Neurochemical Aftermath of Repetitive Mild Traumatic Brain Injury
Neurochemical Aftermath of Repetitive Mild Traumatic Brain Injury
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DOI：
10.1001/jamaneurol.2016.2038
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发表时间：
2016-11-01
期刊：
影响因子：
29
通讯作者：
Blennow, Kaj
中科院分区：
文献类型：
--
作者：
Shahim, Pashtun;Tegner, Yelverton;Blennow, Kaj
越来越多的证据表明，反复的轻度创伤性脑损伤（mTBI）事件可导致持续的长期衰弱症状，在某些情况下，可导致进行性神经退行性疾病，称为慢性创伤性脑病。然而，据我们所知，没有客观的工具来检查mTBI后持续的症状在多大程度上是由神经元损伤引起的。目的确定mTBI后持续的症状是否与脑损伤相关，如通过脑脊液生物化学标记物对轴突损伤和中枢神经系统损伤的其他方面进行评估。一项多中心横断面研究，涉及瑞典职业冰球运动员，他们反复患有mTBI，脑震荡后症状超过3个月，并符合根据精神障碍诊断和统计手册（第四版）的脑震荡后综合征（PCS）标准，与神经学上健康的对照个体相匹配。参与者于2014年1月至2016年2月期间入组。主要结果和指标脑脊液中神经丝轻蛋白、总tau蛋白、胶质细胞酸性蛋白、淀粉样蛋白β、磷酸化tau蛋白和神经颗粒蛋白浓度（16名PCS男性;中位年龄31岁;范围22-53岁; 15名对照个体[11名男性和4名女性];中位年龄25岁;范围21-35岁）进行了评估。在16名患有PCS的球员中，9名有PCS症状超过1年，而其余7名在一年内重返赛场。在PCS超过1年的运动员中，神经丝轻蛋白显著增加（中位数，410 pg/mL;范围，230-1440 pg/mL）与PCS在1年内消退的球员相比（中位数，210 pg/mL;范围，140-460 pg/mL）以及对照个体（中位数238 pg/mL，范围128-526 pg/mL;分别为P = 0.04和P = 0.02）。此外，神经丝轻蛋白浓度与Rivermead脑震荡后症状问卷评分和终生脑震荡事件相关（分别为rho = 0.58，P = 0.02和rho = 0.52，P = 0.04）。总体而言，与对照组相比，PCS患者的脑脊液淀粉样蛋白-β水平显著降低（中位数，1094 pg/mL;范围，845-1305 pg/mL; P = 0.05）。结论和相关性PCS患者的脑脊液神经丝轻蛋白增加和淀粉样蛋白β减少，提示轴突白色物质损伤和淀粉样蛋白沉积。这些生物标志物的测量可能是一个客观的工具，以评估与PCS的个人中枢神经系统损伤的程度，并区分个人谁是在发展慢性创伤性脑病的风险。
IMPORTANCE Evidence is accumulating that repeated mild traumatic brain injury (mTBI) incidents can lead to persistent, long-term debilitating symptoms and in some cases a progressive neurodegenerative condition referred to as chronic traumatic encephalopathy. However, to our knowledge, there are no objective tools to examine to which degree persistent symptoms after mTBI are caused by neuronal injury.OBJECTIVE To determine whether persistent symptoms after mTBI are associated with brain injury as evaluated by cerebrospinal fluid biochemical markers for axonal damage and other aspects of central nervous system injury.DESIGN, SETTINGS, AND PARTICIPANTS A multicenter cross-sectional study involving professional Swedish ice hockey players who have had repeated mTBI, had postconcussion symptoms for more than 3 months, and fulfilled the criteria for postconcussion syndrome (PCS) according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) matched with neurologically healthy control individuals. The participants were enrolled between January 2014 and February 2016. The players were also assessed with Rivermead Post Concussion Symptoms Questionnaire and magnetic resonance imaging.MAIN OUTCOMES AND MEASURES Neurofilament light protein, total tau, glial fibrillary acidic protein, amyloid beta, phosphorylated tau, and neurogranin concentrations in cerebrospinal fluid.RESULTS A total of 31 participants (16 men with PCS; median age, 31 years; range, 22-53 years; and 15 control individuals [11 men and 4 women]; median age, 25 years; range, 21-35 years) were assessed. Of 16 players with PCS, 9 had PCS symptoms for more than 1 year, while the remaining 7 returned to play within a year. Neurofilament light proteins were significantly increased in players with PCS for more than 1 year (median, 410 pg/mL; range, 230-1440 pg/mL) compared with players whose PCS resolved within 1 year (median, 210 pg/mL; range, 140-460 pg/mL) as well as control individuals (median 238 pg/mL, range 128-526 pg/mL; P =.04 and P =.02, respectively). Furthermore, neurofilament light protein concentrations correlated with Rivermead Post Concussion Symptoms Questionnaire scores and lifetime concussion events (rho = 0.58, P =.02 and rho = 0.52, P =.04, respectively). Overall, players with PCS had significantly lower cerebrospinal fluid amyloid-beta levels compared with control individuals (median, 1094 pg/mL; range, 845-1305 pg/mL; P =.05).CONCLUSIONS AND RELEVANCE Increased cerebrospinal fluid neurofilament light proteins and reduced amyloid beta were observed in patients with PCS, suggestive of axonal white matter injury and amyloid deposition. Measurement of these biomarkers may be an objective tool to assess the degree of central nervous system injury in individuals with PCS and to distinguish individuals who are at risk of developing chronic traumatic encephalopathy.