Friday, August 11, 2017

Seizures and Cameron

I mentioned in my last blog post that Cameron had started having seizures back in the Fall of 2016. This post will discuss seizures and what we have experienced regarding Cameron's seizures.

·        A seizure is temporary disruption of brain function resulting from abnormal, excessive neuronal activity.  Neurons are the cells that make up your brain.  There are over a billion neurons in your brain that are constantly communicating with each other.  A person that has repeated seizures is diagnosed with epilepsy.  Cameron's neurologist, Dr. Parker, said that any person that has multiple seizures has epilepsy, but she does not really like to use the term because many times people think of a person with epilepsy as having many frequent, uncontrolled seizures, and often times this is not the case.  One interesting thing we learned is that approximately 3% of the population (United States) living to the age of 80 years are diagnosed with epilepsy.  Not all seizures are the same, and seizures can results in different noticeable signs.  These are called positive and negative signs.

o   Positive signs: perception of a flashing light or jerking of an arm
o   Negative signs: impairment of consciousness and self-awareness, transient blindness, paralysis

·         The signs and symptoms of a seizure depend on the location and extent of the brain regions that are affected.  There are two main types of seizures: Focal, or partial seizures (sometimes called complex partial seizures), and generalized seizures.  Below are the differences between the two.
·         Focal (partial) Seizures
o   Originate in a small group of neurons, symptoms depend on the location of the focus within the brain
o   Might include jerking with the right hand and progress to clonic movements (jerks) of the entire right arm
o   Patient may or may not lose consciousness
o   Onset is often preceded by symptoms called auras
o   Auras include a sense of fear, rising feeling in the abdomen, or even a specific odor, and represents the earliest onset of a seizure
o   The time after a seizure until a patient returns to his or her normal level of neurological function is called the postictal period
·         Generalized Seizures
o   Begin without an aura and involve both hemispheres
o   Can be further divided into convulsive and nonconvulsive types
o   Most common type of nonconvulsive generalized seizure in children is the typical absence seizure
§  Normally last less than 10 seconds, associated with a cessation of all motor activity, and results in a loss of consciousness but not posture

§  Patient may appear to be in a trance 

We first noticed Cameron having what we originally called "spells" back in the Fall of 2016.  He would get really quiet and then have a distant stare on his face for about 30 seconds.  Afterwards, he would be highly emotional or agitated, and them complain of being tired (this was the postictal period).  Cameron has never had jerking or convulsions with his seizures.  It is a common misconception that all seizures involve some form of jerking or convulsions, which they do not.  I think that is due to the way seizures are depicted on TV and in the movies.  At first we were not sure what was going on, but after talking with his Kindergarten teacher, we thought he might be having seizures.  We called his neurologist and they immediately started him on seizure medication and scheduled him for an EEG. Neurologists can use EEG (electroencephalography) to look at brain activity and detect abnormal activity that is associated with a seizure.

Cameron had his first EEG at UMMC in November of 2016.  It only lasted 30 minutes and did not show any abnormal activity.  His neurologist told us that did not mean he was not having seizures, he just did not have any during that 30 minute time period, which was good.  She believed that he was having seizures (focal seizures), and wanted to keep him on his seizure medication.  She also wanted to schedule him for a video EEG.  This would require a 3 day hospital stay where he was constantly monitored using EEG and video cameras.  Over the next few months, we would notice Cameron having one or two seizures a month.  We saw the same signs, and he would be really tired the next few days after a seizure.  His neurologist changed the type and amount of his seizure medication until we found a stable combination.  Since he was still having seizures, he had the video EEG conducted at Blair Batson Children's hospital this past July.  It was a very tough time for him, as you can see in the picture above, he had to wear the EEG electrodes on his head for 3 days and could not leave the hospital room.  They also had to put an IV line in his hand just in case he had a seizure and they needed to give him emergency medicine quickly.  While he was in the hospital, they gradually stopped his seizure medication.  He did not have any of the focal seizures we had been seeing, but they thought he might have been having seizures in his frontal lobe, which are very difficult to diagnose.  Dr. Parker told us the data was not conclusive, and even if he was having frontal lobe seizures, she probably wouldn't change his medicine.  She told us again that just because he did not have any seizures in the hospital did not mean that he wasn't having them, but that he wasn't having them frequently.  He is on two different seizure medications right now, she wants to gradually decrease one of the medicines and increase the other so that he only has to take one of them.  He currently has to take two different medications twice a day.

Sunday, August 6, 2017

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.

Friday, August 19, 2016

Kinesiology and the 2016 Olympics: Part VI Race walking

Today we have a guest blogger,  my doctoral student, Jeffrey Simpson.  Jeff is a second year student in our department working towards his PhD in biomechanics, and he is a big fan of race walking. Check out his thoughts below, and check you can check out Jeff's race walking form by clicking on this link.

This morning while I was eating breakfast and drinking my daily cup (or two) of coffee, I received a text message from Dr. Knight telling me that Olympic race walking was on NBC Sports. Since I arrived at Mississippi State in the Fall 2015 to work on my PhD in biomechanics under Dr. Knight, my lab mate and colleague, Brandon Miller (other PhD student in biomechanics), and I are always talking about race walking and discussing how competitive the sport has become. If you’ve never heard of race walking, I promise that you’re missing out.

In the 2016 Rio Olympics there are both men’s and women’s 20 and 50 km races. Believe it or not, these race walking athletes are able to “walk” 20/50 km faster than the majority individuals can run a 20/50 km. So how do we classify someone who is walking or running? The two main phases during the gait cycle we examine are the stance phase (when the foot is in contact with the ground) and the swing phase (when the leg moves forward). The phase we focus on when determining if someone is walking is the stance phase, which has two periods. The double limb stance period (when both feet are in contact with the ground) and the single limb stance period (only one foot in contact with the ground). However, if neither feet are in contact with the ground at any given moment this would be considered the flight phase (period of no support), which indicates running. This is how the IAAF enforces the rules and regulations of race walking, which states that the athlete must have no visible loss of contact with the ground (one foot must always be in contact with the ground) and the knee must be extended from the moment of initial contact (when the foot strikes the ground) until the athlete reaches the upright position. Throughout the race (20 or 50 km), officials constantly monitor athletes and issue red cards if the previously mentioned rules are broken. If an athlete receives 3 red cards, they are then disqualified from the race.

From a biomechanics perspective, we are able to analyze the gait kinematics and determine the individuals walking speed. As with running, the two main factors that determine speed are stride length and stride frequency (also referred to as cadence). In order for a race walker to optimize their stride length/frequency, they must exaggerate their gait by excessive pelvic rotations (shifting their hips left and right) and shoulder movements to oppose the pelvic rotations. Additionally, athletes will decrease the time their foot is in contact with the ground (ground contact time).  They also position their support leg close to their midline so that their center of mass passes directly over the support foot in order to maintain walking speed by decreasing breaking forces, which helps maintain movement efficiency. Although we might view this event as a joke, or even think it is funny, it is quite amazing what these athletes are able to accomplish. Race walking is actually a difficult task, if you try to “race walk” you’ll quickly find out that it’s hard to maximize your stride length/frequency without running. Provided in the link is a YouTube video of elite race walkers from the 2012 Olympic Games in London. Watch how quickly they are able to move while still being able to maintain walking gait.

Tuesday, August 16, 2016

Kinesiology and the 2016 Olympics Part V: Appreciating Usain Bolt

Usain Bolt made history on Sunday night, becoming the first athlete to win the men's 100 m race at three different Olympics (2008, 2012, 2016).  There have been very few to win the 100 m race at back to back Olympics, so for Bolt to do it at back to back to back is very impressive.  He is definitely the best sprinter of all time and this accomplishment may never be matched.

From a biomechanics perspective, there are several factors that enable Bolt to run at such a high velocity.  At six feet, five inches tall, he has very long legs, which enables him to cover more ground with each step and stride than his competitors.  However, being tall and having long legs does not automatically mean you will be a fast runner. Take Shaquille O'Neal for example.  What Bolt is able to do that most people with long legs cannot do is to have a very high step and stride frequency, meaning he can apply a force very quickly to the ground, pick his foot off the ground, and swing his leg through and get it back on the ground in a very short amount of time. We can measure how hard it is to rotate something by an object's moment of inertia, which is the product of the mass of the object and how the mass is distributed about the axis of rotation (radius of gyration, which is a squared value).  For Bolt, he has very muscular and long legs, which increases their mass. The length of his legs also moves the mass further away from the axis of rotation (the hip).  So, Bolt has a greater moment of inertia when swinging his legs while running than his opponents.  Imagine swinging a baseball or softball bat.  As the bat gets more massive (heavier) and longer, it becomes more difficult to swing the bat. The fact the Bolt can overcome this larger moment of inertia and still achieve a very high step and stride frequency really sets him apart from all the other sprinters.

Bolt is also a very powerful runner.  He is able to apply a larger amount of force to the ground in a shorter amount of time than his opponents, thus giving him a greater amount of impulse and a greater change in momentum.  This interactive piece from the New York Times offers a really good analysis of Sunday's race.   Although Bolt has a poor reaction time (0.155 s on Sunday, which was the second worst in the field), he is able to make up for that with his stride length, stride frequency, and his superior ability to apply more force to the ground in less time than his opponents.

Here is another piece from the New York Times that shows how Bolt stacks up against all previous medalists in the 100 m race.  It's a very interesting look at the history of the race.  Bolt still has the 200 m race to run, it will be very interesting to see if he can also win that one again.

Saturday, August 13, 2016

Kinesiology and the 2016 Olympics Part IV: False Starts and Reaction Time

With the Olympics shifting away from the pool and towards the track, you might notice that a race starts but they stop it immediately, call all the runners back, and make them start again.  Also, the runner that started early is disqualified from the race. Sometimes, it is obvious that a runner starts before all the others and is disqualified.  Other times, it may be tough to tell that a runner started too soon.  So, how do they know that a runner "anticipated" the starting gun and started too soon? 

The starting blocks the athletes use have sensors in them that detect the amount and timing of the force applied to them by the runners' feet.  If the force applied to the blocks exceeds a certain threshold (I haven't been able to locate what this threshold is) in less than 0.1 (100 ms) seconds after the gun is fired, the runner is called for a false start and disqualified from the race.  This happened here to Usain Bolt in at the 2011 World Championships.  Why is this rule in place and why was 0.1 seconds chosen?

The purpose of the rule is to prevent the athlete from anticipating the firing of the starting gun and gaining an advantage on their opponents.  Most humans can react voluntarily to a stimulus (auditory, visual, etc) in about 120-150 ms.  Now, well trained athletes can react quicker than this because of their training, and there have been calls to lower the threshold to 90 ms (0.09 seconds).  Why does it take these athletes anywhere from 100-150 ms to start the race after the hear the firing of the gun? The answer lies in the nervous system and muscular system.

When responding to an auditory stimulus, the signal has to travel from the ears through sensory neurons to the brain.  Since this is a simple reaction time scenario (only one stimulus and one response), the brain can quickly process this signal and activate the alpha motoneurons that control the muscles in the legs, but it will still take some time for these signals to get from the brain down the motoneurons and to the muscles.  The time it takes from when the gun is fired to when the signal reaches the appropriate muscles is called the pre-motor time.  Once the signal reaches the muscle, it still takes time for chemical and mechanical process to occur within the muscle, force to be developed, and movement to occur.  This is known as the motor time.  Although it takes time for both of these processes to occur, it is remarkable to me the human body can respond so quickly.  However, if it occurs too quickly at the start of the race, the athlete will be disqualified.

Thursday, August 11, 2016

Kinesiology and the 2016 Olympics Part III: Propulsive Impulse

The last post discussed impulse (the product of the average amount of force and the time over which it is applied) when landing from a jump, and how it was important to increase the amount of time over which the force is applied when landing with a "soft" landing to decrease the injury risk.  When applying force, especially in a sport like volleyball, the force has to be applied to the ground when jumping or to the ball when attempting a spike over a short time period in order to be successful.

First, let's examine the vertical jump.  Volleyball players have to jump repeatedly over the course of a match.  If they are jumping to spike a ball or block their opponent's spike, they want to apply a large amount of force to the ground in a very short time period so they can reach the peak of their vertical jump as quickly as possible.  If two volleyball players, one on offense, and one on defense, both have the same vertical jump height, but one player can reach their peak height faster (in less amount of time) than the other, then that player will gain an advantage.  One way to reach the peak of their jump faster is by applying a large amount of force over a shorter time period than their opponent.  The more powerful the person is (power is the product of force and velocity, or how quickly someone can develop force), the more successful they will likely be.

Second, let's examine the volleyball spike.  When a player spikes a volleyball, their hand is in contact with the ball for a very short period of time.  They have to apply as much force as possible over a very small time period.  The same principle is true for other striking activities like hitting a baseball/softball, tennis ball, etc.   The more velocity the player can generate (the faster the can swing their arm), the greater the momentum they can transfer to the ball, which will result in a greater amount of impulse, because change in momentum is equal to the change in impulse (a post for another day).  The first graph on the bottom figure demonstrates how in the volleyball spike the propulsive impulse is generated by applying a large amount of force over a very short period of time.  The second part of the first graph relates to the last blog post regarding landing, which was applying a smaller amount of force over a longer period of time.  The second graph would relate more to a person jogging/running at a constant velocity.

Flannagan, S.P. (2014) Biomechanics: A case based approach (1st ed.), Jones & Bartlett.

Tuesday, August 9, 2016

Kinesiology and the 2016 Olympics Part II: Impulse when landing

During the first post on the Olympics I discussed how many different injuries can occur when an athlete lands from a jump.  Not only is the amount of force they have to absorb when landing a key factor, but the time over which that force is applied is also a very important factor.  Impulse is the product of the average amount of force and the time over which that force is applied.  In the graph below (Flannagan, S., 2014), the impulse for both the "stiff" landing and the "soft" landing are the same, but the amount of force that has to be absorbed by the jumper with a "stiff" landing is twice that of the force in the "soft" landing.  So, what is a "stiff" landing and what is a "soft" landing?  In a "stiff" landing, the joints of the lower extremity, primarily the hips, knees, and ankles, stay in a more extended position and do not give, or flex, as the person lands.  This means that the ground reaction force is applied over a very short time period.  In a "soft" landing, the person flexes their hips, knees, and ankles (technically dorsiflexion of the ankles) as they land to increase the amount of time over which the ground reaction force is applied.  This leads to a lower amount of stress placed on the lower extremity. That's why it is important to teach young athletes to perform a soft landing by flexing the joints of the lower extremity when they land (second figure below).

Flannagan, S.P. (2014) Biomechanics: A case based approach (1st ed.), Jones & Bartlett.