Chronic Traumatic Encephalopathy

Introduction
Chronic Traumatic Encephalopathy also known as CTE has been a very widely used term in today’s society. Most importantly surrounding high impact sports and military. In 1973 research was conducted by Corsellis surrounding boxing and repeated head injuries. He called it dementia pugilistica or ‘punch-drunk syndrome”. Boxers often times exhibited cognitive, behavioral, or motor abnormalities and were well known by sportswriters, and others within the boxing community and were referred to by a variety of terms, such as “punch drunk,” “goofy,” and “slug-nutty” which is where Corsellis got the term for what we now call CTE.  It wasn’t until Dr. Omula explored the brain of retired Pittsburgh Steeler; Mike Webster, when the emphasis on what they called dementia pugilistica jumped to action. It was at this moment Dr. Omalu knew what he found was special and would change the lives of many athletes. His research was able to highlight the fact that not only boxers are affected by this disease.

Dr. Omula’s findings showed that CTE has been found in individuals who have experienced head injuries from a number of activities. This includes over 200 cases from football, over 25 cases in the military, over 20 cases in hockey, over 15 cases in boxing, and over 5 cases in rugby, soccer and pro-wrestling. Cases were also found in less impact sports but much less than the other sports. Many of these cases were highlighted in sports with a high chance to have head trauma. Most people diagnosed with CTE suffered hundreds or thousands of head impacts over the course of many years playing contact sports or serving in the military. A concussion is a mild traumatic brain injury that can be caused by a hard hit to the head. A concussion can knock someone out for 30 minutes or less; some short-term symptoms often appear at the time of the injury, but can develop days or weeks later. However, just one concussion will not put one at risk of CTE, multiple head traumas must occur to be put at risk. There are approximately 1.6 to 3.8 million sports-related concussions that occur annually in the United States. Not everyone that has been concussed is going to get CTE; as the numbers show there are way more concussions than there are CTE cases. Since CTE is linked to repeated head trauma, that means the cells in the brain are under attack every time a hit to the head occurs. Therefore, CTE is a form of a neurodegenerative disease. A neurodegenerative disease is classified by the death or degeneration of the nerves in the brain.

Since CTE effects the brains nerves it is not curable due to the slow regeneration rate of the nervous system. CTE is a neurodegenerative disease marked by the widespread accumulation of the tau protein. The action of these proteins is what separates it from the other neurodegenerative diseases. However, many neurodegenerative diseases share the same symptoms and pathology and make it hard to diagnose. CTE shares many features with Alzheimer’s disease , progressive supranuclear palsy, post-encephalitic Parkinsonism, and the amyotrophic lateral sclerosis/Parkinson’s-dementia complex of Guam. The main comparison is Alzheimer’s, in fact Dr. Omula expected Webster’s brain to look like one of an Alzheimer patient because the symptoms were so similar. These symptoms include memory loss, irritability, outbursts of aggressive or violent behavior, confusion, speech abnormalities, cognitive decline, gait abnormalities, unsteadiness, headaches, slurred speech and Parkinsonism. The intensity of these symptoms can depend on when the athletes begin the high impact sport and how long the career is. Those who start younger than 12 and have a longer career increase the risk of getting CTE.
Pathology
The basic anatomy of neurons consists of the cell body, the axon, and the dendrites. There are also microtubules that are scattered throughout the neuron, these help protect the neuron and keep the structure of the neuron. The axon is the weakest point of the neuron; this means when someone gets a concussion these axons tend to get damaged or break. However, microtubules are much smaller and weaker than the axons, and this means just a minor head injury can lead to these getting destroyed even though the axons may not be effected. A protein called tau is associated with these microtubules and helps keep them together by sticking to the outside. In a healthy brain that has not been damaged due to repetitive head trauma this protein supports the microtubules, and then the microtubules help the cells function, and then the brain functions normally. However, in a brain with CTE, this protein actually makes the brain less functional and slowly deteriorates it. Due to the repetitive head trauma tau protein changes there shape through phosphorylation and eventually clump together which makes brains with CTE to be unique to other normal or neurodegenerative brains. Brains that test positive for CTE have a unique pattern of tau that accumulates and clump together causing destruction of the cortex. These proteins scatter and clump at a slow rate which makes scientist to believe this is the reason for the late symptoms. It takes a long time for the slow moving clumps to infect enough brain tissue to change brain function.
Diagnosis
An exact diagnosis for CTE has not been found but there are many ways that scientists believe that CTE is different from other neurodegenerative diseases. A definitive diagnosis can only be made through an autopsy after death. Due to this CTE can only be partially diagnosed based on the symptoms they show. The symptoms of CTE are often shown around the age of 40. Due to CTE having a slow onset of symptoms it has been seen in people as young as 17 but since the symptoms do not occur until years after the repetitive head injuries it is impossible to tell a 17-year-old they have CTE. CTE is often associated with symptoms related to memory disturbances, behavioral and personality changes, Parkinsonism, and speech and gait abnormalities. To go further in depth Dr. Ann McKee sectioned the symptoms into three stages based on invasiveness. The first stage consists of affective disturbances and psychotic symptoms. The second stage is a little more specific and consists of memory loss, erratic behavior, and early Parkinson disease symptoms. The last stage being the most invasive consists of cognitive dysfunction that can lead to symptoms that correlate with dementia and Parkinson’s disease; speech abnormalities can also occur. These symptoms can be monitored but CTE can only be detected after death in an autopsy.

To perform a test for CTE doctors who specialize in brain diseases slice brain tissue and use special chemicals to make the tau clumps visible. Doctors have found many characteristics in the brains of CTE that isn’t just the clumping of the tau protein. These neuropathic findings, including a reduction in brain weight, enlargement of the lateral and third ventricles, thinning of the corpus callosum, caving of septum pellucidum, and scarring and neuronal loss of the cerebellar tonsils. In CTE the build of the tau protein often looks like a cluster of plaque that is spread throughout the cortex of the brain due to the build up neurons in the gray matter of the cortex. Just like any other disease CTE ranges from severity. Based on these findings in the autopsies performed Dr. Ann McKee was able to separate the progression of the disease into different stages, there are four different stages. The first stage being the one that hasn’t progressed very far is when a few clumps of tau proteins are found in the cortex of the brain.

The second stage involves more clumps present and not just in the cortex but in the cortical sulci. The clumps are starting to spread and migrate. The third stage Dr. McKee started to see the clumps blend into one large bundle and the hippocampus and amygdala were starting to get overcome by the protein. The hippocampus and the amygdala are associated with memory and emotions which is why many people with CTE show the symptoms of cognitive dysfunction. The final stage and the more invasive stage consists of dense protein bundles covering the whole cortex of the brain and even invading the spinal cord. This leads to the symptoms of Parkinson’s disease because they start to lose function of their bodies. Many of these stages involve the emotional and visceral area of the brain. This explains the symptoms that many people with CTE may have experienced like emotional liability and aggressive or violent outbursts. However, these outbursts are unexplainable when they happen due to the fact that CTE cannot be diagnosed in a living person.

Scientists are looking into research that will allow doctors to diagnose living people. There isn’t one definite test yet that will show a positive test for tau protein build up scientists are experimenting PET scans and fluid based bio markers. A PET scan involves the use of a low-level radioactive tracer that is injected in a vein. The scanner is able to trace the route of the tracer throughout the brain. Researchers are continuously working to develop PET markers to detect tau abnormalities associated with CTE that are the most cost-effective. There has been news about a tracer called FDDNP. This tracer is radioactive and has the ability to bind with the abnormal proteins in the brain and then appears in neural PET scans. However, there is no research showing that there has been a positive test in a living person after this finding. There is also research supporting the idea of fluid based biomarkers. This allows scientists to to detect proteins that are present in the blood at low levels.

The point of this test is to find the abnormal tau protein in the blood that would then lead to CTE. Usually these biomarkers can’t cross the blood brain barrier but due to the repetitive damage to the brain from repetitive trauma, the blood- brain barrier is weakened. Researchers also believe that there might be a genetic component to this disease. Since it is seen in research that not every person with repetitive head traumas or concussion produce CTE this means that there might be an underlying genetic issue. Dr. Ann McKee conducted ApoE genotyping which is a gene that has been found in many cases of CTE. Some cases carried just one allele and another was homozygous. She concluded that 15% of the population has this gene and may be more at risk fro CTE if multiple head traumas have occurred. There is no definite link to genetics and CTE quite yet but with further research the relationship can be discovered.
Treatment & Prevention
Just like many other neurodegenerative diseases CTE has no cure and is hard to treat the actual disease. The only treatment at this moment is trying to lessen the intensity of some of the symptoms. These symptoms include depression and anxiety which is easily diagnosed by a doctor and then given medication. Since CTE is closely related to Alzheimer’s disease people with the brain disease may benefit by using the same care provided to Alzheimer’s patients. Much of this care focuses on how these patients cope with their change in behavior and how to handle their anger. CTE can only be diagnosed after death therefore it is hard to treat something that little information is known about. A more effective way to try and rid this disease is to find better preventative plans.

Prevention is one of the first and most important step that need to be taken in order to control the amount of people dying from CTE. It is hard to avoid a concussion or a minor head trauma without completely eliminating the sport or cause of these traumas. There has been a number of rule changes due to the increased research on the negative impacts of repetitive head traumas. However, concussions will always be an ongoing injury that will have to be closely monitored. Therefore, the proper care and management of mild traumatic brain injury in general and particularly in sports will help reduce the number of CTE cases. Usually athletes are able to return to play within a week of the initial impact. However, studies show that for an athlete to be fully recovered from a concussion it may take at least 4 to 6 weeks. This helps prevent the chance of being reinjured because a second concussion within this time period occurs way more often because the brain is at a weak state. Also introducing kids to the high impact sports at an older age will also decrease brain damage. Usually kids below the age of 12 are more susceptible to concussions and since the brain is not fully developed it can cause more damage than that of an older kid.
Conclusion
In conclusion, only recently has CTE been the topic of discussion when talking about football and many other high impact sports. Dr. Omula was a key factor in changing the perspective on what used to be called dementia pugilistica. He knew what he found would change the way football is played and how just a simple concussion would be looked at as a more serious injury. Research has improved ever since Dr. Omula’s discovery in Mike Webster’s brain but it is hard to research and fund a disease that is not known until a post-mortem autopsy is performed. Since the discovery and further research of CTE many friends and family who have lost their loved ones due to this disease now have a few of their questions answered. Many people just thought these retired players were just depressed or had PTSD but with the research we have today this is not the case. These athletes were suffering way more but no one could see that. As research continues to increase, improvements around the world of head injures continues to increase and hopefully the amount of CTE cases decline. The worst part is the improvement will not be noticed for another decade due to the slow onset and that it can only be found after death.

References

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