PDF(Pubmed)
Abstract：
OBJECTIVE: Insomnia affects about one-third of patients with traumatic brain injury and is associated with worsened outcomes after injury. We hypothesized that higher levels of plasma neuroinflammation biomarkers at the time of TBI would be associated with worse 12-month insomnia trajectories.
METHODS: Participants were prospectively enrolled from 18 level-1 trauma centers participating in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study from February 26, 2014, to August 8, 2018. Plasma glial fibrillary acidic protein (GFAP), high-sensitivity C-reactive protein (hsCRP), S100b, neuron-specific enolase (NSE), and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) were collected on days 1 (D1) and 14 (D14) after TBI. The insomnia severity index was collected at 2 weeks, 3, 6, and 12 months postinjury. Participants were classified into insomnia trajectory classes based on a latent class model. We assessed the association of biomarkers with insomnia trajectories, controlling for medical and psychological comorbidities and demographics.
RESULTS: Two thousand twenty-two individuals with TBI were studied. Elevations in D1 hsCRP were associated with persistent insomnia (severe, odds ratio [OR] = 1.33 [1.11, 1.59], p = 0.002; mild, OR = 1.10 [1.02, 1.19], p = 0.011). Similarly, D14 hsCRP elevations were associated with persistent insomnia (severe, OR = 1.27 [1.02, 1.59], p = 0.03). Of interest, D1 GFAP was lower in persistent severe insomnia (median [Q1, Q3]: 154 [19, 445] pg/mL) compared with resolving mild (491 [154, 1,423], p < 0.001) and persistent mild (344 [79, 1,287], p < 0.001). D14 GFAP was similarly lower in persistent (11.8 [6.4, 19.4], p = 0.001) and resolving (13.9 [10.3, 20.7], p = 0.011) severe insomnia compared with resolving mild (20.6 [12.4, 39.6]. Accordingly, increases in D1 GFAP were associated with reduced likelihood of having persistent severe (OR = 0.76 [95% CI 0.63-0.92], p = 0.004) and persistent mild (OR = 0.88 [0.81, 0.96], p = 0.003) compared with mild resolving insomnia. No differences were found with other biomarkers.
CONCLUSIONS: Elevated plasma hsCRP and, surprisingly, lower GFAP were associated with adverse insomnia trajectories after TBI. Results support future prospective studies to examine their utility in guiding insomnia care after TBI. Further work is needed to explore potential mechanistic connections between GFAP levels and the adverse insomnia trajectories.
METHODS: Participants were prospectively enrolled from 18 level-1 trauma centers participating in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study from February 26, 2014, to August 8, 2018. Plasma glial fibrillary acidic protein (GFAP), high-sensitivity C-reactive protein (hsCRP), S100b, neuron-specific enolase (NSE), and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) were collected on days 1 (D1) and 14 (D14) after TBI. The insomnia severity index was collected at 2 weeks, 3, 6, and 12 months postinjury. Participants were classified into insomnia trajectory classes based on a latent class model. We assessed the association of biomarkers with insomnia trajectories, controlling for medical and psychological comorbidities and demographics.
RESULTS: Two thousand twenty-two individuals with TBI were studied. Elevations in D1 hsCRP were associated with persistent insomnia (severe, odds ratio [OR] = 1.33 [1.11, 1.59], p = 0.002; mild, OR = 1.10 [1.02, 1.19], p = 0.011). Similarly, D14 hsCRP elevations were associated with persistent insomnia (severe, OR = 1.27 [1.02, 1.59], p = 0.03). Of interest, D1 GFAP was lower in persistent severe insomnia (median [Q1, Q3]: 154 [19, 445] pg/mL) compared with resolving mild (491 [154, 1,423], p < 0.001) and persistent mild (344 [79, 1,287], p < 0.001). D14 GFAP was similarly lower in persistent (11.8 [6.4, 19.4], p = 0.001) and resolving (13.9 [10.3, 20.7], p = 0.011) severe insomnia compared with resolving mild (20.6 [12.4, 39.6]. Accordingly, increases in D1 GFAP were associated with reduced likelihood of having persistent severe (OR = 0.76 [95% CI 0.63-0.92], p = 0.004) and persistent mild (OR = 0.88 [0.81, 0.96], p = 0.003) compared with mild resolving insomnia. No differences were found with other biomarkers.
CONCLUSIONS: Elevated plasma hsCRP and, surprisingly, lower GFAP were associated with adverse insomnia trajectories after TBI. Results support future prospective studies to examine their utility in guiding insomnia care after TBI. Further work is needed to explore potential mechanistic connections between GFAP levels and the adverse insomnia trajectories.
摘要：
目的：失眠影响约三分之一的创伤性脑损伤患者，并与损伤后预后恶化相关。我们假设TBI时血浆神经炎症生物标志物水平较高与12个月失眠轨迹恶化相关。
方法：从2014年2月26日至2018年8月8日参加创伤性脑损伤转化研究和临床知识研究的18个一级创伤中心前瞻性招募参与者。血浆胶质纤维酸性蛋白（GFAP），高敏C反应蛋白（hsCRP），S100b,神经元特异性烯醇化酶（NSE），在TBI后第1天(D1)和第14天(D14)收集泛素羧基末端水解酶-L1(UCH-L1)。2周时收集失眠严重程度指数,受伤后3、6和12个月。根据潜在类别模型将参与者分为失眠轨迹类别。我们评估了生物标志物与失眠轨迹的关联，控制医疗和心理合并症和人口统计学。
结果：研究了两千两名TBI患者。D1hsCRP升高与持续性失眠相关(严重，赔率比[OR]=1.33[1.11，1.59]，p=0.002；轻度，OR=1.10[1.02，1.19]，p=0.011)。同样，D14hsCRP升高与持续性失眠（严重，OR=1.27[1.02，1.59]，p=0.03)。感兴趣的，D1GFAP在持续性重度失眠（中位数[Q1，Q3]：154[19，445]pg/mL）中低于缓解轻度失眠（491[154，1，423]，p<0.001）和持续性轻度（344[79，1,287]，p<0.001)。D14GFAP在持久性中同样较低(11.8[6.4，19.4]，p=0.001)和解析(13.9[10.3，20.7]，p=0.011）重度失眠与轻度失眠相比（20.6[12.4，39.6]。因此，D1GFAP的增加与持续严重的可能性降低相关(OR=0.76[95%CI0.63-0.92]，p=0.004）和持续性轻度（OR=0.88[0.81，0.96]，p=0.003）与轻度解决失眠相比。与其他生物标志物没有发现差异。
结论：血浆hsCRP升高，令人惊讶的是,GFAP降低与TBI后的不良失眠轨迹相关.结果支持未来的前瞻性研究，以检查其在TBI后指导失眠护理中的效用。需要进一步的工作来探索GFAP水平与不良失眠轨迹之间的潜在机械联系。
方法：从2014年2月26日至2018年8月8日参加创伤性脑损伤转化研究和临床知识研究的18个一级创伤中心前瞻性招募参与者。血浆胶质纤维酸性蛋白（GFAP），高敏C反应蛋白（hsCRP），S100b,神经元特异性烯醇化酶（NSE），在TBI后第1天(D1)和第14天(D14)收集泛素羧基末端水解酶-L1(UCH-L1)。2周时收集失眠严重程度指数,受伤后3、6和12个月。根据潜在类别模型将参与者分为失眠轨迹类别。我们评估了生物标志物与失眠轨迹的关联，控制医疗和心理合并症和人口统计学。
结果：研究了两千两名TBI患者。D1hsCRP升高与持续性失眠相关(严重，赔率比[OR]=1.33[1.11，1.59]，p=0.002；轻度，OR=1.10[1.02，1.19]，p=0.011)。同样，D14hsCRP升高与持续性失眠（严重，OR=1.27[1.02，1.59]，p=0.03)。感兴趣的，D1GFAP在持续性重度失眠（中位数[Q1，Q3]：154[19，445]pg/mL）中低于缓解轻度失眠（491[154，1，423]，p<0.001）和持续性轻度（344[79，1,287]，p<0.001)。D14GFAP在持久性中同样较低(11.8[6.4，19.4]，p=0.001)和解析(13.9[10.3，20.7]，p=0.011）重度失眠与轻度失眠相比（20.6[12.4，39.6]。因此，D1GFAP的增加与持续严重的可能性降低相关(OR=0.76[95%CI0.63-0.92]，p=0.004）和持续性轻度（OR=0.88[0.81，0.96]，p=0.003）与轻度解决失眠相比。与其他生物标志物没有发现差异。
结论：血浆hsCRP升高，令人惊讶的是,GFAP降低与TBI后的不良失眠轨迹相关.结果支持未来的前瞻性研究，以检查其在TBI后指导失眠护理中的效用。需要进一步的工作来探索GFAP水平与不良失眠轨迹之间的潜在机械联系。
