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

Background Sports-related head trauma is common but still there is no established laboratory test used in the diagnostics of minimal or mild traumatic brain injuries. Further the effects of recurrent head trauma on brain injury markers are unknown. The purpose of this study was to investigate the relationship between Olympic (amateur) boxing and cerebrospinal fluid (CSF) brain injury biomarkers. Methods The study was designed as a prospective cohort study. Thirty Olympic boxers with a minimum of 45 bouts and 25 non-boxing matched controls were included in the study. CSF samples were collected by lumbar puncture 1–6 days after a bout and after a rest period for at least 14 days. The controls were tested once. Biomarkers for acute and chronic brain injury were analysed. Results NFL (mean ± SD, 532±553 vs 135±51 ng/L p = 0.001), GFAP (496±238 vs 247±147 ng/L p<0.001), T-tau (58±26 vs 49±21 ng/L p<0.025) and S-100B (0.76±0.29 vs 0.60±0.23 ng/L p = 0.03) concentrations were significantly increased after boxing compared to controls. NFL (402±434 ng/L p = 0.004) and GFAP (369±113 ng/L p = 0.001) concentrations remained elevated after the rest period. Conclusion Increased CSF levels of T-tau, NFL, GFAP, and S-100B in >80% of the boxers demonstrate that both the acute and the cumulative effect of head trauma in Olympic boxing may induce CSF biomarker changes that suggest minor central nervous injuries. The lack of normalization of NFL and GFAP after the rest period in a subgroup of boxers may indicate ongoing degeneration. The recurrent head trauma in boxing may be associated with increased risk of chronic traumatic brain injury

REORGANIZING THE EMERGENCY DEPARTMENT TO REDUCE THROUGHPUT TIME BY INTRODUCING CROSS-FUNCTIONAL TEAMS

This paper reports the results from a test implementation at a Swedish emergency department, aiming at decreasing patient throughput time and time-to-doctor. The main approach was to introduce a team-based organization in combination with some integration of process-steps. The quantitative evaluation of patient data shows significant reduction in mean values of up to about 50 minutes for some patient groups, combined with an increased portion of the doctors’ time together with the patients

Reducing throughput time in a service organisation by introducing cross-functional teams

The purpose of this article is to investigate throughput time benefits when implementing cross-functional teams in a service organisation. The cross-functional teams, consisting of key human resources, are similarly designed to work cells within Cellular Manufacturing. Cellular manufacturing is an approach within manufacturing to achieve production flexibility and to shorten throughput time. This paper reports the results from implementing the cellular manufacturing principle at a Swedish emergency department, aiming at decreasing patient throughput time and time-to-doctor. The main approach was to introduce a team-based organisation, also involving some elimination of process steps. The quantitative evaluation of patient data shows significant reduction in mean values of up to about 40 minutes for some patient groups, combined with an increased portion of the doctors’ time together with the patients. The qualitative evaluation of the study show enhanced teamwork and communication, and also improved visibility and understanding of the work tasks of other team members

Increased CSF Levels of Phosphorylated Neurofilament Heavy Protein following Bout in Amateur Boxers

Introduction Diagnosis of mild TBI is hampered by the lack of imaging or biochemical measurements for identifying or quantifying mild TBI in a clinical setting. We have previously shown increased biomarker levels of protein reflecting axonal (neurofilament light protein and tau) and glial (GFAP and S-100B) damage in cerebrospinal fluid (CSF) after a boxing bout. The aims of this study were to find other biomarkers of mild TBI, which may help clinicians diagnose and monitor mild TBI, and to calculate the role of APOE ε4 allele genotype which has been associated with poor outcome after TBI. Materials and Methods Thirty amateur boxers with a minimum of 45 bouts and 25 non-boxing matched controls were included in a prospective cohort study. CSF and blood were collected at one occasion between 1 and 6 days after a bout, and after a rest period for at least 14 days (follow up). The controls were tested once. CSF levels of neurofilament heavy (pNFH), amyloid precursor proteins (sAPPα and sAPPβ), ApoE and ApoA1 were analyzed. In blood, plasma levels of Aβ42 and ApoE genotype were analyzed. Results CSF levels of pNFH were significantly increased between 1 and 6 days after boxing as compared with controls (p&lt;0.001). The concentrations decreased at follow up but were still significantly increased compared to controls (p = 0.018). CSF pNFH concentrations correlated with NFL (r = 0.57 after bout and 0.64 at follow up, p&lt;0.001). No significant change was found in the other biomarkers, as compared to controls. Boxers carrying the APOE ε4 allele had similar biomarker concentrations as non-carriers. Conclusions Subconcussive repetitive trauma in amateur boxing causes a mild TBI that may be diagnosed by CSF analysis of pNFH, even without unconsciousness or concussion symptoms. Possession of the APOE ε4 allele was not found to influence biomarker levels after acute TBI

Neurological Assessment and Its Relationship to CSF Biomarkers in Amateur Boxers

BACKGROUND: Mild traumatic brain injury (TBI) or concussion is common in many sports. Today, neuropsychological evaluation is recommended in the monitoring of a concussion and in return-to-play considerations. To investigate the sensitivity of neuropsychological assessment, we tested amateur boxers post bout and compared with controls. Further the relationship between neuropsychological test results and brain injury biomarkers in the cerebrospinal fluid (CSF) were investigated. METHOD: Thirty amateur boxers on high elite level with a minimum of 45 bouts and 25 non-boxing matched controls were included. Memory tests (Rey Osterrieth Complex Figure, Listening Span, Digit Span, Controlled Word Association Test, and computerized testing of episodic memory), tests of processing speed and executive functions (Trail Making, Reaction Time, and Finger Tapping) were performed and related to previously published CSF biomarker results for the axonal injury marker neurofilament light (NFL). RESULTS: The neurological assessment showed no significant differences between boxers and controls, although elevated CSF NFL, as a sign of axonal injury, was detected in about 80% of the boxers 1-6 days post bout. The investigation of the relationship between neuropsychological evaluation and CSF NFL concentrations revealed that boxers with persisting NFL concentration elevation after at least 14 days resting time post bout, had a significantly poorer performance on Trail Making A (p = 0.041) and Simple Reaction Time (p = 0.042) compared to other boxers. CONCLUSION: This is the first study showing traumatic axonal brain injury can be present without measureable cognitive impairment. The repetitive, subconcussive head trauma in amateur boxing causes axonal injury that can be detected with analysis of CSF NFL, but is not sufficient to produce impairment in memory tests, tests of processing speed, or executive functions. The association of prolonged CSF NFL increase in boxers with impairment of processing speed is an interesting observation, which needs to be verified in larger studies

Biomarker concentrations in cerebrospinal fluid and plasma.⁴

1<p>Test A: 1–6 days after last bout;</p>2<p>Test B: No boxing for at least 14 days.</p>3<p>According to pNFH, the result from one of the controls was destroyed.</p>4<p>Aβ <b>_1-42</b> was collected from plasma.</p

Investigation of relationship between neurological assessment and neurofilament light (NFL) in the cerebrospinal fluid (CSF).

<p>NFL in the cerebrospinal fluid has been analyzed in the same cohort of boxers and the results are previously published <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0099870#pone.0099870-Neselius1" target="_blank">[9]</a>. After a boxing bout, cerebrospinal fluid was collected at two occasions, first 1–6 days (test A) after bout and then after a rest period of at least 14 days (test B). 23 of 30 boxers had elevated concentrations of the axonal injury biomarker NFL at test A. At follow up, 4 of the boxers were lost, 12 of 26 (46%) boxers still hade elevated concentrations and these had significantly lesser performance on Trail Making A (p = 0.041) and Simple Reaction Time (p = 0.042) compared to the other boxers.</p>1<p><i>ROCF: Rey Osterrieth Complex Figure Test.</i></p>2<p><i>Vocabulary: 35 words were presented and for each word 0,1 or 2 points were assigned.</i></p>3<p><i>COWAT (Controlled Word Association Test): Participants were asked to generate as many words as possible that begin with the given letters F, A and S. Sixty seconds were allowed for each letter. One point per word was received.</i></p>4<p><i>Digit Span: Participants were presented with series of numbers, starting with three (for example 3–4–8). There were two series in each level and in total seven levels. The task was to immediately repeat the numbers back. When doing this successfully, the participants were given a longer serie of numbers.</i></p>5<p><i>Listening Span: A mixed lists of digits and letters were read aloud to the participants and they were asked to recall this list in correct numeric and alphabetic order.</i></p>6<p><i>Trail Making: In trail A the participant is instructed to trace a line that connects circled numbers in consecutive order. In trail B the task is to trace a line by alternating circled numbers and circled letters in consecutive order. Time is measured in seconds(s).</i></p>7<p><i>Reaction time: a) Simple reaction time: Participants were instructed to respond as quickly as possible whenever the circle appeared on the screen. Complex reaction time: Required participants to respond with right hand to the circle and left hand to the triangle. Difference = Complex−Simple reaction time.</i></p>8<p><i>Finger Tapping. In total five trials with 15 s rests between the trials. The participants were asked to press the space board with their index finger on the computer keyboard as many times as possible for 15 s, alternating dominate and non-dominant hand. The mean value was calculated.</i></p>9<p><i>Proportional values (range 0.04–0.96). The number of words in the auditory and visual conditions was 30 respectively. The correct recognition hit rates (HR) are presented.</i></p

Baseline details of boxers and controls.

1<p>One of the boxers was born without the smell sense and had been evaluated according this.</p>2<p>Neuropsychological intervention with 10 different symptoms of head and neck injury based on a previous study <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033606#pone.0033606-Jordan1" target="_blank">[29]</a>. Worsening of the number of symptoms the last 5–10 years was evaluated.</p

Cerebrospinal fluid concentrations of NFL in boxers test A correlate with Boxing Exposure.

<p>Boxing Exposure is a score that was constructed to calculate the total risk for traumatic brain injury before testing. It consists of three factors: 1. The total amount of bouts the last week before test A (1–3), 2. The boxers own grading of the bouts (easy (1), intermediate (2) or tough (3) and 3. The mean of the expert grading (3 boxing experts graded the boxers considering head trauma during total boxing career, 1 to 5). The results of these three factors were added in the boxing exposure score. Neurofilament light protein (NFL) analysed in cerebrospinal fluid (CSF) after bout (test A) correlated with Boxing Exposure, R = 0.396, p = 0.030.</p

Aβ1–42 shows a larger variation in the boxers vs controls.

<p>Cerebrospinal fluid (CSF) was collected from the controls once. The boxers were tested 1–6 days after a bout (A) and after a rest period without exposure to bouts or training with blows to head for at least 14 days (test B).</p