Sports Medicine Research: In the Lab & In the Field: Biomarkers in Olympic Boxing: Diagnosis and Effects of Repetitive Head Trauma (Sports Med Res)
Friday, June 1, 2012

Biomarkers in Olympic Boxing: Diagnosis and Effects of Repetitive Head Trauma

CSF-Biomarkers in Olympic boxing: Diagnosis and effects of repetitive head trauma

Neselius S., Brisby H., Theodorsson A., Blennow K., Zetterberg H,, Marcusson J. PLoS ONE. 2012; 7(4): 1-8.
It has been shown that there are deleterious acute and long-term effects (e.g., chronic traumatic brain injury) in the brain among boxing athletes. Currently, there are no objective measures sensitive enough to diagnosis a concussion or monitor the long-term effects from head impacts (e.g., neurofibrillary tangles, amyloid plaques). Therefore the purpose of this study was to evaluate the relation between cerebral spinal fluid biomarkers (an objective measure that marks the state of a biological process) and boxing exposure in elite Olympic boxers. The study included 30 Olympic boxers with a history of at least 45 bouts (only 26 boxers had complete data due to drop outs) and 25 healthy family or friend controls (non-boxers) matched on age. All participants filled out a questionnaire about medical history as well as any current head and neck signs and symptoms, medication, education, occupation, concussion history, as well as alcohol and drug usage. In addition the boxers reported data about their boxing career (e.g., number of knock outs, referee stoppages, record). With this information a boxing expert with no CSF biomarker knowledge graded the boxers into 1 of 5 boxing exposure categories, where 1 was a boxer with low risk to receive a head blow according to their reported skill and a boxing exposure category 5 was a boxer with the highest risk of receiving a blow to the head. After that, all of the participants had a neurological examination (e.g., concussion signs and symptoms, coordination, gait, cranial nerves, neurological status), magnetic resonance imaging (MRI), neuropsychological testing (e.g., long and short memory, mental speed, recollection), and finally a lumbar puncture. Lumbar punctures were collected twice for boxers (within 6 days of a bout and at least 14 days after a bout). The cerebral spinal fluid biomarkers included S-100b, T-tau, neurofilament light  (NFL), and glial fibrillary acidic protein (GFAP). The control subjects had 1 lumbar puncture. No difference were found between boxers and controls within their medical and social history. Only 1 boxer had current concussion signs and symptoms listed on the questionnaire. Both, boxers and control groups had no symptoms of concussion on their neurological exam, MRI, or neuropsychological examination. Boxers had significantly elevated concentrations of GFAP and NFL at both acute and long-term tests compared to controls. T-tau and S-100b were also significantly elevated in boxers compared to control but only during the acute test period.

Repetitive head trauma in boxing may be associated with increased risk of chronic traumatic brain injury. Analysis of biomarkers can assist in understanding the pathology associated, at a molecular level, with concussions. Furthermore, some biomarkers may be sensitive enough to detect subclinical brain responses to repetitive head impacts and could possibly be used to predict the risk of the patient having a prolong recovery or long-term effects. In this role, biomarkers may be able to prevent-long term effects if they can be eventually used to improve return to play guidelines. This data demonstrates that even though traditional objective and subjective data showed no concussion, the boxers had higher concentrations of the NFL, GFAP, S100-b, and T-tau biomarkers within 6 days of a bout, which indicates axonal and neuronal damage. Furthermore, the elevated NFL and GFAP, even after at least 14 days of no head impact exposures, may suggest ongoing degenerative changes. In addition, this suggests that boxers may need longer time off between bouts. Biomarkers may be used to evaluate recovery and useful in specific return to play guidelines, however, lumbar puncture is an evasive procedure. It would be interesting to see if these biomarkers are also elevated in the blood, which would be much easier to collect. Do you believe biomarkers would be a good tool in concussion diagnosis, return to play, and following long term recovery?

Written by: Jane McDevitt MS, ATC, CSCS
Reviewed by: Jeffrey Driban

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Neselius, S., Brisby, H., Theodorsson, A., Blennow, K., Zetterberg, H., & Marcusson, J. (2012). CSF-Biomarkers in Olympic Boxing: Diagnosis and Effects of Repetitive Head Trauma PLoS ONE, 7 (4) DOI: 10.1371/journal.pone.0033606

4 comments:

Natalie Reigh said...

I've always been confused as to the differences in protocols between standard sports and combative sports. I've had the opportunity to be around boxing and MMA athletes (not professionally as an ATC) and I can say that on a nightly basis, athletes would get knocked out from a punch or kick. Once they came around, if they felt ok they would just go back to practice. As someone with an athletic training background, this made me cringe, however that is how they have always done it. This is the complete opposite of the conservative protocol used in sports such as football, lacrosse, soccer, etc, where an athlete that loses consciousness is immediately pulled from play and monitored. What I don't understand is why we don't see combative sport athletes dying all the time from second impact syndrome, or other concussion related problems. While MMA is a relatively new sport, the disciplines that it utilizes (boxing, muay thai, jiu jitsu, wrestling, etc) have been around for a long time. It seems that based on the evidence in literature that encourages increasingly conservative treatment of concussions, that we should be seeing a lot more concussion related problems in combative sports. However it seems that you never hear about concussions in these sports. Is it just a lack of investigation?

Ryan Tierney said...

Posted on behalf of Ryan Tierney:

Natalie, you bring up many interesting points. One in particular is why don't we see more combative sport athletes dying from second impact syndrome (SIS) if they continue to participate immediately following an obvious concussion? Combative sport athletes frequently participate while concussed. How often does a punch to the head result in a boxer being dizzy or confused?...and the fight continues. This happens in other sports as well where athletes compete with signs and symptoms. So why only 8-10 SIS events annually? You would have to conclude that SIS is not simply a second concussion shortly after a first. As you note if that were the case there would be many more SIS cases. The problem is the pathomechanics of SIS and concussion are the same (i.e., head acceleration/deceleration events) but the injury to the brain is different. Why? Whats so special about those 8-10 players annually? Other than typically being young and playing while symptomatic, I don't think we know yet. Therefore i think it is best to be proactive in identifying the injury and conservative in the management. I am confident more research will emerge examining acute and longterm outcomes of combative sport participation as the sports continue to grow. (FYI - I recall an injury rate of 15 'severe' concussions/1,000AE for these sports).

Kerri Schmanek said...

I think the CSF-Biomarkers would be a good tool in concussion diagnosis and following long term recovery, but not for return to play guidelines. As mentioned in the article, would the boxers need a longer time between bouts before they returned to play? I don't think a biomarker would be the best tool for deciding if a boxer can return to the ring or not because it is their job to get hit in the head, therefore there will always be signs and symptoms of a concussion in these type of athletes. They can't afford to rest as much as an athlete in a non-combative sport can. Since they are a higher risk, the biomarker would be better for determining if there is a concussion or not compared to MRI's and the neuropsychological tests, and it can assess if there is potential for long term damage due to the fact that even after 14 days there were still traces of a concussion found by the biomarker indicating degenerative changes. I agree that this type of evaluation is evasive. If it can be collected in the blood that would be better, but even that is also evasive, just not as much as a lumbar puncture. Lastly, how much would it cost to have a procedure like this done, and who would administer it? Would this be able to be done on the sideline by an ATC, or does it have to be done by a physician in a doctors office?

Jane McDevitt said...

Keri-
One problem with these high risk athlete are defining if they developed a concussion. Biomarkers as you said would help with diagnosis; however, being medical professionals we can not let athletes continue to box if they have a concussion just because it is their job. We need to give them as much information as possible so they can decide if they want to continue. If we can tell them that their markers are indicating they still have a concussion they maybe more apt to sit out from contact practices. It costs about 300-400 dollars for an ELISA (a method to determine amount of biomarker per person) for 1 biomarker and after all the standards are put in they could run. You would also have to account for the cost of the blood collection like the needles and EDTA tubes. To take blood you must have your phlebotomy certification, and the equipment to store and run the samples. So at this time I am not even sure it could be done in a doctors office let alone an ATC lab. Maybe in the future it would be similar to an insulin prick test!

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