Congenital Myasthenia and Myopathy: Cameron's Journey

It's been almost a year since my last blog post.  A lot has happened during that time, including Cameron, our six year old son, starting and finishing Kindergarten.  He had a really good year, but he started to have seizures in the fall (I'll blog about those in a later post), and he started experiencing a greater amount of fatigue and worsening stability associated with movement.  Just to briefly recap, Cameron was diagnosed with a non-specific myopathy (muscle disease) when he was 3.5 years old. His neurologists wanted to do the muscle biopsy due to his history of delayed motor development, muscle weakness, and abnormal findings on an intramuscular EMG.  The doctor that conducted his biopsy was fairly certain that he had a congenital myopathy, but the biopsy came back as non-specific.  Cameron has been receiving weekly occupational and physical therapy services since he was three years old.  He has been making steady progress, thanks to the wonderful therapists at Kids Therapy Spot here in Starkville and at Sudduth Elementary, but he is still about a year or two behind where he should be in terms of his gross and fine motor skills.  That brings us to this summer (a more detailed list of Cameron's journey can be found towards the end of this post).

We saw Cameron's pediatric neurologist, Dr. Parker (UMMC), in May, and expressed our concerns about his fatigue and how his stability and gait had gotten worse.  She ran some blood tests to check for possible metabolic disorders, and scheduled Cameron for another Brain MRI.  All his blood work came back negative.  His MRI did show some areas of the brain that lacked myelination (this also showed up on his first brain MRI when he was four), but both Dr. Parker and another neurologist told us this shouldn't be affecting his motor planning and movements because it is not located in the motor centers of the brain.  So, that did not explain his worsening fatigue and stability (sometimes Cameron likes to say his legs feel wobbly).  When we were in the hospital last week for his video EEG, Dr. Davis, the doctor who did Cameron's muscle biopsy, stopped by to check on him.  We told him how Cameron was doing and that his fatigue and stability seemed to be getting worse.  He asked us a lot of questions about Cameron related to his movements.  He came back a few hours later and said he wanted to do a nerve conduction test to look for congenital myasthenia.  Two of the main symptoms of congenital myasthenia are fatigue and muscle weakness.  The only drawback to this test is that it has to be done under anesthesia.  Dr. Davis would stimulate several peripheral nerves at a high frequency and for a long duration and look at how this affected the muscular response using EMG.  Abnormal responses would indicate a likelihood for congenital myasthenia.  We decided to go ahead and let Dr. Davis perform this test on Cameron, which he did yesterday morning (Dr. Davis went above and beyond to get this test scheduled so quickly, and while we were already in Jackson for doctors appointments.  We can't thank him enough for that).

After conducting the test, Dr. Davis told us the results were inconclusive.  Some of his more distal nerves, like the peroneal, ulnar, and median nerves displayed a normal response, but he did see an abnormal response when he stimulated Cameron's musculocutaneous nerve and measured the response of his biceps brachii (essentially, the amplitude of the response of this biceps brachii decreased more than normal after being stimulated repetitively).  Based on Cameron's symptoms and this abnormal response in a more proximal nerve (myasthenia generally affects the proximal nerves and muscles more than the distal ones), he wants to proceed forward as if Cameron has this condition. Since there are different types of congenital myasthenia, we will be referred to genetics so they can test for a few specific types.  Dr. Davis said it is very important to know what type of congenital myasthenia a patient has before you put them on medication, because the medication for certain types of myasthenia can have negative effects on other types of myasthenia.  The other treatment for myasthenia is therapy, which he is already getting.

So, what is congenital myasthenia?  It is a disease of the neuromuscular junction.  The neuromuscular junction is the place where the motor neuron communicates with the muscle that it innervates.  There are three parts to the neuromuscular junction.  The presynaptic membrane (the end of the axon, which is the part of the motor neuron that takes the signal to the muscle), the synapse, which is the small space between the axon and the muscle, and the motor end plate, which is the specialized portion of the muscle fiber that receives the signal from the axon.  When you want to move, your brain sends action potentials (signals) down your motor neurons to the muscles that are required to perform the task.  At the neuromuscular junction, vesicles that contain the neurotransmitter acetylcholine are released from the end of the axon, and the acetylcholine diffuses across the synaptic cleft and binds to acetylcholine receptors found on the muscle.  This process will eventually lead to a muscle contraction, force development, and movement.  When you move, this process happens many times in the neuromuscular junctions that are involved in the movement.  

There are two types of myasthenia, myasthenia gravis, which is more common, and congenital myasthenia.  Both types of myasthenia disrupt the communication between the motor neuron and muscle at the neuromuscular junction. Myasthenia gravis is more common.  It is an auto-immune disorder in which the body attacks the acetylcholine receptors that are located on the muscle (motor end plate).  Since there are fewer receptors for acetylcholine to bind with, less force is produced, leading to muscle weakness.  Congenital myasthenia can effect all three parts of the neuromuscular junction.  Based on the results of Cameron's nerve conduction test, Dr. Davis believes that he has a problem on the post synaptic membrane.  There are basically two types of post synaptic congenital myasthenia: in one type, the acetylcholine channels do not stay open long enough (fast channel CMS), and in the other type they stay open too long (slow channel).   There are genetic tests that can be conducted to determine which type he has, and then medication can be prescribed to help with the symptoms. There is no cure for congenital myasthenia, and Cameron would still attend therapy sessions to address his muscle weakness, but the medication could help with the fatigue and weakness.

So, what does this mean in terms of Cameron's movements and his quality of life?  Since both the myasthenia and myopathy are congenital disorders/diseases, Cameron has had them his whole life. He is able to walk, run, jump, write, and do other basic motor skills, but they are just more challenging for him due to the muscle weakness and fatigue.  As a six year old, most of his motor skills are performed at the level of a four year old.  His myasthenia/myopathy causes him to be extremely sensitive to the heat, which is challenging in the south.  When he has a day where he exerts a lot of energy playing, swimming, etc., he is extremely fatigued the next day and his movements are even more uncoordinated.  The fatigue is different from a "tired" fatigue, his muscles just do not function as well after he has exerted a lot of energy.  He is a very happy, kind, and loving six year old, and cognitively he is very smart.  At the end of kindergarten in May his teacher told us he was reading on a second grade level.  Motor movements are just more challenging for him, but with the help of physical and occupational therapy he has come a long way, and if the doctors can identify the specific type of congenital myasthenia he has, hopefully medication can help some as well.  It's been a tough journey for us the past few years watching him struggle and undergo so many different neurological tests and procedures, but we know he is a special boy that has already touched many different lives. We definitely have our concerns and worries about the future but we know he can overcome these challenges.

I'll post an update as we proceed forward with this, and I'll also post about his seizures and our experience with them.

Here is a timeline of events as they relate to Cameron's journey:

March 2014: Referred to Kids Therapy Sport for an evaluation by physical/occupational therapists due to concerns about his motor development.  Both therapists that evaluated him noted that he was very behind on his motor development/skills, he tested at a 15-18 month level for some gross motor skills (he was 36 months old).  He began weekly therapy sessions (both PT and OT) and was referred to a pediatric neurologist at UMMC (University of Mississippi Medical Center).

October 2014: Cameron's was evaluated by Dr. Parker at UMMC (she's very popular and has a lot of patients), she diagnosed him with hypotonia (low muscle tone) and scheduled him for an intramuscular EMG.

Novemeber 2014: Dr. Davis, a neurologist that specializes in diseases of the neuromuscular system, conducts an intramuscular EMG and it is abnormal.  He tells us that Cameron likely has a myopathy (muscle disease) and schedules a muscle biopsy.

December 2014: Dr. Davis performs the muscle biopsy, taking a piece of Cameron's left quadriceps (under anesthesia).  While Dr. Davis originally thought Cameron had a type of congenital myopathy, the biopsy comes back as a non-specific myopathy.

December 2015: Cameron has a brain MRI.  The results show some areas of his brain that haven't completely myelinated, but Dr. Parker says that at his age, these areas could eventually myelinate. She wants to do a follow up MRI in one to two years.

November 2016: Cameron begins to start having seizures (more on this later).  He is started on seizure medicines and has an outpatient EEG.

February 2017: Cameron begins limping and favoring his left leg.  His physical therapist refers him to Columbus Orthopaedic for an evaluation since we are most concerned about his left hip.  X-rays of his hip look normal, but we are referred to pediatric orthopedics at UMMC.  We see Dr. Schrader about a month later and he also tells us that his hip x-ray looks normal.  He believes Cameron is limping due to his muscle weakness and increased laxity (motion) in his left hip.  Although Cameron's gait is still abnormal he is no longer favoring his left hip.  We had a follow up appointment with Dr. Schrader this past week and he is still pleased with Cameron from an orthopedic perspective.  We are glad to have an pediatric orthopedist on Cameron's medical team.

May 2017:  At an appointment with Dr. Parker, we tell her how his fatigue, balance, and coordination have gotten worse (as noted by us, his therapists, and his teachers).  She is concerned.  She orders some bloodwork to check for possible metabolic disorders (they took about 12 vials of blood) and some other genetic conditions.  These tests come back negative.  She also refers him to a pediatric cardiologist since he has a muscle disease.  He has an EKG and echo-cardiogram and these both come back normal.  He will likely have to have a yearly cardiology appointment (EKG and echo) for the rest of his life.

June 2017: Cameron has a second brain MRI under anesthesia.  It shows the same areas lack myelination as the first MRI, but thankfully these are not any of the motor areas of the brain (primary motor area, premotor area, cerebellum, basal ganglia, and thalamus).

July 2017: Cameron has a three day video EEG in the hospital where he has electrodes attached to his head and cannot leave his room.  Dr. Davis schedules the nerve conduction test for the next week.

August 2017:  Dr. Davis performs the nerve conduction tests with the abnormal finding in the musculocutaneous nerve, indicating there is a good chance he has congenital myasthenia.  Dr. Davis is going to consult with Dr. Parker, but the next step is likely genetic testing to identify the specific type of congenital myasthenia.