Monitoring concussion in a knocked-out boxer by CSF biomarker analysis.

Concussion is common in many sports, and the incidence is increasing. The medical consequences after a sport-related concussion have received increased attention in recent years since it is known that concussions cause axonal and glial damage, which disturbs the cerebral physiology and makes the brain more vulnerable for additional concussions. This study reports on a knocked-out amateur boxer in whom cerebrospinal fluid (CSF) neurofilament light (NFL) protein, reflecting axonal damage, was used to identify and monitor brain damage. CSF NFL was markedly increased during 36 weeks, suggesting that neuronal injury persists longer than expected after a concussion. CSF biomarker analysis may be valuable in the medical counselling of concussed athletes and in return-to-play considerations.

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.

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 sAPPß), ApoE and ApoA1 were analyzed. In blood, plasma levels of Aß42 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<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<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.

Olympic boxing is associated with elevated levels of the neuronal protein tau in plasma.

OBJECTIVES: The aim of this study was to investigate if olympic (amateur) boxing is associated with elevation of brain injury biomarkers in peripheral blood compared to controls. MATERIALS AND METHODS: Thirty olympic boxers competing in at least 47 bouts were compared to 25 controls. Blood was collected from the controls at one occasion and from the boxers within 1-6 days after a bout and after a rest period of at least 14 days. Tau concentration in plasma was determined using a novel single molecule ELISA assay and S-100B, glial fibrillary acidic protein, brain-derived neurotrophic factor and amyloid ß 1-42 were determined using standard immunoassays. RESULTS: None of the boxers had been knocked-out during the bout. Plasma-tau was significantly increased in the boxers after a bout compared to controls (mean ± SD, 2.46 ± 5.10 vs. 0.79 ± 0.961 ng L(-1), p = 0.038). The other brain injury markers did not differ between the groups. Plasma-tau decreased significantly in the boxers after a resting period compared to after a bout (p = 0.030). CONCLUSIONS: Olympic boxing is associated with elevation of tau in plasma. The repetitive minimal head injury in boxing may lead to axonal injuries that can be diagnosed with a blood test.

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.