血浆生物标志物水平与其 CSF 浓度及职业运动员脑震荡次数和严重程度的关系。
Association of Plasma Biomarker Levels With Their CSF Concentration and the Number and Severity of Concussions in Professional Athletes.
机构信息
From the Institute of Neuroscience and Physiology (P.S., H.Z., J.S., N.J.A., M.S., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., H.Z., J.S., N.J.A., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Rehabilitation Medicine Department (P.S.), National Institutes of Health Clinical Center, Bethesda, MD; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, United Kingdom; UK Dementia Research Institute (H.Z.), London; Wallenberg Centre for Molecular and Translational Medicine (N.J.A., M.S.), University of Gothenburg, Sweden; King's College London (N.J.A.), Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), United Kingdom; Clinical Trials Unit (G.N.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; Division of Health (Y.T.), Medicine and Rehabilitation, Department of Health Science, Luleå University of Technology, Sweden; and Department of Neurology (R.D.-A.), University of Pennsylvania Perelman School of Medicine, Philadelphia.
出版信息
Neurology. 2022 Jul 26;99(4):e347-e354. doi: 10.1212/WNL.0000000000200615. Epub 2022 Jun 2.
BACKGROUND AND OBJECTIVES
To examine whether the brain biomarkers total-tau (T-tau), glial fibrillary acidic protein (GFAP), and β-amyloid (Aβ) 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 . 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, Aβ40, and Aβ42. Plasma T-tau, GFAP, Aβ40, and Aβ42 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, Aβ40, and Aβ42 concentrations measured in plasma did not correlate with the corresponding CSF concentrations, while there was a correlation between plasma and CSF levels of GFAP ( = 0.45, = 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, Aβ40, and Aβ42 measured in plasma did not relate to PCS severity. None of the markers measured in plasma correlated with number of concussions, except decreased Aβ42 in those with higher number of concussions ( = -0.40, = 0.04).
DISCUSSION
T-tau, GFAP, Aβ40, and Aβ42 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, Aβ40, and Aβ42 are not informative in the diagnosis of late effects of repetitive head injuries.
背景与目的
检测血浆中总 tau（T-tau）、神经胶质纤维酸性蛋白（GFAP）和β-淀粉样蛋白（Aβ）异构体 40 和 42 是否与职业运动员因重复性头部撞击（RHIs）导致的相应脑脊液（CSF）浓度、血脑屏障完整性和脑震荡后综合征（PCS）持续时间有关。
方法
在这项横断面研究中，因 RHIs 导致持续性 PCS（最近脑震荡后中位数 1.5 年）的职业运动员和未受伤的对照组接受了血液和 CSF 采样。PCS 的诊断基于. 运动员通过瑞典曲棍球联盟（SHL）和 SHL 医学委员会发布的关于该研究的信息传单招募。对照组通过瑞典哥德堡大学和萨尔格伦斯卡大学医院的传单招募。参与者在萨尔格伦斯卡大学医院接受腰椎穿刺和血液评估。主要观察指标为 RHIs 史和 PCS 严重程度（PCS >1 年与 PCS <1 年）与血浆和 CSF 中 T-tau、GFAP、Aβ40 和 Aβ42 浓度的关系。使用超敏检测技术定量检测血浆 T-tau、GFAP、Aβ40 和 Aβ42。
结果
共 47 名参与者（28 名运动员[中位数年龄 28 岁，范围 18-52 岁]因 RHIs 导致持续性 PCS，19 名对照组[中位数年龄 25 岁，范围 21-35 岁]）接受了配对的血液和 CSF 采样。血浆中 T-tau、Aβ40 和 Aβ42 的浓度与相应的 CSF 浓度没有相关性，而 GFAP 的血浆和 CSF 水平之间存在相关性（ = 0.45， = 0.020）。血浆 T-tau、GFAP 和 CSF 与血清白蛋白比值测量的血脑屏障完整性之间没有显著关系。血浆 T-tau、GFAP、Aβ40 和 Aβ42 与 PCS 严重程度无关。除了 Aβ42 在受检者中浓度降低（ = -0.40， = 0.04）与撞击次数较多有关外，血浆中测量的标志物与撞击次数均无相关性。
讨论
与 CSF 测量值相比，血浆中测量的 T-tau、GFAP、Aβ40 和 Aβ42 与 CSF 测量值不对应，并且可能对评估 RHIs 的迟发效应的诊断价值有限。
分类证据
这项研究提供了 III 级证据，表明在有脑震荡后症状的职业运动员中，血浆中 T-tau、GFAP、Aβ40 和 Aβ42 的浓度对于诊断重复性头部损伤的迟发效应并不具有信息性。
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