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- Shahim, Pashtun, 1984, et al.
(författare)
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Association of Plasma Biomarker Levels With Their CSF Concentration and the Number and Severity of Concussions in Professional Athletes
- 2022
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 99:4, s. E347-E354
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives To examine whether the brain biomarkers total-tau (T-tau), glial fibrillary acidic protein (GFAP), and beta-amyloid (A beta) isomers 40 and 42 in plasma relate to the corresponding concentrations in CSF, blood-brain barrier integrity, and duration of postconcussion syndrome (PCS) due to repetitive head impacts (RHIs) in professional athletes. Method In this cross-sectional study, professional athletes with persistent PCS due to RHI (median of 1.5 years after recent concussion) and uninjured controls were assessed with blood and CSF sampling. The diagnosis of PCS was based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). The athletes were enrolled through information flyers about the study sent to the Swedish Hockey League (SHL) and the SHL Medicine Committee. The controls were enrolled through flyers at University of Gothenburg and Sahlgrenska University Hospital, Sweden. The participants underwent lumbar puncture and blood assessment at Sahlgrenska University Hospital. The main outcome measures were history of RHI and PCS severity (PCS >1 year vs PCS <1 year) in relation to plasma and CSF concentrations of T-tau, GFAP, A beta 40, and A beta 42. Plasma T-tau, GFAP, A beta 40, and A beta 42 were quantified using an ultrasensitive assay technology. Results A total of 47 participants (28 athletes [median age 28 years, range 18-52] with persistent PCS due to RHI and 19 controls [median age, 25 years, range 21-35]) underwent paired blood and CSF sampling. T-tau, A beta 40, and A beta 42 concentrations measured in plasma did not correlate with the corresponding CSF concentrations, while there was a correlation between plasma and CSF levels of GFAP (r = 0.45, p = 0.020). There were no significant relationships between plasma T-tau, GFAP, and blood-brain barrier integrity as measured by the CSF:serum albumin ratio. T-tau, GFAP, A beta 40, and A beta 42 measured in plasma did not relate to PCS severity. None of the markers measured in plasma correlated with number of concussions, except decreased A beta 42 in those with higher number of concussions (r = -0.40, p = 0.04). Discussion T-tau, GFAP, A beta 40, and A beta 42 measured in plasma do not correspond to CSF measures and may have limited utility for the evaluation of the late effects of RHI, compared with when measured in CSF. Classification of Evidence This study provides Class III evidence that in professional athletes with postconcussion symptoms, plasma concentrations of T-tau, GFAP, A beta 40, and A beta 42 are not informative in the diagnosis of late effects of repetitive head injuries.
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| 2. |
- Shahim, Pashtun, 1984, et al.
(författare)
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Astroglial activation and altered amyloid metabolism in human repetitive concussion
- 2017
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Ingår i: Neurology. - : American Academy of Neurology. - 0028-3878 .- 1526-632X. ; 88:15, s. 1400-1407
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine whether postconcussion syndrome (PCS) due to repetitive concussive traumatic brain injury (rcTBI) is associated with CSF biomarker evidence of astroglial activation, amyloid deposition, and blood–brain barrier (BBB) impairment.Methods: A total of 47 participants (28 professional athletes with PCS and 19 controls) were assessed with lumbar puncture (median 1.5 years, range 0.25–12 years after last concussion), standard MRI of the brain, and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). The main outcome measures were CSF concentrations of astroglial activation markers (glial fibrillary acidic protein [GFAP] and YKL-40), markers reflecting amyloid precursor protein metabolism (Aβ38, Aβ40, Aβ42, sAPPα, and sAPPβ), and BBB function (CSF:serum albumin ratio).Results: Nine of the 28 athletes returned to play within a year, while 19 had persistent PCS >1 year. Athletes with PCS >1 year had higher RPQ scores and number of concussions than athletes with PCS <1 year. Median concentrations of GFAP and YKL-40 were higher in athletes with PCS >1 year compared with controls, although with an overlap between the groups. YKL-40 correlated with RPQ score and the lifetime number of concussions. Athletes with rcTBI had lower concentrations of Aβ40 and Aβ42 than controls. The CSF:serum albumin ratio was unaltered.Conclusions: This study suggests that PCS may be associated with biomarker evidence of astroglial activation and β-amyloid (Aβ) dysmetabolism in the brain. There was no clear evidence of Aβ deposition as Aβ40 and Aβ42 were reduced in parallel. The CSF:serum albumin ratio was unaltered, suggesting that the BBB is largely intact in PCS.
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| 3. |
- Shahim, Pashtun, et al.
(författare)
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Neurofilament light and tau as blood biomarkers for sports-related concussion
- 2018
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Ingår i: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 90:20, s. e1780-e1788
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Tidskriftsartikel (refereegranskat)abstract
- Objective To compare neurofilament light (NfL) and tau as blood-based biomarkers for acute sports-related concussion (SRC) and determine whether their concentrations at different time points after the injury are associated with prolonged time to return to play (RTP).Methods A total of 288 professional hockey players were followed longitudinally from September 1, 2012, to April 30, 2015. Data collection and biomarker analyses were conducted between 2015 and 2017. Associations were tested between blood concentrations of NfL and tau, and RTP time. Serum concentrations of S100B and neuron-specific enolase (NSE) were also measured for comparison.Results Of 288 players, 105 sustained an SRC. Of these, 87 underwent blood sampling 1, 12, 36, and 144 hours after SRC and at the RTP time point. Serum NfL concentrations 1, 12, 36, and 144 hours after SRC were related to prolonged RTP time, and could separate players with RTP >10 days from those with RTP ≤10 days (area under the receiver operating characteristic curve [AUROC] 0.82). Also, serum NfL 144 hours after SRC discriminated players who resigned from the game due to persistent postconcussion symptoms (PCS) from those who returned to play (AUROC 0.89). Plasma tau 1 hour after SRC was related to RTP but less strongly than NfL, while S100B and NSE showed no such associations.Conclusion Serum NfL outperformed tau, S100B, and NSE as a biomarker for SRC. From a clinical standpoint, serum NfL may be useful to identify individuals at risk of prolonged PCS, and may aid in biomarker-informed decisions with regard to when RTP should be considered.
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| 4. |
- Shahim, Pashtun, et al.
(författare)
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Neurofilament Light and Tau in the Aftermath of Human Repetitive Concussive Traumatic Brain Injury
- 2018
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Ingår i: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 80:15 Supplement
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To investigate whether professional athletes with post-concussion syndrome (PCS) due to repetitive concussive traumatic brain injury (rcTBI) have elevated cerebrospinal fluid (CSF) and plasma neurofilament light (NF-L) and tau as compared to controls, and whether elevated concentrations of these biomarkers are associated with persistent PCS.Background: Recently, CSF NF-L and tau have been reported to increase following acute repetitive head trauma. However, whether these biomarkers are elevated in CSF and plasma of athletes with PCS following rcTBI is unknown.Design/Methods: A total of 109 participants (31 professional athletes with PCS due to rcTBI, 48 concussed athletes without PCS, and 30 non-concussed athletic controls) were enrolled between September 2013 and September 2017. Athletes with PCS due to rcTBI also underwent paired CSF and plasma biomarker assessments, Rivermead Post-Concussion Symptoms Questionnaire (RPQ), and structural MRI of the brain (median, 1.5 years since last concussion).Results: Plasma NF-L concentrations were significantly increased in both the concussed and PCS group as compared with athletic controls. Among athletes with PCS, the highest concentrations of NF-L were observed in athletes with PCS > 1 year as compared to those with PCS < 1 year (area under the receiver-operating characteristics, 0.85). Furthermore, plasma concentrations of NF-L correlated with RPQ scores and lifetime number of concussions. In contrast, CSF and plasma concentrations of tau were not associated with injury severity or duration of PCS. Consistently, CSF NF-L correlated with corresponding plasma (r = 0.81, P < 0.001), while there was no significant correlation between CSF tau and corresponding plasma.Conclusions: Persistent PCS due to rcTBI is associated with axonal injury, which can be monitored by measuring NF-L in plasma samples months to year after last concussion. From a clinical standpoint, incorporation of plasma NF-L in the work-up may aid in distinguishing patients at increased risk of developing persistent PCS.Disclosure: Dr. Shahim has nothing to disclose. Dr. Tegner has nothing to disclose. Dr. Blennow has nothing to disclose. Dr. Zetterberg has nothing to disclose.
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| 5. |
- Shahim, Pashtun, 1984, et al.
(författare)
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Serum neurofilament light as a biomarker for mild traumatic brain injury in contact sports
- 2017
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Ingår i: Neurology. - : American Academy of Neurology. - 0028-3878 .- 1526-632X. ; 88:19, s. 1788-1794
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate whether the axonal protein neurofilament light (NFL) in serum is a sensitive biomarker to detect subtle brain injury or concussion in contact sports athletes.Methods: Two prospective cohort studies involving (1) 14 Swedish amateur boxers who underwent fluid biomarker assessments at 7–10 days after bout and after 3 months of rest from boxing and (2) 35 Swedish professional hockey players who underwent blood biomarker assessment at 1, 12, 36, and 144 hours after concussion and when the players returned to play were performed. Fourteen healthy nonathletic controls and 12 athletic controls were also enrolled. Serum NFL was measured using ultrasensitive single molecule array technology.Results: Serum NFL concentrations were increased in boxers 7–10 days after bout as compared to the levels after 3 months rest as well as compared with controls (p = 0.0007 and p < 0.0001, respectively). NFL decreased following 3 months of rest, but was still higher than in controls (p < 0.0001). Boxers who received many (>15) hits to the head or were groggy after bout had higher concentrations of serum NFL as compared to those who received fewer hits to the head (p = 0.0023). Serum NFL increased over time in hockey players, and the levels returned to normal at return to play. Importantly, serum NFL could separate players with rapidly resolving postconcussion symptoms (PCS) from those with prolonged PCS.Conclusions: The results from these 2 independent cohort studies suggest that serum NFL is a highly sensitive biomarker for concussion.
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