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Latest Medical Research about Brain Injury

Updated: 1 March 2017


LIFELONG IMPACT OF FOOTBALL

Individuals with a history of contact sports, especially football, were studied. It revealed a threshold dose-response relationship between the exposure to trauma and risk for later life cognitive impairment. The findings also showed a rise in abnormal levels of self reported executive function problems, depression, apathy, and behavioral disregulation.

TBI AS A CHRONIC DISEASE

Dr. Brent Mazel, who spearheaded the idea of TBI as a chronic disease, Dr. Randal Urban and others have found that TBI victims have yet another system in their bodies chronically altered by trauma. Here it was found that TBI victims had significantly lower circulating concentrations of many amino acids. These amino acids are essential for good health in many areas of the body. This abnormal metabolic condition and abnormal relationship between amino acids, hormones and cytokines is and should be studied further.

MRI BRAIN SCANS COMING TO EMERGENCY ROOMS?

There is currently no protocol to utilize MRI scanning at an emergency room with those suspected of having suffered TBI. The standard protocol is the quicker and cheaper CT scan. A new “brief MRI protocol” has been developed and in its initial test, in scans done within the first 48 hours after trauma, showed abnormalities in 57% of the patients. Nine of the nineteen suspected mild TBI patients with a negative CT had positive findings on the MRI. Most of the abnormalities on the MRI were noted on post contrast FLAIR.

The problem in proving objective damage in cases of mild TBI is illustrated here. The initial abnormalities are missed by the CT scan and six months or years after the event, the abnormalities can no longer be identified by radiologist. If they are seen, they are simply called “non-specific findings.” This has caused great distress in thousands of TBI victims in the last four years.

EVIDENCE OF MILD TBI INJURY

A study done in the Netherlands, a context in which litigation is non-existent and can not be a factor, showed that non hospitalized victims of mild traumatic brain injury had significant long term complaints. Six months after injury, 36% showed incomplete recovery, 25% returned to the outpatient neurology clinic within six months after injury. The findings ruled out anxiety and depression as cause of the continued difficulties.

ADHD AND TBI

A study involving over 6000 adolescents and young adults athletes of high school age showed that the athletes with pre-injury ADHD reported a higher rate of concussions than athletes without ADHD. Researchers were unable to determine whether the students were more susceptible to injury, have a lower threshold, or a different recovery rate than those without such a history.

Once again, this study confirms the well known observation that individuals who go into a TBI with preexisting difficulties such as ADHD, depression, anxiety, or any other brain dysfunction, have a worse outcome. This may be due to “glial activation” wherein these individual glial cells are already activated and are pathologically activated after a TBI. (See elsewhere on the site for more about glial activation).

BONE LOSS AND TBI

It has been well established that TBI itself has an impact on bone density loss. Injuries to the pituitary involving sex hormones, growth hormones and others have been shown to cause osteoporosis. Cushing's disease, the over production of cortisol, can also cause osteoporosis.

A recent study in mice showed 23 to 27% reduction in femur bone mass in animals with TBI twelve-weeks earlier. The findings indicate that TBI itself, with or without pituitary injury, can and does lead to bone loss. More research needs to be done.

TBI AND ALZHEIMER'S CONNECTED AGAIN

The accumulation of tau molecules are a feature of many neuro-degenerative disorders following TBI such as Alzheimer's and Parkinson's. Tau is also associated with the development of chronic CTE in football players. Scientist have now focused in on a molecule known as "Tau Oligoners" as the culprit in starting the brain pathologies in all of these groups. This molecule apparently initiates the protein misfolding that occurs as a result of many types of brain disease. Injection of this molecule into mice started a course of severe neuro-degeneration. However, once the administration was discontinued the mice went back to normal. It is reversible in this case.

There is also a possible non-intrusive biomarker for TBI and other neuro-degenerative conditions whereby the retina in the eye is examined to see if it has been invaded by tau oligoners. A test has not yet been developed.

 

 

THE EYE AND BRAIN SHRINKAGE

Another study, among many, showing observable objective changes in the brain after mild-TBI. Here brain volume in several parts of the brain, including the putamen, thalamus, amygdala and hippocampus seemed to be smaller than controls after the injury. They gradually resume most of their size after about a year, indicating recovery. (Zagorchev, L. et al. 2015).

Who is at Risk for Post Concussive Syndrome?

The study of those treated at an emergency room for mild TBI show the most commonly reported symptoms at first follow up where headache (27%), trouble falling asleep (18%), fatigue (17%), difficulty remembering (16%) and dizziness (16%). The following factors predict worse outcome:

  1. Consumption of alcohol prior to injury.
  2. The head injury resulted from a motor vehicle accident or fall.
  3. The presence of post injury headache.

Headache was more robustly associated with continued symptoms, more than loss of consciousness or alteration of consciousness or amnesia.

METHYLENE BLUE HELPS WITH TBI

Methylene blue, an old well used drug, has proved to be neuroprotective to the brains of rats after a concussion. It was protective against the size of lesions and the length of functional cognitive deficits. Clinically trials are under way.

DIFFUSION TENSOR IMAGING: A POWERFUL TOOL

The prognostic value of DTI/MR was shown in 61 patients with mild TBI who were scanned early after trauma. The results of the abnormalities in white matter shown by DTI correlated with the patients lowered performance on neuropsychological testing and contrasted sharply with controls. DTI continues to prove itself as a biomarker for TBI in the human brain.

A NEW TOOL

Microhemorrhages are one of the most common results of TBI, and with more powerful magnets and SWI/MR (Susceptibility Weighted Imaging), these micro hemorrhages can be identified. Taking it to another level, a program called SWIM (Susceptibility Weighted Imaging and Mapping) has been developed along with a Quantitative Susceptibility Mapping (QSM).

One of the problems with SWI is distinguishing between microhemorrhages and veins. These two programs substantially raise the accuracy of the identification of microhemorrhages. They can be done in a semi-automated manner with reasonable sensitivity and specificity. (Liu J. et al., 2015)

MORE EVIDENCE OF INJURY

An article in the American Journal of Neuroradiology looked into the use of DTI/MR to study chronic TBI patients. It was assumed that the iron remnants of blood, which is what is seen by the SWI, would or could dissipate over years. However, they found that these microhemorrhage sites arising in the brain after a severe trauma are "time independent," meaning that they do not fade over time. Another question answered was whether or not these tiny "tissue tears" in the brain are hemorrhagic or non hemorrhagic. Studies had determined the answer both ways. The study determined that most but not all microhemorrhages involve a hemorrhagic (blood orientated) aspect.

They also establish that traumatic microbleeds are:

  1. Located mainly in the frontal lobe and temporal lobe.
  2. The white matter of the superior frontal gyrus was most often affected.
  3. That the traumatic microbleeds were situated mainly at the gray matter-white matter border. These were further located more often next to the crowns rather than the base of the gyral stalks. Most were bilateral.
  4. Periventricular hyperintensities, (like spots close to the hollow ventricles in the center of our brain), are reported to be present in 74% of young normal persons and 89% of elderly normal persons. Therefore it is very important for your doctor and lawyer to distinguish these rather common abnormalities from those caused by trauma, particularly by location.
Unfortunately, a comment is made "diffuse axonal injury is usually related to general poor clinical status." This statement is based on a 1991 paper written prior to even the discovery that DIA occurred in mild TBI. (Scheid R. et al. 2003)

Protein Molecule Protects and Repairs After TBI

The molecule PIF (Pre-Implantation Factor) which was discovered and isolated by Dr. E. Barnea in studies at Yale University, has shown to be neuro-protective for prenatal and traumatic brain injury. The molecule, which was discovered being secreted by all mammalian embryos to merge the immune system of mother and child, has been found to perform extraordinarily well as a anti-inflammatory and as a molecule that may control adult stem cells in human tissue repair. Human trials on PIF begin in September 2014 and should have application in all autoimmune diseases, inflammatory diseases and traumatic injuries - an extraordinarily wide ranging and paradigm breaking type of discovery.

Cannabis Helps PTSD

There has been so much self medication of sufferers from PTSD with marijuana that this discovery probably comes as no small surprise. The discovery of humans having an entire system within the human body called the endocannabinoid system, some ten years ago, has given rise to many discoveries and many more are going to be forthcoming. It is no surprise that, since the human body is wired and has a built system responding to THC and similar molecules, that marijuana has and will continue to show great promise in medicating human disease and symptoms.

Loss of Sleep = Smaller Brain

A recent study confirmed the general notion that the cognitive abilities of a human are diminished during periods involving lack of normal sleep. It has long been known that a person with diminished sleep will score more poorly on academic and cognitive testing. A more recent finding gives an explanation for the need for sleep - that during sleep the brain and its surrounding tissues and fluids are cleaned and washed. It is therefore no surprise that a recent study (Sexton CE et al. 2014) showed that in humans with reduced sleep, the volume of their brain was found to be diminished.

The value of sleep and lack of sleep has traditionally been talked about as a relatively unimportant phenomenon that has no lasting or systemic damage to our bodies, but this attitude must and will soon change as the biological and objective damages of disruptive sleep become more and more evident.

Injury to the Cerebellum Equals Autism

The cerebellum, located in the very back of the human brain, has long been thought to mostly be involved with coordination and smooth movement of the human body. More recently, some connections to memory were surprisingly found. Now, a recent study (Wang SSH, et al. 2014) has shown that early injury to the cerebellum in human infants can lead to autism. The breakdown in normal brain development occurs when injury to the cerebellum puts into motion an abnormal course of development of a child's brain. It was found that infants with cerebellum injury have a 36 times greater likelihood of developing autism than an uninjured child. This, of course, would include prenatal injuries as well.

Using Light in the Brain

Scientist at Massachusetts Institute for Technology, in a study published in Nature, have been able to alter or remove memories in a mouse's brain using light beams. Negative memories of a mild shock were removed completely by this method. They also found that neurons in the hippocampus area of the brain, involving memory, can be altered to make a bad memory less negative. These breakthroughs will promise in future research involving the origins and treatment of anxiety and depression.

Mild Traumatic Brain Injury and Long Term Consequences

A 2011 study (Komrad, C et al.) followed 33 individuals who had sustained a mild TBI for an average of six years versus 33 healthy controlled subjects. Comprehensive testing was done to assess cognitive and emotional functioning. The results showed that mild TBI victims had significant impairments in cognitive domains compared to the healthy controlled subjects, with the effect being described from medium to large. They noted "MTBI may lead to lasting disruption of neurofrontal circuits not detectable by standard structural MRI and needs to be taken seriously in clinical and forensic evaluation."

Worsening Symptoms after MTBI

The conventional medical wisdom is that symptoms of a mild traumatic brain injury are at their worse at the time of the trauma and thereafter always get better, not worse. However, studies have shown (Bleiberg, J et al. 1997) that this is not always the case, when they compared normal volunteers with persons suffering from MTBI. The injured group showed erratic and inconsistent performances on follow up testing, with some subjects showing worsening performance across days. This and other studies are showing that this intolerance to worsening symptoms over time has no medical basis.

Inaccuracy of Mild TBI Diagnoses at ER

Every year, thousands of victims of TBI are failed to be diagnosed with a mild brain injury because of emergency room failure to diagnose. In the study entitled "Accuracy of Mild Traumatic Brain Injury Diagnoses" (Powell JM, et al. 2008) medical documents were reviewed from emergency room examinations resulting in a finding that 56% of those actually suffering from a mild TBI did not have a documented and related diagnoses in the ER records. The greatest agreement between the persons studied and the ER physicians who gave a positive mild TBI diagnoses was for loss of consciousness, with the greatest discrepancy for the symptom of confusion.

This failure and confusion does great harm to those patients who developed enduring or permanent symptoms from MTBI and because of this failure of a baseline diagnosis, follow up medical providers and especially insurance companies, will tend to disregard a legitimate diagnoses of MTBI.

The Spinal Cord and Vertigo

You usually would not consider damage or problems in the cervical spine to have anything to do with the symptom of dizziness or vertigo. However, research entitled "The Implications of Cervical Spine Degeneration and Traumatic Diseases in the Pathogenesis of Cervical Vertigo and Hearing Loss" (Cobzeanu, MD et al. 2009) showed that there are receptors located in the spinal disc and cervical spine muscles which affect blood flow in the arteries. This causes a disruption in ear blood flow which can bring on hearing loss, vertigo and ringing in the ears (Tinnitus). This could help explain some of the strange and unexplainable symptoms often reported by persons who have suffered a severe whiplash. ENTs need to become aware of this research as soon as possible.

Stress and Brain Development

Stress causes problems in all kinds of human body systems. Stress hormones have been linked to a reduction in brain neurogenesis, or memory cell replacement in the human brain, located in the hippocampus. (Schoenfeld, TJ 2012). Chronic stress can rise after a TBI injury. Other research has shown that when animals are lowered in the pecking order of their society, that there is a great increase in stress hormones. TBI victims who lose cognitive ability, suffer personality changes, and financial devastation, are commonly and suddenly thrown into a lower societal level. Thus, this additional stress worsens the conditions already present in the injured TBI victim. Studies have shown that TBI victims with more supportive families, obviously, do much better. Perhaps this alleviates some of the stress hormones.

Gene Expression Following TBI

Epigenetics and gene expression are cutting edge concepts which are making their way into the realm of traumatic brain injury. A study (Staffa, K et al. 2012) looked at twelve cases of severe brain injury resulting in death and analyzed whether or not the brain tissue had gene expression different than controls without TBI. They found that several substances were expressed in the cerebellum indicating that the cerebellum is an important target to study further regarding gene expression after TBI. This means that adverse changes in a parent with TBI can be passed to children. (for more see blog)

Blast Wave Hurt Axon

Further expiration of the effects of a blast wave on the brain continue to shed light. Mice, after being exposed to a blast, showed cognitive and behavioral changes. It was noted that it was a shortening of the axon initial segment (AIS) in the cortex and hippocampus. This increases both the threshold and the ability of the firing neurons to perform normally and supports the conclusion that exposure to a single blast can lead to mild traumatic brain injury (mTBI) with accompanying cognitive impairment and subcellular changes in the molecular organization of neurons.

Barbiturate Coma After Severe TBI

The idea of putting patients into a barbiturate coma after serious TBI in order to reduce the intracranial pressure (ICP) has been around for years. It has been controversial, and a new study (Majdan, M et al. 2012 ) showed that in five European treatment centers, while high dose barbiturates decrease ICP in 69% of patients, it also caused longer periods of pressure instability, which is exceedingly dangerous. The analysis showed no significant effect on outcome at any stage after injury. Probably not worth doing.

Gender Effect on TBI Outcome?

A study utilizing the Chinese head trauma data bank (Gao, GY 2012) studied over 7000 patients to determine whether or not there was a statistical difference between males and females suffering from traumatic brain injury regarding outcome. There was not. Mortality rates and unfavorable outcomes, showed no gender difference.

Hope for Vision Loss after TBI

A recent study (Sabel BA, et al. 2010) has shown that retinal or cerebral visual injury, long considered irreversible, can be restored with vision rehabilitation techniques. They propose the name "residual vision activation theory" and suggest it can be started at all ages and in all types of visual field impairment after stroke or TBI.

Conflicting Data on Stromal Cell Implantation

In the Journal of Neurotrauma (Bonilla C, et al. 2010) a study tested the intravenous administration of bone marrow stromal cells after traumatic brain injury in rats. After two months of administration the rats were no better at functional abilities. A study of their brains in comparison with the normal group showed no changes in the brains of the mice who received the intravenous stromal cells. However, the same group of investigators in 2009 had implanted the stromal cells, rather than have them administered through IV and found that the rats showed progressive functional recovery and signs of increased brain volume and neurogenesis in the autopsy brains of the rats. This is consistent with earlier studies (Zurita M. 2004) in which the therapeutic effect of transplanted bone marrow stromal cells showed clear and progressive functional recovery of treated animals compared with controls. In that case, new spinal cord tissue was grown bridging the traumatic injury and restoring function.

Surgeons in India have had success with transplantation of stem cells into humans suffering from severe traumatic brain injury and coma. More than one patient in a coma has recovered consciousness and speech after the operation.

In addition, several new drugs and treatments are on the horizon which will give rise to increased neurogenesis or regrowth of brain cells after injury or trauma. Pre-implantation factor (PIF) has been shown to be neuro-regenerative in mice and further studies following a successful toxicity trial will be under way at several universities.

Current Status of Stem Cells for Spinal Cord Regeneration

Many attempts in the last fifteen years have been made to find a method for enhancing spinal cord regeneration after injury. These include use of embryonic or adult stem cells, Schwann cells, genetically modified fibroblast, bone stromal cells, and olfactory ensheathing cells. Out of all the types of cells, a recent study (Sobani ZA, et al. 2010) showed that olfactory ensheathing cells seem to be the most promising, followed by bone marrow stromal cells. However, in the United States direct transplantion of these cells for spinal cord regeneration is not yet out of the experimental stage.

A human trial carried out in Australia had cultured olfactory ensheathing cells transplanted into the spinal cords of six patients with paraplegia. No improvement was noted. However, a quadriplegia patient who was operated on 13 days after a quadriplegia break at C4-5 using cultured bone marrow stomal cells showed gradual improvement in six months following the surgery.

Nerve Repair with Fat Derived Stem Cells Successful

Peripheral nerves (those outside the brain or spinal cord) can often cause ongoing and devastating nerve pain in the extremities. Micro surgery often cannot address all of the cell death involved in some of these conditions. However, combining nerve repair with placement of fat derived stem cells in the dorsal root ganglia showed nerve regeneration and neuro-protection with significant reduction of symptoms. (Reid AJ, et al. 2001).

Important Finding on Coma Decisions

The horrible choices as to the true nature of injury and patients with vegetative or minimally conscious states is well known. Investigators using resting state EEG (Fingelkurts AA, et al. 2011) show that (1) the EEGs for non survivors were significantly lower than for survivors; (2) there was a higher probability of mostly delta and slow beta waves during first assessment for patients with bad outcome (i.e. those who died within the first six months); (3) patients with a good outcome had higher probability of mostly fast-beta and alpha oscillations. Therefore resting state EEGs may have a potentially prognostic value with regards to outcome from VS or MCS. This will also be potentially helpful in medical-legal end of life decision making.

TRAUMATIC BRAIN INJURY AS CHRONIC DISEASE

A review of 25 years of treating survivors of brain injury in a university of Texas medical school study, shows that brain injury is a chronic ongoing process rather then a one time injury, as traditionally thought. The researchers hope to reclassify traumatic brain injury as a chronic disease, which will help researches with additional funding to investigate potential cures. They stress that neurological disorders can decrease life expectancy through sleep disorders, cardiac arrhythmia, or epilepsy. The disorders lead to gradual decline in cognitive functioning, a hosts of endocrine disorders, and psychiatric and psychological diseases.

TRAUMATIC BRAIN IN JURY COMMON AMONG HOMELESS

A study of more than 900 homeless men and women in Toronto showed that an astonishing 58% of the homeless men and 42% of the homeless women have a history of traumatic brain injury. For many people, the first instance of brain injury occur at a young age, suggesting that it could have set off a chain of events leading to homelessness. The study again highlights the seriousness of brain injury to a life as a successful human being.

SOLDIERS WITH BRAIN INJURY HAVE HIGHER EPILEPSY RISK DECADES LATER

New research in the publication Neurology, showed that 13% of post traumatic epilepsy reported in head-wounded veterans did not show up until more than 14 years after the brain injury. A study found that the types of seizure changed over time, often becoming more severe.

MILD HEAD INJURY INCREASED RISK OF SLEEP DISORDER

A study (Ayalon, L 2007) showed that as many as 40% to 65% of people with mild traumatic brain injury suffer from insomnia.. The head injury patients underwent numerous sleep studies and found that 15 of 42 patients or 36% had circadian rhythm sleep disorder (CRSD) it was noted that these disorders can lead to psychological and cognitive problems and can interfere with rehabilitation.

MORE EVIDENCE THAT PROGESTERONE AS TREATMENT FOR TRAUMATIC BRAIN INJURY

Researchers at Emory University (Stien, D.G. 2009) found that progesterone can protect damaged cells in the central and peripheral nervous system following traumatic brain injury. They found it can reduce swelling and the restriction of blood supply after an injury. It also protects neurons from dying after trauma. Because of its known safety, low costs and ready availability, progesterone should be widely used very soon.



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