Association of Salivary MicroRNA Changes With Prolonged Concussion Symptoms
Association of Salivary MicroRNA Changes With Prolonged Concussion Symptoms
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DOI：
10.1001/jamapediatrics.2017.3884
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发表时间：
2018-01-01
期刊：
影响因子：
26.1
通讯作者：
Hicks, Steven D.
中科院分区：
文献类型：
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作者：
Johnson, Jeremiah J.;Loeffert, Andrea C.;Hicks, Steven D.
大约有三分之一的脑震荡儿童会出现长期的脑震荡症状。据我们所知，目前还没有客观或易于管理的测试来预测长期脑震荡症状。几项研究已经确定了创伤性脑损伤后被称为microRNA（miRNAs）的表观遗传分子的改变。没有研究检查是否miRNA表达可以检测长期脑震荡symptoms. ObjectiveTo评估唾液miRNA的有效性，以确定儿童脑震荡谁是长期symptoms.DESIGN的风险，设置，和参与者这项前瞻性队列研究在宾夕法尼亚州立大学医学中心观察了52例患者，年龄7至21岁，在最初的头部损伤14天内评估脑震荡，在第4周和第8周进行随访，发现所有患者都有脑震荡的临床诊断。主要结果和测量在所有患者的初始临床表现时测量唾液miRNA表达，运动性脑震荡评估工具（SCAT 3）症状评分≥ 5分的患者，结果在纳入的52例受试者中，22例（42%）为女性，平均（SD）年龄为14（3）岁。参与者被分为长期症状组（n = 30）和急性症状组（n = 22）。15个唾液miRNAs的浓度在偏最小二乘判别分析上空间区分了长期和急性症状组，并证明了与神经元调节通路的功能关系。5种miRNA（miR-320 c-1. miR-133a-5p。miR-769-5p，let-7a-3p。和miR-1307- 3 p）在逻辑回归上准确地鉴定了具有延长症状的患者（曲线下面积，0.856; 95%CI，0.822-0.890）。该准确性超过了儿童（曲线下面积，0.649; 95% CI，0.388-0.887）或父母（曲线下面积，0.562; 95% CI，0.219-0.734）SCAT 3评分的症状负担准确性。3种miRNAs的水平与损伤后4周的特定症状相关; miR-320 c-1与记忆困难相关（R，0.55;错误检测率，0.02），miR-S29与头痛相关（R，0.47;误检率，0.04），let-7 b-5 p与疲劳相关结论和相关性唾液miRNA水平可以识别脑震荡症状的持续时间和特征。这可以减少父母的焦虑，并通过提供脑震荡管理工具来改善护理。需要进一步验证这一方法。
IMPORTANCE Approximately one-third of children who experience a concussion develop prolonged concussion symptoms. To our knowledge, there are currently no objective or easily administered tests for predicting prolonged concussion symptoms. Several studies have identified alterations in epigenetic molecules known as microRNAs (miRNAs) following traumatic brain injury. No studies have examined whether miRNA expression can detect prolonged concussion symptoms.OBJECTIVE To evaluate the efficacy of salivary miRNAs for identifying children with concussion who are at risk for prolonged symptoms.DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study at the Penn State Medical Center observed 52 patients aged 7 to 21 years presenting for evaluation of concussion within 14 days of initial head injury, with follow-up at 4 and 8 weeks,EXPOSURES All patients had a clinical diagnosis of concussion.MAIN OUTCOMES AND MEASURES Salivary miRNA expression was measured at the time of initial clinical presentation in all patients, Patients with a Sport Concussion Assessment Tool (SCAT3) symptom score of 5 or greater on self-report or parent report 4 weeks after injury were designated as having prolonged symptoms.RESULTS Of the 52 included participants, 22 (42%) were female, and the mean (SD) age was 14 (3) years. Participants were split into the prolonged symptom group (n = 30) and acute symptom group (n = 22). Concentrations of 15 salivary miRNAs spatially differentiated prolonged and acute symptom groups on partial least squares discriminant analysis and demonstrated functional relationships with neuronal regulatory pathways. Levels of 5 miRNAs (miR-320c-1. miR-133a-5p. miR-769-5p, let-7a-3p. and miR-1307-3p) accurately identified patients with prolonged symptoms on logistic regression (area under the curve, 0.856; 95% CI, 0.822-0.890). This accuracy exceeded accuracy of symptom burden on child (area under the curve, 0.649; 95% CI, 0.388-0.887) or parent (area under the curve, 0.562; 95% CI, 0.219-0.734) SCAT3 score. Levels of 3 miRNAs were associated with specific symptoms 4 weeks after injury; miR-320c-1 was associated with memory difficulty (R, 0.55; false detection rate, 0,02), miR-S29 was associated with headaches (R, 0.47; false detection rate, 0.04), and let-7b-5p was associated with fatigue (R, 0.45; false detection rate, 0.04).CONCLUSIONS AND RELEVANCE Salivary miRNA levels may identify the duration and character of concussion symptoms. This could reduce parental anxiety and improve care by providing a tool for concussion management. Further validation of this approach is needed.