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Epigenetics and TBI

As if there were not enough ground shaking discoveries to go around in the field of brain research, a huge paradigm shift is underway not only in brain research, but in all of biology. The breakthrough is called epigenetics. Basically, epigenetics turns our prior smug assurances about evolution and heritability upside down. We made fun of the Frenchman Lamarck for his notion of characteristics acquired during an animals lifetime being passed to its offspring. Epigenetics as a field has discovered that much of the formerly considered “Junk DNA” actually is responsible for genetic manipulation due to factors that we experience during our lifetimes.
The genetic structure of “DNA” as we know it does not change during this process. However, the “switches” that turn DNA on and off can be changed during a lifetime by certain events. There are over 2,000 proteins thus far that can be manipulated by the process known as acetylation. The modification of histones also comes into play. These changes are within our genetics and can be passed down to our descendants.

The field of epigenetics was relaunched in 1942 by Waddington, but it was not until a more recent study in Sweden that the full ramifications became evident. In a town known for its periodic starvation in the early twentieth century, researchers found that the stress of starvation generated heritable changes in the individual who had experienced starvation versus someone who had not. These changes in physiology such as body fat ratio, pre-disposition anxiety and depression were found to be directly related to the life experiences of the Swedes being studied. Many other examples have come forth over the past several years.
In terms of brain injury research, there are significant ramifications coming out of epigenetics. In a study entitled “Long-Term Epigenetic Modification After Mild Traumatic Brain Injury” (Darwinsh H, 2010) showed that mice with induced MTBI showed bio-markers for epigenetic changes 35 days after injury. Because similar studies involving neuro-chemical and axon changes after trauma in the human brain have shown, contrary to our expectation, that the changes are chronic and ongoing for up to seventeen years, it is likely that these epigenetic changes are going to be found to be chronic. The likelihood is that some of the adverse consequences associated with TBI are going to be transmittable to the next generations. These would include:
• Susceptibility to depression
• Susceptibility to anxiety.
• Perhaps decreased resistance to alzheimer’s and parksinson’s.
• Maladaption to stress and cortisol.
There should be a lot of work coming out on this in the next six months to one year. As if TBI victims didn’t have enough to worry about regarding recent research! The idea of trans generational tort damages, either suffering them as a plaintiff or paying for them as an insurance company, is for another day. Indeed.

Brain Injury and Fatigue

It is a very common complaint of victims of traumatic brain injury that since the injury they experience extreme bouts of fatigue. Symptoms of “fatigue” are often ignored or downplayed by doctors because  it is considered a “vague” symptom.  It is also a symptom that has not been specifically linked to any known mechanism or area of damage in of the brain.
Like many other aspects of brain injury, this symptom of fatigue is now being studied and explained in much greater detail than done before.  This is once again thanks to the sacrifice our soldiers have made in Iraq and Afghanistan and the Army researchers trying to help them.
The first thing we know about the creation of fatigue is that in functional MRI testing, TBI victims with frontal lobe injury, when asked to perform spelling or math problems, have a much higher rate of “brain recruitment”.  Brain recruitment means what part of the brain and how much of the brain is activated by doing a given task. By these recent studies we know that the person with the injured brain is forced to recruit a larger percentage of their brain to complete a certain task, whereas an uninjured person would be activating a much lower percentage of their brain.  The brain burns up about 30% of the bodies energy on a given day.  Thus, over-recruitment of the brain because of injury is literally fatiguing, since it is costing a much higher rate of energy to do things that previously cost the body much less energy.  It would be the same of putting 5 lb weights on each hand throughout the day.  It explains nicely why there is such widespread and debilitating fatigue with TBI survivors.
In another recent study (Vanzuiden M et al., 2012) soldiers were tested before and after deployment regarding reports of severe fatigue.  It was found that severe fatigue was associated with higher reactivity to IL-1 beta and it was found in higher levels in those with severe fatigue. TBI also plays a part in increasing what is known as pro-inflammatory cytokines in the blood for many months or years after injury.  This can explain the very high level of severe fatigue found in TBI survivors.  If a way can be found to decrease the reactivity to the immune system of the IL-1 beta, treatment can be found.

Brain Trauma and Alzheimer’s

Historically, there has been an association between brain injury and the later development of Alzheimer’s. The research regarding persons who have suffered repetitive trauma (boxers or football players) is clear – that repetitive trauma gives rise to the devastating condition known as Chronic Traumatic Encephalopathy, which is in effect, ultra early Alzheimer’s (U. EAD). In recent autopsies of deceased football players, pathologists encountered brains which appeared to be the brains of elderly people, when in fact the individuals were in their 30’s or 40’s. The repetitive trauma creates an accumulation of amyloid plaque and later “tangles” known as intracellular neurofibrillary threads (NFT) which are the hallmarks of this condition.


It was speculated, but not proven by any study, that a similar development could occur in the brain after a single traumatic brain injury in humans. Now, a recent study (Johnson VE et al. 2012) has shown that in those with a history of a single traumatic brain injury, there is long term pathology, involving a greater density of amyloid plaques and widespread NFT, in a third of the patients followed with survival of a year or more. The authors noted “This suggests that a single TBI induces long term neuropathologic changes akin to those found in neuro-degenerative disease.” Another study published in Brain Pathology (Chen X et al., 2009) followed 23 cases of post TBI survival patients for three years and found that even years later there was continued neuronal swelling in the axonal bulbs and axons. Strangely, the degree of axonal pathology three years later in survivors was higher than the cases in which death occurred after a much shorter duration, showing that axons continued to swell and disconnect over a protracted period of time. They noted “that the” at persistent nature of this pathology suggests that TBI can induce a progressive neuro-degenerative process.” The final mystery was that in this study, unlike some others, they did not find accumulation of amyloid plaque years later, even in the face of ongoing degeneration of brain tissue.

This news adds the our already staggering burden of future Alzheimer’s victims. To add thousands of additional individuals a year, because of TBI, to the pool of likely or even possible Alzheimer’s victims is distressing. We can only hope that our politicians and leaders in healthcare are taking notice of this potential time bomb. Add in injured soldiers and those unknowingly injured by repetitive trauma in a lifetime of sports and the future need for an Alzheimer’s cure becomes almost imperative.

New Study Sheds Light on TBI and Loss of Consciousness

An excellent study in the Journal of Neurotrauma (Browne KD et al. 2011) has shed light on another aspect of symptom onset – unconsciousness. Many insurance companies and some unread doctors, will insist that no brain injury can have occurred in an accident whereby the victim did not lose consciousness. They would likewise suggest that the primary method of brain injury in trauma, diffuse axonal injury, can likewise not occur unless the victim has a loss of consciousness. However, Dr. Browne and his colleagues using pigs, very rapidly rotated their heads in different directions without striking an object. This motion alone was found to cause diffuse axonal injury at levels consistent with mild traumatic brain injury. Interestingly, they found that rotation in the axial plane (being hit in the rear or front of a vehicle moving forward to back) produced unconsciousness in the pigs, while forces in which the head rotated along the croronal plane did not produce a sustained loss of consciousness. A week after the trauma the brains of the pigs were looked at and it was shown that both types of rotation produced similar and significant amount of DAI in both pigs, while the axial plane pigs brain stem showed signs of injury.


Therefore, it can now be said that loss of consciousness during an accident is a feature of the direction of movement of the head more than it is about the seriousness of the eventual brain injury found. Damage to the neurons of the brain can occur and do occur in the context of a mild traumatic brain injury with or without the unconsciousness that arises from damage or pressure to the brain stem. Loss of consciousness is not a equirement for brain injury nor for the presence or absence of DAI damage in the brain.


This study sheds light on why certain car accidents tend to knock out the occupants, while others do not. It is well known that angular rotational forces (e.g. a car hit from the side and not the rear) can injure the brain more readily.

TBI and Symptom Onset: What is Real?

For many years it has been medical gospel that symptoms of a tramatic brain injury will appear immediately after the impact and will thereafter decrease over the passage of time through recovery.  However, more research into the biological impact of TBI at the cellular level suggest that some of the damage to the brain tissue following trauma can continue for months and even years after the time of trauma.  There are also other factors which make this a formally “gospel” of symptom onset antiquated and untrue in many cases.


Canadian researchers (Doucher PA, et al. 2010) looked at how even initially mild axon damage tends to worsen in hours, days and even weeks after a head injury.  They found that within axon cells (white matter fibers that transmit information between lobes of the brain) trauma adversely affects the crucial pumping systems within the brain cell, throwing the healthy percentage of different chemicals in the cell out of whack, causing cell death.  In particular, the sodium, calcium, and potassium levels become excitotoxic, in which the electrical current in the cell is out of whack causing degeneration and death of the cell.


It is well known now that brain atrophy can appear even in the context of a mild traumatic brain injury.  Because of brain swelling, there are a few studies which indicate how much brain atrophy occurs within the first two months after injury, but one study suggest that most of the atrophy takes place during this time.  However, in cases of moderate and severe TBI, follow up studies have shown that the atrophy in the brain continues occurring at above normal aging rates, for a year and more.  Studies of the pathological chemical reactions following traumatic brain injury can continue to be found four years after the initial injury.  Using spectroscopy, which measures the exact correlation of chemical products within the brain, they have found that traumatized brains keep this adverse composition of brain matter and thus ongoing symptoms, for years following impact.


Finally, onset is often “delayed” because the victim, post injury, is doing nothing to tax the brain.  Two weeks in bed or off work or school, with no multi-tasking or complex social environment to deal with can give the illusion “that all is well.”  Even after returning to work or school, it can take months to fully realize or admit that “things are not right.”   Often friends and family gently point this out.


Victims should not be penalized by insurance companies for human nature – hoping they will be okay and going back to work.  When adverse psychological symptoms snowball and become worse.  This can also account for reports of significant impairment arising months after trauma


Overall, the research shows delayed biological events in the brain for months or a year post impact.  Treating doctors need to be aware of this.


In recent years a theory has been developed describing the brain as actively employing memory against incoming sensory data in order to avoid focusing on known factors and to try to predict instantaneously what is going to happen next. The brain has thus been called “a prediction computer.” It has also been called the “top-down prediction theory.” It rose through evolution and it allows our brains to function and not be overwhelmed by the amount of incoming sensory information.


A very interesting example of this can be shown on a YouTube clip (see Hollow Face Optical Illusion). There, we see something that is virtually never seen in the real world, namely a hollow face, which our brains “interpret” as a normal face, based upon 100% of our past experience. This shows how the “top-down” prediction model of how the brain works can actually alter our perceptions of what is really coming in through out sensory organs. Our brain is saying “this can’t possible be a hollow face” so it recreates what we see as a normal face. We have perception of an object, our brain’s instantaneous attempt to understand it, and to predict what it means. In the vast majority of instances, we sense things that we have previously sensed before. In that way, scientist have described the way the brain works as “saving band width” or not sending along sensory data that is or has been well predicted. Another example would be comparing your memories of a random day in the past thirty days with your memories of, say a vacation to Europe. Because your brain is less able to “predict” what is around the corner in a new and novel place, the experience is much better remembered than a day through the daily routine.

These theories and studies (Friston 2010; Bubic 2010; Keraga, 2007) also lead us into some interesting directions regarding rehabilitation of an injured brain and perhaps methods to utilize during our lives to strengthen the brain against the ravages of old age and dementia. Neuro-regeneration of brain cells is known to be enhanced by confronting “novelty.” It is obvious how this might occur – new connections and memories must be developed to accommodate confronting sensory data (visually, through sounds or taste) that is novel as unpredictable.


Thus, persons who are hardwired to seek novelty (neophilia) would tend to strengthen their brain over time when compared to individuals who stay within the confines of the very well known parameters of life. Likewise, it would seem that experiencing “avant garde” art and the added effort on the part of the brain, should be promotional of neuro-regeneration since, by its nature, it will confront the brain with new and unexpected sensory input, whether it be new modes of music, painting or even food. Studies have shown that the uncomfortable feeling people have when experiencing atonal or novel music is in part created by the brain sending out signals that it is confronting something unexpected. Further studies need to be done to confirm this connection.


The unexpected, the new, the novel, the challenging – all of these should be part of a regular diet for a healthy brain. Try to fool the prediction computer, shake it up a little bit.

Brain Rehabilitation Ideas

We know now that the brain is elastic throughout our entire lifetimes. That is, we are able to positively or negatively affect its structure by how we live. Illness and lack of cognitive stimulation result in a shrinking of key parts of the brain while physical exercise, cognitive stimulation, and healthy lifestyle tend to add brain mass.


We have been suggesting for clients at braininjury.com to engage in free methods of rehabilitation and to chart whether or not this program works for them. The program is simple:


1. Obtain a device capable of downloading and playing audiobooks with headphones.. Download several books to listen to but try to make selections that are not just easy listening. Remember that cognitive challenge is what we are looking for here.


2. Walk at least one hour per day while listening to your books through the headphones.


3. Take a different route each time if possible. Again, novelty and multi-tasking of the brain during physical exercise is what we are looking for.


We know walking itself over and above cardiovascular exercise, as well as exposure to novel situations promote and results in neuro-genesis.


We invite you to try this method of rehabilitation either acutely or in chronic situations ad would love to have you report back to braininjury.com on the outcomes.


We look forward to hearing from you.

The Second Brain in the Gut

In the last ten years a series of discoveries has changed our ideas about our mind/body connection. The evidence is building that one cannot distinguish the mind from the body, as previously thought. For example, with humans there is a second brain, complete with one hundred million neurons, which exists embedded in our intestines, known as the enteric nervous system. A bit of a surprise!


There is even a new field known as “Neuorgastroenterology” which studies the function and effects of the enteric nervous system. Does this second brain “help” us think? The early answer was no, but further studies have clouded the issue. Scientist have found that 90% of the information passing between the second brain through the first brain through the vagus nerve is information from the gut to the brain not the other way around. The enteric nervous systems uses 30 neuro-transmitters, just as the brain does. This explains why we feel emotional moods in the gut. Irritable bowel syndrome actually arises from too much serotonin in the gut. To complicate matters even further – serotonin is the primary neuro-transmitter involved in mood regulation (think prozac).


A recent study (Cryan JF, 2011) shows that the microbiota (actually foreign microorganisms that work in symbiosis, helping us digest our food) actually communicate with the brain and affect our behavior. Stress response, anxiety and depression have all been modulated by using mice bred not to accept certain bacteria in their gut.


This is only the beginning. This field has just begun to look into the full effects of the enteric nervous system on our lives. The effects of these discoveries on how we think about traumatic brain injury rehabilitation, mental illness rehabilitation and the pharmacology of mental illness will be far reaching. It is strange and humbling to think that billions of non-human bacteria are having a say in how we feel and act. For more information see the Second Brain by Michael Gershon.


End of Year Book Roundup

Here is a list some of the books that I have read this year, some outstanding some less so. In no particular order:


1. “The Root of Thought, Unlocking Glia the Brain Cell That Will Help Sharpen Our Wits, Heal Injury and Treat Brain Disease” by Andrew Koob – As you can tell from my earlier blogs, this book, one of the first describing the new found importance of Glia was very thought provoking to put it mildly.


2. “The Mind and The Brain” by Jeffrey M. Schwartz – This book describes the fascinating new research on neuroplasticity and has been the source of some of my earlier blogs.


3. “The Information” by James Gleick – This panoramic history of information and communication over the past 250 years was both interesting and relevant to many issues today ranging from computers to brain injury.


4. “Jeff in Venice, Death in the Varanasi” by Geoff Dyer – In this book the great British writer Dyer contrasts his experiences at the Venice’s Biennale, amid a decadent crush of social climbers, with transformative experiences in India.


5. “Dirt: The Erosions of Civilization” by David R. Montgomery – Here one learns that dirt is the vital skin on our earth that truly does decide the course of civilizations. Interestingly, Darwin, in one of his last books, described his theory of how earthworms created dirt. He was laughed at until proved correct seventy-five years later.


6. “State of Wonder” by Ann Patchett – A sprawling picaresque novel in which incredible medical discoveries are made in the Amazon jungle. It gives us insight into the sometimes non scientific ways in which science progresses or fails to progress.


7. “Zone One” by Colson Whitehead – This is a “literary zombie book” and it probably indeed has all of the problems that the terms conjures up.


8. “The Man in the Rockefeller Suit” by Mark Seal – This incredible true story almost defies belief. A young German boy, who learned English by imitating Thurston Howell III on Gilligan’s Island, comes to the United States and successfully impersonates a series of fictitious millionaires and finally successfully becomes a Rockefeller until arrested. This speaks to the primacy of our speech and diction in social interactions and prejudices.


9. “Uncertainty: Einstein, Heisenberg, Bohr and the Struggle for the Soul of Science” by David Lindley – This book describes the battle over the true nature of Quantum Mechanics and how Einstein ended up on the losing side of whether or not “entanglement” and other phenomenon really existed. Einstein never accepted Heisenberg’s “Uncertainty Principle” and was left behind by other physicist starting in 1925.


10. “How the Hippies Saved Physics” by David Kaiser – A historical follow-up to the earlier book, which shows howsome outcast scientist in the ‘60’s revived interests in “entanglement” and Bells theorem, aided strangely by defense department and CIA funding, resulting in breakthroughs that are now part of our everyday lives in internet security and communications.


11. “The Escape” by Adam T. Hirlwell – A comic British novel charting the comic activities of the main character as he comes to grips with his past, giving rise to stories of World War II, and whether he had a life well lived.


12. “Vanished Act: The Life and Art of Weldon Kees” by James Reidel – At mid-century Kees was a pivotal figure in modern art and poetry, but after jumping off the Golden Gate Bridge, his contributions were largely forgotten. An interesting journey into the cultural changes that predated the 1960’s.


13. “The Thousand Autumn’s of Jacob De Zoet” by David Mitchell – Mitchell, the author of the great book “The Cloud Atlas” (coming soon as a major motion picture) imagines life in Imperial Japan at a Dutch trading outpost and vividly creates the clash of cultures that this, the only trading outpost allowed in Japan, caused.


14. “A Ticket, A Pack and A Chart: Episodes from a Borderless Life” by Buz Donahoo – My good friend Buz Donahoo, a lifelong adventure guide, has put many of his interesting adventures into this all to short book. Worth reading.


15. “Joan Mitchell” by Patricia Albers – A biography of the one of the only woman painters allowed into abstract expressionist canon. Before becoming a painter, Mitchell was the youngest person to ever be published in Poetry Magazine.


16. “Busy Monsters” by William Giraldi – This high spirited comedy follows the epic failures of heartbroken protagonist Charlie Homar as he gets involved with fringe characters of all stripes after his girlfriend leaves him to capture a giant squid. A very funny book.


17. “Incognito: The Secret Lives of The Brain” by David Eagleman – Eagleman, now famous on television and radio, relays some of the interesting new breakthroughs in brain research. His method of describing some of the paradoxes in the brain is similar to the economics book “Freakonomics.”


18. “Remainder” by Tom McCarthy – This well reviewed British author’s book begins when the protagonist receives a huge legal settlement after being struck by a falling satellite. It gets even stranger after that. It does show some of the odd behaviors one can see after brain injury and how the actual “reality” that the victim sees can change dramatically as well.


19. “Inside Scientology: The Story of American’s Most Secretive Religion” by Janet Reitman – Scientology is much, much scarier than Tom Cruise jumping on a couch, it is almost like a paramilitary group that intimidates through litigation.


Insurance Company Blindness

There has been a great deal of advancement in the field of traumatic brain injury in the past twenty years, but unfortunately the insurance industry would just assume go back in time to the 1970’s and stay there.  This is because the recent advances in neuroscience and study of the brain have shown us that many of our earlier ideas about the brain were wrong.


Insurance companies continue to defend brain injury cases as they did twenty years ago by relying on medical ideas that are no longer valid – that someone must be rendered unconscious to suffer a traumatic brain injury, that a person with a normal CT or MRI cannot have a brain injury, that there is no mechanism by which brain injury can occur in the context of a mild traumatic brain injury.  How do they get away with treating claimants in this way, as if science had not progressed in the last twenty-years?  They do it, in part, by relying upon hand picked doctors to perform their compulsory medical exams (CME’s).  These examinations are part of every significant case that goes into litigation.  The court, the claimants and plaintiff’s attorney have no say over which doctor is chosen.  In most cases, even involving moderate or severe TBI, their doctors will find a way to blame the victim or ignore part of the medical evidence.  How is this done?


Hiring older or retired doctors who went to medical school and got their training before these discoveries were made.  They can then attempt to ignore more modern ideas unless plaintiff’s counsel forces them to do so;

Doctors rely upon “cherry picked” facts out of the case, ignoring data consistent with TBI and relying upon data of limited quality to make opinions.  An example of this, in one of my trials, was that a psychiatrist based his opinion that my client had a pre-existing personality disorder based upon a single sentence written in my client’s third grade school chart.  This was despite the fact that in 11th and 12th grade she was noted to be “well adjusted and well liked.”  This was despite ten independent witnesses that spoke to her ongoing character and work abilities.  Which is more reliable, a single sentence written thirty years ago, or the testimony of current friends and co-workers?

Another example is the issue of loss of consciousness.  When Plaintiff is claiming TBI and the medical records indicate that there was no loss of consciousness during or immediately after the accident, that fact is treated as the most important thing since the invention of the wheel by the defense doctors.  Yet, if the initial medical records show that the plaintiff was unconsciousness and had a diminished Glasgow Coma Scale (GCS), that fact will hardly ever make it into the doctors report.  Many of them feel that, while a lack of loss of consciousness can disprove a brain injury, a period of unconsciousness after an accident does not prove a brain injury.

Fortunately, a combination of the influx of our brave men and women from Iraq and Afghanistan, as well as new findings regarding NFL players, have sensitized both the public and younger doctors to the fragility of the brain.  What a wonderful and positive change it has been for our soldiers.  In the bad old days, and you might remember the movie Patton, when he slapped a “shell-shocked” soldier, there was no such thing as a mild or even moderate brain injury.   If you could walk and talk, you were not hurt.  There are many sad tales from these years of neglect, many lives in ruin through addiction, or criminal behavior following an injury.


However, the armed forces are currently doing a magnificent job studying mild traumatic brain injury, blast injuries and utilizing the latest tools such as DTI (Diffusion Tensor Imaging) to identify and rehabilitate traumatic brain injuries.  Likewise, the NFL players whose brain autopsies have come to light, have shed light on the terrifying damage done during football careers.


The “old” notions about brain injury will live on in TBI litigation, and because of this, attorneys involved in these cases need to be unceasing in their efforts to drag all insurance companies into the bright lights of the 21st Century, so the can see reality, clearly.


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