Monday, November 21, 2011

Myasthenia Gravis and Congenital Myasthenic Syndrome

Myasthenia Gravis (“grave muscle weakness”) is a condition where the neurotransmitters are unable to make the "jump" across the synapse between the neurons and the muscles.  The brain sends the messages but the muscles don't receive them properly.  This condition causes muscle weakness that worsens with continuous use and improves with rest.  Often muscles in the face are affected the most, so patients have trouble eating/swallowing and often have ptosis (droopy eye). I can also cause muscle weakness in the neck, torso, and limbs.  There are medications that treat myasthenia by helping to get the neurotransmitters to the muscles properly. 
There are two forms of myasthenia. The first and more common form is an autoimmune disease where the body produces antibodies that attack its own neurotransmitters.  This is what is commonly referred to as “MG”.  The onset for this autoimmune form usually occurs in women under 40 or men over 60.  Rarely, it can begin in childhood or adolescence but not usually in infancy. 
The second form of myasthenia is called Congenital Myasthenic Syndrome or “CMS.” In CMS the problem is not due to an autoimmune disease, as in MG, but a genetic defect. CMS is caused by a physiological problem at the connection between neurons and muscles. For one reason or another, the chemical signal from the nervous system to the muscle does not make it across the small gap between the neuron and muscle called the synapse, and as a result the muscle cannot carry out the commands coming from the brain. The chemical can fail to be produced or released in large enough quantities, or the muscle can fail to detect it properly. There are at least 10 different forms of CMS to date with new ones still being discovered. CMS is something that patients are born with and symptoms are usually present at birth or appear shortly after.  CMS is extremely rare (estimates range from 1 in 500,000 to 1 in 2 million). However, this is so under-diagnosed that it probably isn’t as rare as those estimates reflect. 

In both MG and CMS the symptoms can vary greatly from person to person.  Babies who are born with CMS will often present with very low muscle tone and be very lethargic. They can have feeding problems that range from difficulty breastfeeding, to requiring tube feeding.  They will be late with their gross motor milestones and can also have speech delays. They often have trouble clearing their secretions which can result in stridor breathing and sometimes necessitate a tracheostomy. Since the lungs are considered “voluntary” muscles, severe cases can cause respiratory problems that may require ventilator assistance.  Less severe cases that may go undiagnosed in infancy will later result in unusual fatigability, poor coordination, tendency to fall, and other neuromuscular symptoms. Over time, orthopedic issues can arise.  Ptosis, or “droopy eye” is one of the hallmark symptoms of CMS/MG, but is not always present.   MG has more of a gradual onset and is uncommon during childhood but not impossible.  In both cases, symptoms can “come and go”.  Heat and illness tend to exacerbate symptoms. 

Testing for the autoimmune form – MG – is much easier.  Blood tests can detect the antibodies that are attacking the neurotransmitters.  Another test, referred to as a Tensilon Test, is where a trial dose of the medication is administered to look for improvements in muscle tone.  If it is done later in the day when the patient is tired, their strength should improve and usually the most notable sign is that the eyes will no longer droop.
Testing for CMS is much more difficult. There will not be any antibodies present, so there is no blood test.  Often doctors will try EMG’s or muscle biopsies in these children to try and uncover the problem.  However, these results are not very reliable tests for CMS, especially in young children whose muscle fibers are very small.  So these tests can come back as “normal” even when there are serious problems of neuromuscular transmission. Many doctors are familiar with MG but not CMS and may associate a child’s symptoms with MG and therefore test the child for antibodies.  However, this test will come back negative in children with CMS leading the doctors to mistakenly “cross it off their list” of things to check for and move on.   All of this results in children going undiagnosed for months, even years.  It is usually recommended to do a trial of the medication and see if the baby improves.  Often that is the only definitive test for CMS.  Genetic testing can be performed at the Mayo Clinic, but routine genetic testing will not detect it.

Mestinon is the most common treatment for both MG and CMS.  It increases the amount of neurotransmitters.  Patients with autoimmune MG can also take immunosuppressant drugs, such as prednisone, to suppress the immune system.  Patients with CMS should not take these immunosuppressant drugs because they need to be able to fight off respiratory viruses which can be very dangerous for them.
Depending on which genetic defect is present in CMS, there may be additional drugs that can be used to correct the problem.  There are some very rare cases of CMS where Mestinon will actually worsen the symptoms, and there are other medications that those patients can take.  Many doctors are unaware of this.  So if a patient worsens with the medication, it COULD still be CMS just another form.  This is a VERY complex disorder.

                                                               Before Mestinon

                                                                   After Mestinon

The Mayo Clinic in Rochester, MN, is the center of excellence and research for CMS in the United States.  This is where the disorder was discovered.  This is the only place in the US that is able to conduct the genetic testing needed to identify the genetic nature of the disorder.  If you suspect your child has CMS, you should have your neurologist contact the Mayo Clinic for guidance.

The Myasthenia Gravis Foundation of America supports patients with MG.  There is not currently an organization devoted entirely to supporting CMS patients and their families.

Dedicated with love to my daughter, Ellen, and our new little buddy, Isaac!

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