , that have fewer side effects. Most of these Cholinesterase inhibitors boost ACh levels combined with medication. other drugs were developed to prevent the not only at the neuromuscular junction, rejection of transplanted organs, but have but also in the autonomic nervous sys- since been co-opted for use against MG and tem (which controls involuntary bodily other autoimmune diseases. functions). Sometimes the drugs can cause diarrhea, abdominal cramps and/ (Imuran). This was the first or excessive saliva. To minimize these non-steroid immunosuppressant to come side effects, your physician might lower into widespread use against MG, in the the dose of cholinesterase inhibitors or 1970s. It acts more slowly than cortico- prescribe , which blocks the ACh steroids, producing improvement after receptors on nerve cells. three to six months, and usually has few side effects. Occasionally, however, it In rare cases, cholinesterase inhibitors can produce serious side effects, includ- prove sufficient for managing MG, but ing inflammation of the pancreas, liver most people also require immunosup- toxicity, bone marrow suppression and pression — treatment that restrains the Various drug treatments are effective possibly an increased risk of cancer. in restoring strength in MG, but side actions of the immune system. effects should be discussed when Mycophenylate mofetil (CellCept). CellCept they’re being considered. This woman Immunosuppressant drugs is a relatively new immunosuppressant, got good results from cyclophospha- Corticosteroids. These drugs (which mide. but so far it’s shown promising results include and prednisolone) against MG in clinical trials. In two small reproduce the actions of corticosteroid trials completed in 2001, about 65 per- hormones, which are made by the cortex cent of MG patients experienced gains in (outer layer) of the adrenal gland. They strength or a reduced need for prednisone have broad anti-immune and anti-inflam- after taking CellCept for several months. matory effects, making them powerful treatments for MG. More recent analyses have shown that some people take longer to respond to the

7 MG • ©2011 MDA drug, but that nearly 75 percent eventu- specific antibody (immunoglobulin) that ally show improvement, with occasional might work by dialing down the immune relatively nonserious side effects such as system’s production of its own antibodies, stomach upset, flulike symptoms, rash much as warm air tells a thermostat to and tremor. stop pumping out heat.

Cyclosporine (Neoral, Sandimmune). This These treatments bring about fast, but is a useful, relatively fast-acting treatment short-lived relief from MG, and are mostly for MG, but it may have side effects used until other medications take effect, including increased blood pressure, prior to surgery or for myasthenic crisis. abnormal kidney function, unwanted body However, some people receive regular hair and stomach upset. or IVIg as a supplement to immunosuppressant drugs. Cyclophosphamide (Cytoxan, Neosar). This drug is considered effective against How is MG diagnosed? MG, but because it has many potentially serious side effects, it’s often reserved for Weakness and fatigue are common in the use only when other drugs fail. general population, but the degree and pat- tern of these symptoms — particularly dip- Thymectomy lopia, ptosis and other signs of weakness Thymectomy — surgical removal of the in the eye muscles (see page 5) — should Plasmapheresis was developed by thymus (see page 5) — is recommended alert a neurologist to the possibility of MG. MDA scientists in the late 1970s to for thymoma and for most cases of gen- provide relief from MG. The process eralized MG. It’s believed to be the only The neurologist is likely to ask many ques- removes antibodies from the blood tions and to conduct a physical exam to and may have to be done repeatedly. therapy capable of producing long-term, drug-free remission from MG, but most determine the extent of weakness. To look data regarding its use have come from for evidence of increased weakness fol- case studies rather than clinical trials. lowing exertion, he or she might ask the patient to look up without blinking for one Thymectomy is estimated to produce or two minutes, hold the arms out for as remission from MG in about 30 percent long as possible or climb up steps. of people. It’s also known to increase strength or reduce the need for medica- If the physical exam is consistent with MG, Weakness in eye muscles alerts tion in an additional 50 percent. These the neurologist usually orders a blood test neurologists to the possibility of MG. improvements may take several months designed to detect antibodies to the ACh to several years after surgery to occur. receptor. (A blood test for MuSK antibodies also should be available soon.) A positive Thymectomy usually has the most favor- test result confirms a diagnosis of MG. able outcomes in people who are under age 60 and early in the course of the dis- If the blood tests are negative, the next ease. Because the thymus is required for step is usually electrodiagnostic testing, immune system development, most doc- in which electrodes are used to measure tors prefer not to perform the surgery on the electrical signals in muscle. Surface prepubescent children. electrodes (similar to those used in elec- trocardiograms) deliver small shocks to a Plasmapheresis and intravenous nerve in the arm, leg or face, while other immunoglobulin (IVIG) surface electrodes record the responses In plasmapheresis, also known as plasma in muscle. In MG, a muscle’s response exchange, an intravenous line is used to to repeated nerve stimulation declines remove antibodies from the blood. IVIg rapidly. therapy is essentially an injection of non-

8 MG • ©2011 MDA In addition to or in place of electrodiag- nosis, the neurologist might try giving an intravenous injection of (Tensilon), a fast-acting . A temporary increase in strength after this “Tensilon test” is consistent with either MG or CMS.

If a diagnosis of MG is confirmed, a CT scan, chest X-rays or magnetic resonance imaging (MRI) will be used to examine the thymus and look for evidence of thy- moma.

Additional tests may be used to probe for LEMS or CMS (see pages 10 and 11).

9 MG • ©2011 MDA Lambert-Eaton Myasthenic Syndrome (LEMS) What is LEMS? (involuntary) symptoms such as dry mouth, constipation, impotence and blad- ambert-Eaton myasthenic syndrome der urgency. L(LEMS) is a rare autoimmune disease whose symptoms and origins are some- LEMS with cancer has its onset in adulthood, what similar to those of MG. While MG but LEMS without cancer may affect children. targets the ACh receptors on muscle cells, LEMS interferes with ACh release from How is LEMS treated? nerve cells. Long-term treatment and prognosis of Some 85 percent to 90 percent of people LEMS depend on whether it occurs with with LEMS test positive for antibodies or without cancer. Although cancer is against the P/Q type voltage-gated calcium life-threatening, it can be treated with channel (VGCC). This protein is a pore radiation, surgery or chemotherapy. When that allows calcium entry into nerve cells, these treatments are successful and the which is required for ACh release. cancer goes into remission, LEMS usually goes into complete or partial remission as In about 60 percent of cases, LEMS is well. associated with small-cell lung cancer (and more rarely with other types of Prior to cancer treatment, or in LEMS cancer), which might be diagnosed at patients without cancer, immunosuppres- the same time as LEMS or years later. sant drugs, IVIg and/or plasmapheresis There’s evidence that the cancerous cells (see page 8) are often helpful. inappropriately make VGCC, triggering Symptomatic relief can be achieved with the immune system to make anti-VGCC LEMS symptoms usually begin with Mestinon and/or 3,4-diaminopyridine (3,4- leg weakness, often followed by weak- antibodies. The trigger for LEMS without DAP), a drug that prolongs the opening of ness in the muscles of the eyes, face cancer is unknown. and throat. Sometimes the weakness VGCC in nerve endings and thus enhances temporarily improves after exertion. ACh release. This drug may be hard to What are the symptoms of obtain as it’s only formulated by a few LEMS? pharmacies in the United States. The first symptoms are usually leg weak- ness and difficulty walking. Oculobulbar How is LEMS diagnosed? weakness (affecting the muscles of the The autonomic symptoms and predomi- eyes, face and throat) may occur later, nant leg weakness of LEMS help to dis- causing ptosis (see page 5), speech tinguish it from MG. Electrodiagnostic impairment and swallowing problems. testing that shows an increased muscle Unlike weakness in MG, weakness in response to repeated stimulation also LEMS temporarily improves after exer- favors LEMS rather than MG (in which tion. (It’s thought that, with repeated the response decreases). In most cases, activity, calcium gradually builds up in the LEMS can be confirmed by detection of nerve cells, increasing the amount of ACh anti-VGCC antibodies in the blood. released.)

Julie Long is an artist who has Because ACh regulates many bodily func- LEMS. tions, LEMS sometimes causes autonomic

10 MG • ©2011 MDA Congenital Myasthenic Syndromes (CMS) What is CMS? Drug treatment: cholinesterase inhibitors ike MG, CMS produces weakness Land fatigue caused by problems at Postsynaptic CMS the neuromuscular junction (see page (ACh receptor deficiency, 3). But while MG is autoimmune, CMS fast-channel CMS) is an inherited disease caused by defec- Cause: tive genes. Genes are recipes for mak- ACh receptors are missing or don’t stay ing proteins, and the genes defective in open long enough. CMS are required for making the ACh Symptoms: receptor or other components of the Vary from mild to severe. In infants, neuromuscular junction. may cause severe weakness, feeding There are many types of CMS, grouped and respiratory problems, and delayed into three main categories named for motor milestones (sitting, crawling and the part of the neuromuscular junction walking). Childhood and adult-onset Nerve cell ending that’s affected: presynaptic (the nerve cases often cause ptosis and fatigue, cell), postsynaptic (the muscle cell) or but usually don’t interfere with daily liv- synaptic (the space in between). ing. A Symptoms and treatment options vary Drug treatment: depending on the type of CMS. The cholinesterase inhibitors and 3,4-DAP C cholinesterase inhibitors used to treat (see page 7) MG are helpful in some types of CMS, but may be harmful in others. It’s impor- Postsynaptic CMS B (slow-channel CMS) Muscle cell tant to realize that since CMS isn’t an autoimmune disease, it doesn’t respond Cause: to immunosuppressant drugs or other ACh receptors stay open too long. CMS results from genetic flaws at the neu- romuscular junction — where the nerve treatments aimed at the immune system. Symptoms: cell meets the muscle cell. The type of CMS depends on where the defective gene lies: (A) As its name implies, CMS usually has Infant-onset cases cause severe weak- in the nerve cell — presynaptic CMS; (B) the a congenital (at or near birth) onset, ness, often leading to loss of mobility muscle cell — postsynaptic CMS; or (C) the and respiratory problems in adoles- space in between — synaptic CMS. but it can manifest in children and even in adults. Later-onset cases tend to be cence. Adult-onset cases may not be less severe. disabling. What are the types of CMS and Drug treatment: how are they treated? or fluoxetine (both plug the ACh receptor) Presynaptic CMS Cause: Synaptic CMS Insufficient release of ACh Cause: acetylcholinesterase deficiency Symptoms: Commonly manifests as CMS with epi- sodic apnea (CMS-EA), which has its onset in infancy and causes oculobulbar weakness and episodes of apnea — a temporary cessation of breathing.

11 MG • ©2011 MDA Symptoms: Severe weakness with feeding and respira- tory difficulties from birth or early child- hood. Weakness also causes delayed motor milestones, and often leads to reduced mobility and scoliosis (curvature of the spine).

Drug treatment: none How is CMS inherited? With the exception of slow-channel CMS, the inheritance pattern for the types of CMS described here is autosomal reces- sive. This means that it takes two copies of the defective gene — one from each parent — to cause the disease. Slow- channel CMS is inherited in an autosomal dominant manner. This means that one copy of a defective ACh receptor gene is enough to cause the disease, so an affected parent has a 50 percent chance of passing the disease on to a child. How is CMS diagnosed? A negative test for ACh receptor antibod- ies in the serum (blood) can help dis- tinguish CMS from MG, but doesn’t rule out seronegative MG. A family history of myasthenic symptoms supports the CMS diagnosis, but isn’t necessary. Genetic testing and physiological tests on biopsied muscle tissue, done on a research basis, may be needed to define some types of CMS.

Unlike MG, CMS isn’t an autoimmune disease. The earlier the symptoms appear, the more severe the disease is likely to be.

12 MG • ©2011 MDA MDA’s Search for Treatments and Cures he MDA website is constantly updated an eye to improving these activities. At Twith the latest information about the the same time, several other MDA-backed neuromuscular diseases in its program. groups are studying safer and more See the latest research news at www.mda. effective ways to target the malfunction- org. ing parts of the immune system while preserving the beneficial activities of this MDA’s commitment to research on myas- system. thenia gravis began many years ago, when little was known about the cause of MG In the past, people with CMS were often and its mortality rate was high. told they had MG and were subjected to years of pointless immunosuppressive In the early 1970s, MDA-funded research- therapy. ers helped establish the autoimmune nature of MG. They showed that people By identifying the genetic defects that with the disease have a reduced number cause CMS, MDA-funded scientists have of ACh receptors and that antibodies to improved the diagnosis of CMS and dis- the receptors can induce MG in laboratory covered drugs that are effective against it. animals. They’re pursuing better drug treatments, and eyeing techniques to fix or replace These discoveries led swiftly to the lifesav- the underlying genetic defects by gene ing use of immunosuppressant drugs to therapy. treat the disease.

MDA scientists began using some of the same drugs for LEMS in the 1980s, when they helped link the disease to an autoim- mune attack against the calcium channels in nerve endings.

They also began treating LEMS with the drug 3,4-DAP (which increases calcium channel activation) and continue to study calcium channels with an eye toward improved drugs. MDA-funded researchers also developed plasmapheresis specifically for treating MG and LEMS.

MDA clinics have been sites for clinical trials to evaluate new immunosuppres- sant medications, such as mycophenylate mofetil (CellCept) and etanercept (Enbrel), as well as the role of thymectomy, in MG treatment.

As of late 2009, several MDA-supported researchers are continuing to study the mechanisms by which signals are trans- mitted by nerve cells and received by muscle fibers in health and disease, with

13 MG • ©2011 MDA MDA Is Here to Help You he Muscular Dystrophy Association Everyone registered with MDA automati- Toffers a vast array of services to help cally receives Quest, MDA’s award-win- you and your family deal with myasthenia ning quarterly magazine. Quest publishes gravis or myasthenic syndromes. The staff detailed articles about research findings, at your local MDA office is there to assist medical and day-to-day care, helpful you in many ways. The Association’s ser- products and devices, social and family vices include: issues, and much more. Other MDA pub- lications can be found at www.mda.org/ • nationwide network of clinics staffed by publications; many booklets are available top specialists in Spanish. Ask your local office for “MDA • MDA summer camps for kids with neu- Services for the Individual, Family and romuscular diseases Community” and for help with obtaining copies of other publications. • help with locating durable medical equipment through its national equip- If you have any questions about myas- ment program thenia gravis or myasthenic syndromes, someone at MDA will help you find the • financial assistance with repairs or answer. To reach your local MDA office, modifications to all types of durable call (800) 572-1717. medical equipment

• annual occupational, physical, respira- tory or speech therapy consultations

• annual flu shots On the cover: Terra is an attorney. She’d had symp- • support groups for those affected, toms of muscle weakness since child- spouses, parents or other caregivers hood and got a correct diagnosis of congenital myasthenic syndrome in • online support services through the 2000. Her symptoms are stabilized with medication. e-community myMDA and through myMuscleTeam, a program that helps recruit and coordinate in- home help

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14 MG • ©2011 MDA MDA’s Purpose and Programs he Muscular Dystrophy Association Metabolic Diseases of Muscle Tfights neuromuscular diseases through Phosphorylase deficiency (McArdle disease) an unparalleled worldwide research effort. Acid maltase deficiency (Pompe disease) The following diseases are included in Phosphofructokinase deficiency MDA’s program: (Tarui disease) Debrancher enzyme deficiency Muscular Dystrophies (Cori or Forbes disease) (Steinert disease) Mitochondrial Duchenne muscular dystrophy Carnitine deficiency Becker muscular dystrophy Carnitine palmityl transferase deficiency Limb-girdle muscular dystrophy Phosphoglycerate kinase deficiency Facioscapulohumeral muscular dystrophy Phosphoglycerate mutase deficiency Congenital muscular dystrophy Lactate dehydrogenase deficiency Oculopharyngeal muscular dystrophy Myoadenylate deaminase deficiency Distal muscular dystrophy Emery-Dreifuss muscular dystrophy Due to Endocrine Abnormalities Motor Diseases Hyperthyroid myopathy Amyotrophic lateral sclerosis (ALS) Hypothyroid myopathy Infantile progressive spinal muscular atrophy Other Myopathies (Type 1, Werdnig-Hoffmann disease) congenita Intermediate spinal muscular atrophy (Type 2) Juvenile spinal muscular atrophy (Type 3, Kugelberg-Welander disease) Myotubular myopathy Adult spinal muscular atrophy (Type 4) Spinal-bulbar muscular atrophy (Kennedy disease) Inflammatory Myopathies Polymyositis MDA’s website, mda.org, is Dermatomyositis constantly updated with the latest Inclusion-body myositis research news and information Diseases of Neuromuscular about the diseases in its program. Junction Follow MDA on Facebook, Twitter Myasthenia gravis and YouTube. Lambert-Eaton (myasthenic) syndrome Congenital myasthenic syndromes Diseases of Peripheral Nerve mda.org • (800) 572-1717 Charcot-Marie-Tooth disease Friedreich’s ataxia Dejerine-Sottas disease ©2009, 2011, Muscular Dystrophy Association Inc.

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15 MG • ©2011 MDA