Williams syndrome behavior profile- ADHD

Many people are familiar with the symptoms of attention deficit/hyperactivity disorder.  You envision a child who can't sit still nor concentrate on anything for very long.  In the Williams syndrome community, it is not unlikely to find many of the individuals diagnosed with ADHD.  Many individuals with WS have a very hard time paying attention to a task for a prolonged period of time.  In my own experience we noticed inattentive issues from a very early age of one.  Katie has trouble paying attention to a task during therapy for longer than only a few minutes, especially if it's a task that she doesn't enjoy.  We have since used strategies to help her remain focused, such as centering activities around highly motivating topics, using music, sometimes eliminating objects that are too interesting to the point she won't do anything else and reducing environmental distractions.  Considering she is only three, I foresee us needing to explore the ADHD topic in her future, but for now we use these strategies.  Many families find that help from a psychologist is necessary for their child to be successful at home and school.  This blog post is dedicated to them.

ADHD is tricky to treat...

In today's age, ADHD is so mainstream the acronym has become a term used in every day language.  Its diagnosis in children has increased so much over the past 10-20 years that many believe students today are over diagnosed.  With over diagnosis, many feel that kids are also over medicated. In the clinical world, however, psychologists see patients improving with the treatments and argue that ADHD is diagnosed more today than in the past because we are becoming more educated about the symptoms.  Parents and educators can identify kids who need help better now than in the past.  Psychologists don't see patients as unmotivated, lazy or free spirits.  They see them as a person with a brain that functions differently and one that can be treated when they work closely with a physician.  The increase in awareness has lead to more people receiving diagnoses and getting the treatment that they need to become more focused and successful.

ADHD is becoming more and more understood over time and as new research has answered baffling questions, the medical and psychological treatments offered have improved.  Despite the improvements, ADHD is a very frustrating condition for parents, doctors and educators to address because the basis of the condition is centered around brain chemistry which can be very complicated.  The variety of medications and the differences between how people's brains react to them can make treatment a long endeavor.  You often have to start with what works for most and modify it with different combinations of medications and/or change medication schedules. 

Another reason ADHD is so hard to treat is because it is often found paired with another disorder.   Those with ADHD also tend to display other psychiatric disorders such as anxiety, learning or behavioral disorders or mood disorders.  This rings true in WS, especially with anxiety, making the combinations of treatments very tricky to find the right balance.  When treating ADHD, the treatment has to mesh with all the psychiatric disorders and often symptoms of one will mask symptoms of another, complicating treatment.  This is why a child will often be put on one type of medication and will have to be carefully monitored to insure there aren't any adverse symptoms.

Research has also furthered our understanding of the variety of symptoms of ADHD.  It was once thought that ADHD was more prevalent in boys than in girls and the symptoms of hyperactivity.  Today we know that there are various forms of ADHD that affect both genders.  Research also indicates that 50% of children with ADHD don't actually grow out of it, the symptoms just change and the person often adapts.  The condition, though, will still affect them throughout life.  They have found that kids who are hyperactive and impulsive will shift as they age from the hyperactive classification towards a more inattentive classification.  Their outward behavior may change indicating that they have "grown out of ADHD" but in reality the inattentive state is easier to mask or is often misunderstood.  It is seen as a chosen behavior rather than a psychological disability.

Diagnosing ADHD

The classification system for ADHD has frequently changed in the past.  Today psychiatrists diagnose patients as Attention deficit-hyperactivity disorder followed by three types- inattentive type, hyperactive-impulsive type or a combination type. 

All of us have experienced periods of inattentiveness or hyperactivity throughout times in our lives. The difference between an energetic kid and one with ADHD is that they have to have 6 out of the 9 behaviors outlined as ADHD and it must interfere with their normal functioning at TWO aspects of life: at school, work, social settings and/or at home for a period of 6 months or more. Here is a list of the behaviors associated with this condition (from the National Resource center of ADIHD):

"Criteria for the three primary subtypes are: ADHD - Predominantly Inattentive Type

• Fails to give close attention to details or makes careless mistakes.
• Has difficulty sustaining attention.
• Does not appear to listen.
• Struggles to follow through on instructions.
• Has difficulty with organization.
• Avoids or dislikes tasks requiring sustained mental effort.
• Loses things.
• Is easily distracted.
• Is forgetful in daily activities.

ADHD - Predominantly Hyperactive/Impulsive Type

• Fidgets with hands or feet or squirms in chair.
• Has difficulty remaining seated.
• Runs about or climbs excessively.
• Difficulty engaging in activities quietly.
• Acts as if driven by a motor.
• Talks excessively.
• Blurts out answers before questions have been completed.
• Difficulty waiting or taking turns.
• Interrupts or intrudes upon others.

ADHD - Combined Type

• Individual meets both sets of inattention and hyperactive/impulsive criteria."

The science behind ADHD

There is still a lot to learn about the cause of ADHD. Scientists know that it has to do with the brain chemistry and neural connections. There is some evidence that certain environmental factors contribute to this condition but the current belief is that it is genetic and a child's environment can contribute to the severity of the symptoms (such as aggravating the condition due to food allergies or environmental toxins)

ADHD has been identified as a disorder of the brain's ability to coordinate its executive functions. In an average person, the brain has neural pathways that coordinate your working memory, your ability to organize a task and your use of internal language where you think through and "talk to yourself" in order to make sense and coordinate a task. All of these tasks are difficult for someone with ADHD because those neural pathways do not work as efficiently as they should.

Brown et al. explains this impairment of executive function as being synonymous to a type of leadership role. Think of a conductor of an orchestra who has to coordinate several types of musicians to play at the right time and tempo in order to produce beautiful harmony. Your brain works in much of the same way. You are receiving information from your environment and you need to choose what to act on, pull from memory on how to act on it, coordinate muscles and glands to produce the right combinations of actions, etc. It takes quite a bit of organization for your brain to maintain this task. This executive function of coordinating all the thoughts, memories, actions and interpreting the information your getting is coordinated by the executive function of the brain. The very place where ADHD has deficits.

Furthermore, as a person ages, they are called upon to use this executive function more and more. As a youngster, kids are hyper, they don't have big responsibilities and as they age they will be challenged more and more to use that executive function. This is why the inattentiveness becomes more apparent as a child ages. Often if a child doesn't have the hyperactive part of ADHD, they aren't even diagnosed as having inattentiveness until they reach middle-high school where they are called upon to take on more responsibility.

In addition to executive functions, those with ADHD have deficits in their working memory. Your working memory is a portion of your brain that takes information from the long term storage of memory and puts it into action. Basically its like opening a file cabinet of things you know and reading a folder you need to use at the moment. It is linked to acting on what you know, making connections between what you are learning to what you have learned and it is essential for understanding and initiating tasks. Deficits in this area will lead to students who don't finish tasks or have trouble starting them. 

There are emotional ties to those with ADHD as well. They often become hyper focused on something interesting and although they know they should be engaged in another activity and that if they don't it will cause them "trouble" down the road, they physically cannot find attention for the less interesting stimulus. This type of ADHD is often coupled with other psychological disorders such as mood disorders.

Research is unclear on the actual brain science that causes ADHD. Much of the early research has pointed to the neural pathways in the pre-frontal cortex (the portion of your brain behind your forehead). This area of the brain is what creates your personality, your ability to problem solve and think through academics. It essentially is the part of the brain that makes you, well, you. Later research indicates that, yes, this area of the brain is affected, but so are neural pathways or highways between memory in the thalamus, deep in the center of the brain and the parietal lobe where sensory information is processed in the top back of your brain. All these areas must coordinate efforts to produce a behavior and this is the essential workings of that executive function of the brain.

There is also evidence that brain chemistry has a lot to do with ADHD, particularly, dopamine. Dopamine is a neurotransmitter, a tiny chemical that is made by cells in the brain that allow one neuron to communicate with another. It is thought that ADHD has a deficit of dopamine and
catecholamines. There is a lot left to understand about this chemistry but it is widely known that medication that focuses on the increase of dopamine is effective in preventing inattentiveness in those with ADHD.


Treating ADHD in someone with WS is extra tricky...

More than 50% of individuals with Williams syndrome are diagnosed with ADD or ADHD. In studies, children with WS were compared to those with ADHD with comparable verbal abilities versus a control group of typical children. The children with WS were most like those diagnosed with ADHD and scored abnormally on the Conners ADHD rating scale. One Williams syndrome study showed that 43% of their study participants had ADHD and most of them were due to inattentiveness, not hyperactivity nor impulsiveness. 

There are only a handful of researchers who have studied ADHD and WS together.  This means that your WS child will most likely baffle a psychologist.  As mentioned before, ADHD as a whole is difficult to treat in anyone because most with ADHD have another condition in conjunction with it.  Most individuals with WS will have learning difficulties, anxiety, ADHD and their unique hyper-social personalities that will make identifying a treatment very difficult for most.

Most kids with WS don't meet every criteria of inattentiveness.  For example, a child with WS that is highly interested in something, such as a tv show, learning about their favorite item or are participating in highly motivating activities, such as music, will stay on task whereas the classic ADHD child will not be able to sit still regardless of the activity.  Also, kids with WS tend to become distracted by specific environmental triggers, such as noise, music, peer conversations, shiny objects and unexpected or novel items introduced to their environment.  Kids with WS tend to have selective attentiveness.  They have trouble maintaining their focus with external distractions that are interesting to them and as a result retain partial information.  Typically kids with ADHD will be inattentive for longer periods of time.  Other differences stem from the WS profile.  While kids with ADHD are often found to have trouble reading people socially, are less able to become empathetic with others.  WS is the exact opposite of this. 

In addition to a slightly different inattentive profile, individuals with WS display different behaviors than other children with ADHD inattentive type.  There are some researchers that argue against labeling WS with ADHD because kids with WS lack aggression that is oppositional to adults.  Kids with WS that act out are often due to anxiety or frustration due to their verbal ability rather than due to hyperactivity. This is just another example of how ADHD is not black and white as far as treatment goes. The combination of inattentiveness, anxiety and the WS behavior profile make diagnosing and treating ADHD very difficult for psychologists.

ADHD treatment for those with WS

There are only 3 studies as of date that studied the effectiveness of medications for ADHD in children with WS, making the treatment difficult for doctors and the families.  The studies also have small sample sizes so further studies are really needed before anyone should suggest one treatment over another.  Treating ADHD has always been very difficult and often require various trials from psychologists.  One study focused on the effectiveness to treat individuals with WS using methylphenidate (MPH), the medication found in Ritalin.  In the study, of 30 children treated, 60% of them improved (3 highly improved and another showed moderate improvement).  This improvement rate is the same as the effectiveness in the general population of ADHD children.  The main side effect was sadness, quiet, and withdrawn behaviors which was shown in 61% of the children taking MPH, so any children showing signs of depression should not be given this medication.  This side effect is much higher in those with WS than in individuals with ADHD alone (8%-22%).

To conclude:

So, in conclusion, there is a lot to learn about WS and the treatment of inattentiveness.  It is important for doctors and educators to work with the children.  Treatment will take time and will require parents to communicate effectively with psychologists so that the proper medications and timing is discovered for your child.  It is also important that schools include modifications and strategies for classroom teachers to use that will help your child maintain better focus in school.  Patience and open communication are essential for treating children with WS and ADHD.

Sources:

• http://www.ncbi.nlm.nih.gov/pubmed/20700845 Abstract of a study that shows the prevalence of ADHD in individuals with WS.
• http://jdc.jefferson.edu/cgi/viewcontent.cgi?article=1003&context=jeffjpsychiatry small psychiatric study that attempted to show that ADHD and anxiety in WS is due to the genetic deletion rather than family inheritance.
• http://books.google.com/books?id=9E9q5112WBgC&pg=PA286&lpg=PA286&dq=adhd+williams+syndrome&source=bl&ots=LdcJeiR7v0&sig=1iiN2afkh91X4siWCceAmkkXO-4&hl=en&sa=X&ei=0M_AT8-mDrKBsgLU9PTzCQ&ved=0CH0Q6AEwBA#v=onepage&q=adhd%20williams%20syndrome&f=false "Understanding williams syndrome behavioral patterns and interventions"
• http://onlinelibrary.wiley.com/doi/10.1002/ajmg.b.31247/full Study about the use of MPH treatments in individuals with WS.
• http://www.ncbi.nlm.nih.gov/pubmed/9203066 Second study about MPH and WS
• http://www.drthomasebrown.com/pdfs/comChapter.pdf A book that summarizes studies on ADHD and explains what trends in research say about the condition.

Visuo-spatial difficulties and how they cause motor delay

You're standing in a field, crouched in position for a fly ball.  Crack!  You hear bat against ball.  Your attention sharpens, your eyes focus on the movement in the air, you run to position your body in its path, hold out your glove, anchor your body to absorb the force, make adjustments in your stance and position as it approaches and you catch it.  All of these actions, although simple to most, are nearly impossible for someone with Williams syndrome.  As mentioned in other sections of this blog, those with Williams syndrome have low tone so their muscle strength and response is slow, but that is only part of the equation of motor delay.  Many of the brain studies that were discussed in the speech section of this blog focus on the spatial difficulties that are prominent in Williams syndrome (WS).  This section of the blog focuses on how this spatial disability inhibits movements in ways separate from low tone.

So, what does visuo-spatial mean?

Many individuals with WS have a hard time interpreting where they are in space.  They also struggle with directional orientation, such as understanding right from left and mirror images.  Visuo-spatial difficulties mean a person would have a hard time judging their surroundings, primarily with visual information, in order to understand where they are in their environment.  For example, imagine yourself navigating down a busy staircase.  It is crowded with people and you must walk in a cramped space.  Now make that stairway spiral and you must move with a swift motion to keep in pace with the crowd.  What do you do?  You may run your finger tips along the stair railing as you move.  You keep your eyes down to the ground to evaluate where you will step.  You tense up the trunk of your body for stability.  All of these actions are your adaptations to that environment.  Your fingertips are gathering information about your position and balance.  Your eyes relay info to your brain about where it is safe to step and your core is in guard to stabilize your body.  These are all visuo-spatial skills. 

People constantly interpret a large amount of sensory information about their environment.  You use peripheral vision, cues from receptors in your muscles about your physical orientation (proprioreceptors), balance information from the inner ear (the vestibular apparatus) and visual cues about what is around you in space.  Those with WS seem to have difficulty coordinating this information.  They struggle when presented with situations where they need to make shifts in their space, such as changing their posture on a crowded bus to let someone walk by.  This body awareness issue along with their difficulties in motor planning, spatial cues and directional cues make it hard for them to do planning activities such as when it is appropriate to cross a busy street or the ability to judge the speed of oncoming traffic.  This is one reason many of them do not drive as an adult (along with anxiety issues- see a future blog post on this topic) 

The directional disability also contributes to reasons why many of the individuals have difficulty understanding left from right, even as an adult and they have some difficulties understanding mirror images.  This directional disability also contributes to handedness.  Most children establish whether they are right handed or left handed by the age of 4-6.  Individuals with WS often don't achieve this until the age range of 5-8.  Many studies suggest this is due to the brain disorganization.  Most with WS will alternate between a preferred hand, use one hand for household tasks, such as eating, and another for writing.  They may alternate the use of their hand when activities require them to cross over the body to complete a task, such as building a large block tower.  Most with WS become left handed. 

There are several theories on why those with WS have this visuo-spatial disability:

• deletion of the LIM-kinase I gene.  There is research out there, although in its infancy, that the deletion of this gene is correlated with the visuo-spatial disability.  However, there are case studies of children missing this gene who do not display spatial delays, so evidence is inconclusive.
• A disconnect in the dorsal stream nervous pathway
• An atypical pattern of brain activity

It all has to do with the cellular pathways in the brain

Many of the researchers in brain studies are psychologists who study the brain function of children and adults with WS.  Their goal is to attempt to identify the areas of the brain that are medically classified as "dysfunctional" or have slower motor pathways.  Before getting into the brain studies, lets take a look at some basic brain anatomy that will help you picture why this "dysfunctional" classification is assigned.

Background on Neural pathways

The human brain is made up of many neurons, or nerve cells.  These cells have cell bodies that are unique in shape and extending from the main portion of the cell are processes or "arms", so to speak.  There are processes, called dendrites, that receive messages.  Sensory neurons sit outside the central nervous system and collect information from the environment using their dendrites.  These sensory neurons have endings called receptors that monitor the environment.  This message containing information about the environment is sent down a long process (or arm) called the axon to a second neuron in the central nervous system.  Neurons in the central nervous system, called association neurons, are located in the brain and spinal cord.  They function to process this sensory information- by interpreting what is happening around you and how the body should react to it.  Then, the association neuron will communicate a new message, send it down its axon to a motor neuron.  The axon releases a chemical (called a neurotransmitter) which travels across a gap and talks to the motor neuron.  This motor neuron then takes that message and tells the muscles how to move.

Inside the brain there are many of these "thinking" neurons.  Depending on where they are in the brain, they have different jobs.  Some areas of the brain receive visual information whereas a separate part receives auditory info, for example.  There are also areas that are for figuring out the sensory info and then a separate area for linking that info to a memory so you can label it or attach it to an emotion.  All of this takes quite a bit of coordination within the brain in order to take in information from multiple senses and combine it to create a scene of what is happening in your environment.

Neurons have jobs

There are special nerve tracts within the center portion of the brain that connect the all the sensory pathways so the brain can share the info.  These pathways are called white matter.  White matter is buried deep inside the brain and is the color white because of tiny cells that wrap themselves around the neurons, called myelin.  The myelin is a fatty layer that allows the message to move quickly down the axon.  It makes for very fast messages and is essentially a "highway" system of neurons that move info from one side of the brain to another. 

  

The outer surface of the brain, which sits around the outside of the white matter is called grey matter.  The grey matter creates what we called the "cerebral cortex".  This is where the "magic" happens.  The cortex is made up of unmyelinated neurons, or neurons that are "naked" without that fatty layer.  The messages are sent more slowly here.  In these regions, your brain decides what to do, problem solves and determines how you will behave.  It is well known that the higher IQ or the better "thinker" you are, the thicker this portion of the brain is.  The grey matter builds up in folds called gyri.  These ridges of the brain are the same on everyone, but they are thicker/thinner based on your genetics and how much you challenge yourself as a learner.  In between the gyri are shallow grooves called sulci. 

In the speech section of this blog, I mentioned that in brain studies, researchers have found that individuals with WS tend to have very thick gyri in areas that are strengths for them- particularly in the auditory region and language centers of the temporal lobe.  There are regions of the brain that have much thinner gyri.  These thinner areas of the occipital (visual) and parietal (sensory) lobes result in a visuo-spatial disability in those with WS.

Figure shows comparisons of gyri in controls (samples from the general public) versus gyri of individuals with WS.  Red areas indicate increases in gyri thickness and blue indicates smaller gyri.  Green shows areas that are comparable between the two groups. 


Streams- flow of information within the highway of the brain

The flow of sensory information that moves through the white matter in the brain can take a variety of different routes.  Two of the more important visual routes are the dorsal stream and the ventral stream. 

There is a section of grey matter in the back of the brain that makes up one gyrus in the parietal lobe.  This gyrus is smaller in the brain of someone with WS than in a typical person.  This section of the brain is involved in the dorsal visual stream.  In the dorsal visual stream, the brain uses visual information to interpret its surroundings, such as an obstacle, and determines how you will move around it.  This stream of information is very slow in an individual with WS due to the small amount of grey matter, making it more difficult for them to navigate.  Research has also shown that in individuals with WS, the brain often doesn't even use this stream when you'd expect it should.  In MRI's this area of the brain shows low activity during movement tasks.

The highlighted area on this picture shows the gyri that is abnormal in WS.  This disrupts the dorsal stream of visual information that is used to produce motor activities.

The ventral stream, in contrast is a strength for those with WS.  It involves information moving from the parietal lobe to the temporal lobe where the gyri are much thicker.  This stream of neural activity is used to recognize people using visual information and labeling.  In case studies, these streams can be tested fairly easily.  If you ask someone with WS to identify the a pathway through an obstacle course they could look at it and tell you where the midpoint of the path is (using the ventral stream) but if you ask them to walk it (which uses their dorsal stream) they would move very slowly and clumsily through the pathway.

Particular motor difficulties that are directly related to deficits in the dorsal stream and are seen in the majority (97%) of individuals with WS include:

• poor dexterity
• slow speed in movements with the arms and legs
• inability to move in response to visual information
• difficulty manipulating an object in the proper orientation to place it in a slot that is shape specific (such as a card in a slot or a block in a shape sorter) 

Problems with nervous pathways are a increasing area of study in WS research.  The nerve interactions between the frontal lobe and parietal lobe point toward behavioral difficulties that are very common in individuals with WS- including high distractability, inability to maintain prolonged attention to a task,  acting impulsively and having difficulty understanding global concepts (topics that are not concrete in thinking).  (Look for a future blog post on ADHD and behavioral profiles of individuals with WS.)


Making plans...

  

Another skill that is inhibited by dorsal stream dysfunction has to do with motor planning.  Motor planning means that the child would see what is in their environment (such as a ball flying at them through the air) have to think of how they want to respond (such as catch it), plan on what muscles need to be used to do so and where that ball will land in space and then relay the message to those muscles to complete the task.  Typically developing children will accomplish this task but many of those with WS often watch the ball as it hits them.  This disability in motor planning- often called apraxia, seems to be a difficulty in about 92% of individuals with WS.  This skill is even more difficult in certain situations such as bouncing the ball because they have to predict what direction it will land.  These tasks that require a person to use a familiar task and modify them to match the spatial information is very difficult for them.

The motor planning dysfunction will often delay their ability to throw and catch a ball.  Although most kids with WS will throw and catch a ball by the age of 6.5, they will likely have a lifelong inability to throw (51%) and catch (67%) in a coordinated fashion.  When throwing a ball, one must rotate their body, move their arm and often step forward with their leg.  Those with WS display an inability to do this at all ages.  They often will throw their arm but lack the body positioning and rotation in the upper body to make a decent throw.  The catching action is mainly due to the visuo-spatial tracking and motor planning required to predict where the ball will land and those skills needed to right the body and extend the arms quickly enough to catch the ball in time.  They simply process this information too slowly and inaccurately in order to accomplish the task.

Studies have shown that although visuo-spatial difficulties are an issue for nearly everyone with WS, there are tools that children can learn to help minimize this disability.  Case studies frequently note that those individuals who learned or utilized verbal cues were better able to navigate obstacle courses.  For example, if the person who is walking through the course studies it first and vocalizes a plan, then as they walk they talk about how to move their body, they move less awkwardly and accomplish the task with better timing.   It is also important to note that individuals that participated in these studies had varying degrees of difficulty.  Some were only slightly impaired in the task and others had higher difficulties with most having a moderate level of challenge.  Therefore, while spatial navigation is a disability for all individuals with WS, the magnitude of that disability lies on a spectrum and can be different for each individual.

Walk this way

Poor motor abilities in an individual with WS extend to many other issues that are rooted in the nervous system.  Individuals with WS, especially in the early years, have a very distinguishable gait, or walk, that is described as clumsy and uncoordinated.  There are a variety of reasons for this.

First, young children who are new to walking have ingrained protective reflexes that they use to maintain balance.  If they find themselves fighting gravity or on an uneven surface, they will right their head over their body, tighten their core and throw their arms outwards to steady their bodies and protect them from a fall.  Kids with WS seem to lack this reflex (I can personally attest that my daughter has fallen many times without ever extending her arms out to catch herself, leading to minor head injuries). 

The majority (between 60-80%) of children with WS have gross motor delays or unorganized motor skills and delays associated with climbing stairs, walking down stairs, running, jumping (especially off an elevated surface), transitioning from one variegated surface to another, walking on uneven terrain (such as grass or mulch/sand), skipping and running.  These delays or motor planning deficiencies are associated with balance issues.  Balance is related to the processing of sensory information by the nervous system.  Approximately 60% of those with WS have balance processing disorders and another 80% have trouble interpreting gravitational signals.


Those with WS have trouble navigating quickly through obstacles that require them to take longer than average strides.  They improve this skill when sensory cues are present such as lights to step in to determine stride length.  But even with sensory cues their walk is much slower than typical.  This indicates there may be some dysfunction within the cerebellum, which is the part of the brain that controls balance and coordination.  Other cerebellar studies have found that in WS, the neocerebellar lobules are enlarged.

  These are regions on the sides of the cerebellum that have major nervous pathways that communicate with the thalamus and the cerebral cortex.  The thalamus is the main area in the center of the brain that associates sensory information with memory.  Major nerve tracts link problem solving to memory to the cerebellum through this nerve tract. 

Scientists have linked this stream directly to motor coordination when learning a new motor skill.  It's used for following a series of steps used to follow a motor procedure, such as riding a bike.  It coordinates limb movements in order to achieve the desired action.  This area of the cerebellum is also heavily linked to an area of the brainstem called the superior colliculi.  This is a visual reflex area that helps coordinate the motor movements in the eyes.  Dysfunction in this can lead to poor muscle control in the eyes and can be another cause of strabismus (see the eyes section of this blog).  The neocerebellar area also helps to coordinate motor movements used to coordinate speech.

Besides brian studies, there are other reasons individuals with WS may have a harder time with motor activities. 

• Tone- The ability for the nervous system to control muscle contractions in appropriate times; previously discussed in this blog (See the muscles section).
• Sleep- sleep is a well known difficulty for up to 97% of individuals with WS which can further affect cognitive development and motor planning.
• Vision- Although vision is not an issue for all children with WS, if a child has strabismis or crossing of the eyes sends conflicting information to the brain about the person's surroundings.  This can lead to increased delay in motor skills- particularly spatial understanding.  This is even more evident if the individual has lost vision in the weaker eye.  This causes the body to lose their depth perception.  Everything will appear flat and in 2 dimensions.  This will cause additional issues with motor development. (see the eye section of this blog)

 

Fine motor delays due to visuo-spatial disabilities

Spatial difficulties offer up difficulties in a variety of motor tasks.  Early in a child's life occupational skills will seem less serious than gross motor skills but as the child ages, their abilities will change and fine motor skills will become increasingly important as they gain independent living skills. 

Self help
Most children (80%) have delays in fine motor skills required for self help.  These can be related to directional disability (used to set a table, for example) but most are due to the visuo-spatial disability.  Through therapy, most of these skills can be mastered, but approximately 30% of adults still find difficulty in some skills such as tying shoes, buttoning clothing, etc. For example, many will have high difficulty using knife skills, such as those used to make a peanut butter sandwich.  They may have trouble grasping the knife, creating the motion to spread the butter, applying the proper amount of force and stabilizing the bread.  This takes motor planning and the ability to judge the environment of the bread and make small motor adjustments to have the proper movement.  Other self help skills such as writing, cooking, buttoning clothing, using a zipper and tying shoes are difficult for a person with WS due to the need to plan motor movements during these activities and have spatial awareness. One study found that, on average there is a 2 year delay in children with WS, aged 4-12, in both fine motor skills and gross motor skills that require visuo-spatial ability.

One major fine motor activity a child with WS will find difficulty in is the ability to manipulate objects in space, such as placing mail into a narrow slot.  This skill is processed by the dorsal stream in the parietal lobe of the cerebrum.  Other examples of difficult motor task include movement planning time.  In one case study, researchers had adults draw a line between two circles using a stylus.  When the shapes changed sizes, those with WS had significantly slower times completing the task.  This study linked difficulties with this task to the inability for those with WS to anticipate the movement of an object and plan their motor response to it.

Drawing

Most typical children will draw recognizable pictures of objects by the age of 5 or 6 whereas those with WS draw them closer to the age of 9 or 10.  This is due to the visuo-spatial delay.  They draw comparably, though, to peers with mental disabilities.  IQ and drawing ability do not match in WS indicating it is an area of disability.  It is also notable to say that they do eventually achieve the ability to do this task by adulthood.

This photo is from the study completed by Dr. Mervis et al. and it shows a drawing of a bicycle, completed by a 12 year old with WS.  All the components of the bike are present, but those with WS have a difficult time picturing how they are connected- a spatial skill.
Therapists have identified a strategy that help individuals with WS improve their ability to draw.  This should be used in OT sessions.  The increase in gains when using the face as a drawing tool stems to brain studies that show individuals with WS use their brain differently to interpret faces.  Typical adults will process facial recognition with the right side of their temporal lobe.  Those with WS use a much larger area of the brain and primarily use the left side of the brain to do this.  The study also had interesting evidence that those with WS use the same amount of processing to interpret the face of a picture of a person that is upright versus on that is flipped up side down.  In typical adults, there is a delay in processing the flipped images as the brain has to try and associate the image with what they'd look like right side up.  Those with WS use more brain activity looking at a face in any position than a typical person would and they use the same brain activity despite the picture orientation.


Ways to help improve their drawing skill is to allow them to draw motivating pictures- focus on drawing people, facial expressions, etc rather than shapes.  Kids showed greater gains when they had developmental interpretation therapy session to help them process how the picture should fit together.  They also improved with frequent practice.  Case studies show that in children, ages 4-6, who participate in the developmental interpretation sessions and practiced drawing people and houses showed significant gains in elaboration of the picture, increases in inclusion of objects, improved their ability to draw an object in its proper context (like a person in a house) and increased in the ability to combine features (all the parts of the picture connected in the proper ways such as heads were on necks and legs attached to bodies).  Improvement has also been shown to have the subject verbally express what they are drawing and how it should connect the lines.  When they talk through the process, the picture ends up more organized.

In the same study the kids were assessed again between the ages of 12-15.  After 6 years of growth, the ability to draw more organized pictures improved in all subjects of the study.  So, although the skill is delayed, it does improve with time.  In all age groups, the subjects were able to draw more organized pictures of people and flowers versus objects such as houses, bikes and animals. 

In conclusion

Visuo-spatial difficulties are an issue for all individuals with WS but with purposeful and educated therapists, there are skills and techniques that they can learn to help them overcome this obstacle and improve their self help and motor skills as they age.

Sources:

• http://www.nature.com/nrn/journal/v7/n5/full/nrn1906.html Primary source on brain studies linked to WS
• http://www.psych-it.com.au/Psychlopedia/article.asp?id=412 A summary of psychatric studies related to brain and behaviors in WS.
• http://www.dartmouth.edu/~rswenson/NeuroSci/chapter_8B.html Information on cerebellum function
• http://www.n-acetylaspartate.com/ Information on  the neurotransmitter, N-acetylaspartate
• Neurobiological models of visiospatial cognition in children with williams syndrome
• http://www.springerlink.com/content/p57121g83734300g/
• http://www.physio-pedia.com/index.php/William's_Syndrome#cite_note-Seventeen-16 An overview of Williams syndrome manifestations related to physio-motor intervention
• http://books.google.com/books?id=9E9q5112WBgC&pg=PA136&lpg=PA136&dq=motor+delay+williams+syndrome&source=bl&ots=LdcBfjN6p1&sig=4uSFQrsE1J7LibATNjKYZnFb6I8&hl=en&sa=X&ei=QVtIT62ACJD_sQLj_anNCg&ved=0CCkQ6AEwATgK#v=onepage&q=motor%20delay%20williams%20syndrome&f=false A google sampling from the book "Understanding Williams Syndrome"- used the sections of motor delay

  

Chiari Malformation

Chiari malformation (spoken as kee-AHR-ee) is a disorder of the skull where the cranium that holds the brain is small at its base.  The brain is cradled and protected in a casing of bone called the cranium.  The cranium is made up of 6 fused bones- the frontal bone, sphenoid bone, ethmoid bone, parietal bone, temporal bone and occipital bone.   The occipital bone is the most inferior or lowest bone in the cranium and it protects the back of the brain.

The occipital bone in humans is curved at the base which allows it to cradle the round brain tissue inside.  This curved portion of the occipital bone is called the posterior fossa and it sits just under the ridge in the back of the head that you can feel (called the occipital protrubance). 

The posterior fossa cradles the most posterior (back) and inferior (lowest) portion of the brain called the cerebellum.  The cerebellum is a smaller domain of the brain that coordinates motor function- such as balance and coordination.  It has many nerve tracts that communicate with the cerebrum where your brain "decides" on how to move and react to its environment.  Also in the cerebellum are tiny channels and chambers that act as canals to move nutrient-rich fluid (called cerebral spinal fluid or CSF) around the brain feeding it and cleansing it of waste.   CSF acts much like the blood supply but unlike blood, it does not carry cells other than those of your immune system; essentially protecting it from viral and bacterial infection.  The CSF travels through the cerebellum in a canal, called the cerebral aquaduct, that moves from the cerebral area down into the brainstem.  The CSF accumulates in a chamber that sits just under the cerebellum, called the 4th ventricle.  From here it drains down another canal into the spinal cord through the central canal.  At the base of the occipital bone is a large opening called the foramen magnum where the brain stem exits the cranium and leads to the spinal cord. 

In WS, mis-shapen cranial bones are prevalent making Chiari an unfortunate complication of the disorder for some.  When the cranium is formed during fetal development, some people's posterior fossa is mis-shapen.  This can happen in two ways.  First the base of the skull that fuses with the facial bones, called the clivus, can be shorter than normal consequently crowding the cerebellum.  The second malformation that can occur is in the tentorium cerebelli.  This is a fiberous covering that separates the cerebrum from the cerebellum.  This membrane when situated in a steep fashion pushes down on the cerebellum and crowds the space.

Due to the crowding, a portion of the cerebellum called the cerebellar tonsils can be compressed into the base of the skull and/or extend down into the foramen magnum (the hole where the brainstem exits the skull and becomes the spinal cord).  If the cerebellum is crowded in this space, the tonsils extend down into the hole and essentially block the passage way of the CSF flowing out of the 4th ventricle into the central canal of the spinal cord. 

The arrows in the picture on the left show the normal flow of CSF through the brain.  The picture on the right shows that when the cerebellum sits too low in the posterior fossa it cuts off the flow of the CSF around the cerebellum.

The severity of crowding can cause pressure to be exerted on the cerebellum creating neurological or motor issues.  It can also close off the channels where CSF moves causing it to build up pressure and stop its flow which essentially will cut of supply of CSF to parts of the brain stem and spinal cord. 

picture from www.chiariinstitute.com

Types of Chiari
Chiari Malformation can occur in various degrees of severity.  It is considered a congenital disorder (where it is formed at birth) but symptoms are often not witnessed until adolescence or early adulthood because the pressure can cause neurological damage over time.  In Williams Syndrome (WS), type 1 Chiari Malformation occurs in 10% of cases.  Type 1 is less severe and often is not accompanied by any symptoms.  It's found more commonly than the other types and is often diagnosed in conjunction with other neurological disorders rather than on its own.  Type I is often considered an adult form because it is often not usually discovered until later in life. 

A brain scan showing Chiari type 1.

There are also two other types of Chiari Malformation.  Type II, also called Arnold-Chiari Malformation is typically found in conjunction with a disorder of the spinal cord called spina bifida where the spine doesn't close properly during growth in-utero and the spinal cord protrudes from the back.  This type is usually discovered during pregnancy in an ultrasound because it is accompanied with other spinal abnormalities that are more obvious.  The third type, which is rare and most severe is Type III which leads to long term debilitating neurological issues and requires surgery and long term treatment. 

There is not much known if Chiari is a hereditary disorder.  There are a few documented instances where it seems to run in a few families but not much is known about genetic links to this disorder.

Symptoms

Most people with Chiari will experience headaches typically at the base of the head or neck and are often treated for pain.  Many end up with severe headaches after coughing and sneezing.   Other symptoms include changes in the voice and difficulty swallowing often with gagging or choking.  Because the cerebellum controls coordination, body movements can become difficult.  This can include spatial difficulties, dizziness, blurred vision, poor fine motor control (such as holding a pencil and writing), numbness and tingling in the hands and slurred speech.  Other symptoms that are considered more rare are sleep apnea, ringing in the ears, poor bladder control, scoliosis and chest pain.

Unfortunately for those with WS, the symptoms of Chiari malformation are common issues in WS such as coordination issues, gagging and swallowing issues and fine motor delays so it may be difficult to spot them if your child cannot communicate that they have a headache.

If Chari malformation is suspected a neurologist will often complete an MRI to assess the bone formation.  They will conduct a special test called a cine-MRI which tests the flow of the CSF through the brain to see if there is blockage. 

In some people with Chiari, syringomyelia may develop due to nerve tract damage.  In this complication, a canal or cyst will develop in the spinal cord and fills with fluid.  This can cause additional pressure in the canals that carry CSF and can cause further nerve damage.

Arrows indicate regions of syringomyelia

Treatment
Surgery is the only treatment that can stop neurological damage to the central nervous system and depending on the severity several surgeries may be needed to effectively repair the cranial crowding.  If there is any doubt about need for surgery it will usually be delayed.  There are three reasons a neurologist would suggest surgery for this disorder: 1. There is obvious neurological damage especially if it worsens over time; 2. If other spinal cord issues are present as well (such as tethered cord, scoliosis, spina bifida, etc); and 3. If the symptoms of Chiari greatly affect the person's ability to cope day to day (such as if the headaches are too great to manage). 

The surgery itself is called decompression surgery.  The goal of the surgery is to relieve pressure exerted on the channels that carry CSF so that proper flow is restored and to relieve any pressure exerted on the cerebellum by the skull.  This is accomplished by performing an occipital craniectomy which means they remove some of the skull bone at the base of the skull to increase the space in the occipital posterior fossa.  This may  not require going into the brain itself; it focuses on changing the shape of the bone.  The surgery can also include a C1 laminectomy which is surgical change to the first bone in the vertebrae (cervical vertebrae #1).  In this procedure, they remove an archway that surrounds the spinal cord and possibly the ridge that forms the portion of the spine that you feel when you touch the back.  The goal of this is to relieve pressure where the cranium and vertebrae meet (where the headaches often exist).  In these sections where the bone is removed, the tough brain coverings that sit underneath the bone remain intact. 

At this point of the surgery some surgeons (5-10%) stop; about 45% also remove dura mater (called a duraplasty) which is the most common type of surgery for this disorder.  Dura mater (meaning "tough mother") is the very tough covering that surrounds the brain and spinal cord.  It has the consistency of thin plastic, like that of a water bottle.

 The dura mater would be cut and then a synthetic patch of it would be sewn in to increase the area and free up more space.  This procedure, called a graft, can use tissue from the patient itself, bovine pericardium (a sack lining that surrounds the heart of the cow) or synthetic material.  The material used is really the preference of the surgeon.  There is no research that shows one is better than another. 

From here another 45% of doctors will also remove the second layer surrounding the brain called the arachnoid space.  This layer is part of the channel system that skirts CSF around the brain and it often has lesions in it that when broken, can free up room for the cerebellum.  In some cases, the surgeon may also shrink the cerebellar tonsils themselves by either cauderizing them (which makes them shrink) or resecting them (cutting a portion out) to relieve the crowding and open up the channels for CSF flow.  This manipulation of the cerebellum itself is more risky because by interrupting the arachnoid layer, the patient can be exposed to risks of bacterial or viral infections in the brain such as meningitis. 

During surgery, ultrasounds are often use to constantly assess the flow of the CSF and the position of the cerebellar tonsils as room is freed up.  The success of the surgery really depends on the patient's severity and how the brain is compressed.  Some patients only need one surgery but approximately 30%, typically those with spinal or cranial deformities and other spinal complications, will need follow-up surgeries because the condition will relapse later in life.

What to do if you suspect Chiari
If you suspect Chiari malformation in your child with WS, it is important to see a neurologist.  The Mayo Clinic has a great web page with information you should bring to your first meeting and a list of questions to ask so you are well informed about the condition.



Sources used in this blog post:
National Institute of Neurological Disorders and Stroke
Chari and Syringomyelia Foundation
The Mayo Clinic

Upright Health: Posterior fossa and Chiari Malformation

Curved fingers and toes- Clinodactyly

Although it is a harmless condition and usually requires no treatment or even sought after advice from a specialist, many parents with children who have Williams syndrome remark about their curly fingers and toes.  Most often present in the 5^th finger (pinkie) or the 3, 4^th or 5^th toes, the digit is often seen curving inwards or overlapping with a neighboring finger or toe and the finger itself may look “stubby” or have a triangular or trapezoidal shape to its tip. 

Curly Toes (see a great picture of curly toes here )

Curly and overlapping toes are considered highly common in general population and don’t suggest any DNA issues.  They are usually found passed down through family lines.  The most common place to have a curly toe is when the 4^th and 5^th toes overlap.  Although there hasn’t been a great deal of research as to why this happens, there are some accepted theories as to why this occurs.  Many believe it is either due to the baby’s position in the womb or there is a slight deformity in the joint of the toe.   When the misaligned joint is coupled with either hypotonic or hypertonic muscles of the foot (see the muscles section of this blog), tension is placed on the tendon of the small toes pulling them out of alignment. 

A tendon is a strong cord of connective tissue that attaches muscles to bone.  Tendons often act like an ace bandage, creating tension around a joint to stabilize it and allow the muscle to move the bone to create motion in the body.  If the muscle is too weak or too tight it can cause the tension of the tendon to either be too low or too high.  This unbalanced tension then will cause the bone to become misaligned.   This can cause a more extreme overlapping of the toe than what you’d see in your family members. 

Usually clinodactyly doesn’t require any medical attention unless it progressively becomes worse turning into a joint contracture or if it interferes with walking.

A hooked finger

While curly toes are not used as a clinical diagnosis of any genetic anomalies, hooked fingers are.  A curved finger is considered typical in 10% of the general population but more likely than not, it indicates a DNA anomaly.  Found most common in individuals with Down Syndrome, a hooked pinkie is a structural abnormality that is present in approximately 60 different syndromes.   A hooked or curled pinkie finger indicates some sort of bone deformity usually attributed to delayed in utero growth (growth in the womb).  It often shows up on ultrasound and can be used to suggest further prenatal testing or guidance of a perinatalist although it is rarely a means of diagnosing any syndrome since it is so common in many genetic issues.  Basically, it can be used as a red flag.

The cause of clinodactyly in the pinky finger is due to a structural issue in the growth plate on the bone, called the epiphyseal plate.  The growth plate is a layer of cartilage at the end of a long bone (like those in the fingers and limbs).  As the child’s body grows, the cartilage is continually replaced with a bone matrix causing the bone to grow in length.  In clinodactyly, the bone’s growth plate is misaligned.  This causes the toe to grow in a curved fashion rather than straight.  In addition to growth in an abnormal direction, the tip of the finger will often end up looking triangular or trapezoid in shape. 

Again, unless there is extreme overlap on the finger to the point that it inhibits the child from gripping properly or having proper hand function, no treatment or worry is warranted.

Sources:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1255945/

http://www.podiatrynetwork.com/document_disorders.cfm?id=194

http://childrenshospital.org/az/Site1160/mainpageS1160P0.html

Updated muscles section

Greetings followers!  I have added more to the muscle page.  If you scroll past part 1 I've added a section on high tone in the muscles and joint contractures.  I spent most of the time talking about toe walking, which is the most common type.  I hope you find it useful!

If you have any topics that you'd like to learn more about, leave a comment.  I'd be happy to make a post for you.

Take care and happy fall!
Sarah

Absorbing calcium

Although the cause of hypercalcemia is a mystery 1in Williams syndrome, we do know a little about how the calcium is absorbed in the gut. Many people think that the stomach is the main area of digestion in your body. Although it does digest proteins, the majority of the food is broken down and absorbed by the small intestine. The lining inside of your small intestine is a network of finger-like bumps that are filled with blood vessels and covered by a very thin layer of skin that sits between the vessels and the food/enzyme mixture in your gut.




Most calcium in your small intestine is absorbed in the lower regions called the ileum and jejunum. These are the main portions of your intestine that absorb nutrients and minerals. Calcium here will move passively into the blood stream. This means that it can easily slip through little spaces in the skin layer (called the epithelium) and into the blood. If your diet provides your body with enough calcium, this is the main type of transport you'll use.




If calcium levels are low, your body has to work a little harder to get the amount it needs. This is where vitamin D comes in. Vitamin D operates channels that collect calcium in the upper third of the small intestine, called the duodenum. These channels are activated when vitamin D binds to proteins in the epithelium (skin) layer. These proteins work with active transport, where the body uses energy to pump the calcium into the blood stream, increasing its levels in the blood. This is why, if you increase the vitamin D in your diet, you end up increasing the calcium in your blood stream.




This vitamin D metabolism is one of three theories I could find that try to explain infantile hypercalcemia in WS. Researchers have found that when children with hypercalcemia are managing their calcium levels and only slightly rise the vitamin D in their diet, their calcium levels increase dramatically. They found that by only making small increases in vitamin D, children with WS absorb 2-3 times more calcium than what would be expected in a typical child.




Another factor that influences calcium absorption is the type of food you eat. If you are a milk drinker, you're going to have more passive calcium absorption- the easy kind in the lower intestine. Milk contains sugars called lactose and an enzyme called lactase both of which help the body collect the calcium and absorb it into the blood stream. Other foods also contain calcium, such as spinach. Foods that are high in fiber and contain calcium tend to be harder for your body to digest. The fiber, called oxalate, binds to the calcium and holds on to it as it passes through the gut. Therefore, if your primary calcium sources are in high fiber foods, you will essentially absorb less of them and excrete more due to the food's chemical nature.







Oxalate has other affects on your body, too. If the level of calcium is low, your body will start to absorb more oxalate instead of excreting it. Essentially, if you are in a pinch for calcium, you'll take what you can get even if it's in a form that you don't really prefer. The increase in oxalate signals the kidneys to work harder to get rid of it. Calcium oxalate then builds up in the kidneys and can cause stones, or nephrocalcinosis (see the growth and diet page on this blog). This is why some doctors will place a child with hypercalcemia on a low oxalate diet- to prevent the uptake of calcium and reduce dangers of developing kidney stones.



It's important to note that although many WS infants with hypercalcemia have higher than normal levels of vitamin D, there are exceptions to the rule. There is a significant population of individuals who have high levels of calcium and LOW levels of vitamin D. Since most foods contain both, this can create quite the dilemma to try and maintain proper levels of each. Stay tuned for future blog posts discussing this topic and other theories of why our little ones have hypercalcemia!

WS- a major player in what we "know" about vitamin D

Over the past couple of days I've had a couple of parents send me questions about calcium and vitamin D and how they affect WS. Those questions will be answered in future blog posts but until then, I found some interesting information about how WS has changed the way many researchers have viewed vitamin D. I've enjoyed getting questions from other parents because I've learned so much in the quest to answer them! Keep them coming :)



Although this is a science-based blog, here is your history lesson for the day:

• 
  
  

  In the 1960's it was thought that supravalvular aortic stenosis (the characteristic heart defect of WS) was caused by the mother ingesting too much vitamin D during pregnancy. At the time, researchers didn't know about Williams syndrome and its genetic component. A study performed in the late 1950's drew a connection between SVAS and hypercalcemia (or high calcium in the blood). WS is the only identified disorder that has unexplained hypercalcemia before the age of 1. So, the researchers put two and two together and concluded that high levels of vitamin D lead to heart defects and all the symptoms of what we today know as Williams syndrome- SVAS, low IQ, and hypercalcemia. The study started a Vitamin D scare that changed the Food and Nutrition Board recommended values for Vitamin D to lower levels in Britain and the US. Until the 1980's when genetics identified that SVAS is due to a genetic defect did the vitamin D theory change.

Recently, a new vitamin D theory has surfaced and again, it's basic idea is based on what else, Williams syndrome:

• A group of researchers began in 2007, studying a link between vitamin D deficiencies with the increase of autistic children. The researchers studying this connection are using Williams syndrome as the basis of their hypothesis. Their reasoning is that the highly sociable personalities of WS are opposite those of autistic children. They think that social behavior is directly related to vitamin D levels- WS, having high levels of calcium and vitamin D in the first year of life leads to high social nature versus autism that could potentially have low levels of vitamin D and exhibiting anti-social behaviors. Their hypothesis is that vitamin D levels in the body determine the social nature of each disorder.

They don't comment on the fact that some kids with WS are also autistic, making me skeptical, but still an interesting study! It just goes to show you, what you "know" today may not be considered right in the future. And that my friends, is what makes science so interesting to me. There is always more to learn.