Article(id=1203057887435256051, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203057879566737430, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2023.02.0237, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1650556800000, receivedDateStr=2022-04-22, revisedDate=null, revisedDateStr=null, acceptedDate=1655827200000, acceptedDateStr=2022-06-22, onlineDate=1764760952099, onlineDateStr=2025-12-03, pubDate=1677513600000, pubDateStr=2023-02-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1764760952099, onlineIssueDateStr=2025-12-03, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1764760952099, creator=13701087609, updateTime=1764760952099, updator=13701087609, issue=Issue{id=1203057879566737430, tenantId=1146029695717560320, journalId=1189873630562394117, year='2023', volume='48', issue='2', pageStart='123', pageEnd='244', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1764760950222, creator=13701087609, updateTime=1764762101198, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1203062707223241334, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203057879566737430, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1203062707223241335, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203057879566737430, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=237, endPage=244, ext={EN=ArticleExt(id=1203057887884046604, articleId=1203057887435256051, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Advances in diagnosis and treatment of mild traumatic brain injury, columnId=1190243275882729994, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Review, runingTitle=null, highlight=null, articleAbstract=

Mild traumatic brain injury (mTBI) is common in modern warfare. If the wounded cannot receive early and effective diagnosis and treatment, long-term headaches, dizziness, insomnia, memory disorders, anxiety, depression and other symptoms will be easily left behind, which will seriously affect the quality of life and combat effectiveness of service members, and bring a huge burden on families and society. In recent years, the US Department of Defense has conducted a lot of research on the pathophysiological mechanism, examination, treatment and prognosis of mTBI, and formulated some guidelines and norms. This article reviews the progress in diagnosis and treatment of mTBI, facilitating the establishment of a standardized treatment system for mTBI.

, correspAuthors=Jian-Ning Zhang, authorNote=null, correspAuthorsNote=
E-mail:
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轻度创伤性脑损伤(mTBI)在现代战争中非常常见,如不能早期得到有效诊治,易遗留头痛、头晕、失眠、记忆力下降、焦虑、抑郁等多种症状,将严重影响官兵的生活质量和战斗力水平,为家庭和社会增加巨大负担。近年来,美军对mTBI的致伤机制、辅助检查、治疗手段、预后等进行了大量研究,并制定了相关的救治指南和规范。本文综述mTBI相关的诊断与治疗进展,以期为建立标准化的救治体系提供帮助。

, correspAuthors=张剑宁, authorNote=null, correspAuthorsNote=
张剑宁,E-mail:
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李彦腾,医学硕士,主要从事颅脑战创伤致伤机制及救治方面的研究

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李彦腾,医学硕士,主要从事颅脑战创伤致伤机制及救治方面的研究

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Chin Naut Med Hyperbar Med, 2021, 28(3): 271-275., articleTitle=Expert consensus on hyperbaric oxygen therapy for traumatic brain injury, refAbstract=null), Reference(id=1203057902694134550, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057887435256051, doi=null, pmid=null, pmcid=null, year=2021, volume=28, issue=3, pageStart=271, pageEnd=275, url=null, language=null, rfNumber=[72], rfOrder=84, authorNames=中国康复医学会高压氧康复专业委员会, 解放军总医院第六医学中心, journalName=中华航海医学与高气压医学杂志, refType=null, unstructuredReference=[中国康复医学会高压氧康复专业委员会, 解放军总医院第六医学中心.颅脑创伤高压氧治疗的专家共识[J]. 中华航海医学与高气压医学杂志, 2021, 28(3): 271-275.], articleTitle=颅脑创伤高压氧治疗的专家共识, refAbstract=null)], funds=[Fund(id=1203057892363563494, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057887435256051, awardId=AHJ14J001, language=EN, fundingSource=Scientific Research Projects of PLA Logistics(AHJ14J001), fundOrder=null, country=null), Fund(id=1203057892460032489, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057887435256051, awardId=AHJ14J001, language=CN, fundingSource=军队后勤科研计划项目(AHJ14J001), fundOrder=null, country=null), Fund(id=1203057892552307182, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057887435256051, awardId=BWS20B038, language=EN, fundingSource=GJB Project(BWS20B038), fundOrder=null, country=null), Fund(id=1203057892644581878, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057887435256051, awardId=BWS20B038, language=CN, fundingSource=国家军用标准项目(BWS20B038), fundOrder=null, country=null), Fund(id=1203057892757828090, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057887435256051, awardId=LB20191A010010, language=EN, fundingSource=Equipment Comprehesive Research Project of the Joint Service of PLA(LB20191A010010), fundOrder=null, country=null), Fund(id=1203057892862685694, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057887435256051, awardId=LB20191A010010, language=CN, fundingSource=联勤保障部队装备综合研究项目(LB20191A010010), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1203057888521580855, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057887435256051, xref=null, ext=[AuthorCompanyExt(id=1203057888529969465, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057887435256051, companyId=1203057888521580855, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Neurosurgery, the First Medical Center of PLA General Hospital, Beijing 100853, China), AuthorCompanyExt(id=1203057888546746686, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057887435256051, companyId=1203057888521580855, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=解放军总医院第一医学中心神经外科医学部,北京 100853)])], figs=[ArticleFig(id=1203057891742806469, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057887435256051, language=EN, label=Tab. 1, caption=

Criteria for judging the degree of TBI from US Department of Defense

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项目轻型TBI中型TBI重型TBI
CT或MRI检查正常正常或异常正常或异常
意识丧失(h)<0.50.5~24>24
意识水平下降(h)<24>24>24
外伤性遗忘(d)0~11~7>7
GCS评分(最好为伤后24 h内)13~159~123~8
), ArticleFig(id=1203057891822498251, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057887435256051, language=CN, label=表1, caption=

美军的TBI损伤程度判定标准

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项目轻型TBI中型TBI重型TBI
CT或MRI检查正常正常或异常正常或异常
意识丧失(h)<0.50.5~24>24
意识水平下降(h)<24>24>24
外伤性遗忘(d)0~11~7>7
GCS评分(最好为伤后24 h内)13~159~123~8
), ArticleFig(id=1203057891914772944, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057887435256051, language=EN, label=Tab. 2, caption=

The related symptoms of mTBI

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项目相关临床表现
躯体症状头痛,头晕和平衡障碍,疲乏,恶心、呕吐,视觉异常,听力下降或耳鸣,嗅觉异常,感觉麻木,食欲不振
认知改变记忆力下降,反应迟钝,注意力难以集中
行为情感异常睡眠紊乱或嗜睡,易怒,焦虑,抑郁,性格改变
), ArticleFig(id=1203057892002853330, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057887435256051, language=CN, label=表2, caption=

mTBI相关的临床表现

, figureFileSmall=null, figureFileBig=null, tableContent=
项目相关临床表现
躯体症状头痛,头晕和平衡障碍,疲乏,恶心、呕吐,视觉异常,听力下降或耳鸣,嗅觉异常,感觉麻木,食欲不振
认知改变记忆力下降,反应迟钝,注意力难以集中
行为情感异常睡眠紊乱或嗜睡,易怒,焦虑,抑郁,性格改变
), ArticleFig(id=1203057892128682457, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057887435256051, language=EN, label=Tab. 3, caption=

Biomarkers of mTBI and their clinical significance

, figureFileSmall=null, figureFileBig=null, tableContent=
生物标志物[44-51]临床意义
脑组织损伤类
 中枢神经特异蛋白(S100β)存在于星形胶质细胞,颅脑损伤后血清S100β蛋白水平与预后不良显著相关,血清S100β >2 μg/L预测mTBI的敏感度为99.63%
 神经元特异烯醇化酶(NSE)反映神经元的损伤,血浆NSE水平与TBI患者损伤的严重程度显著相关,并与格拉斯哥昏迷评分呈负相关
 胶质纤维酸性蛋白(GFAP)反映星形胶质细胞损伤,仅在中枢神经系统中发现,判断TBI具有较高特异性,并能很好地预测病情,分辨损伤的严重程度
 Tau蛋白存在于神经元的胞核,血清Tau蛋白可判断TBI的预后,预测不良预后的敏感度为88%,特异度为94%
 髓鞘碱性蛋白(MBP)存在于神经元轴突髓鞘,血清MBP浓度对TBI的预后有一定预测作用
 泛素羧基末端水解酶L1(UCH-L1)反映神经元损伤,急性期血清UCH-L1水平升高与脑损伤严重程度相关,并可预测患者损伤后6个月的死亡风险增加
炎症反应类
 白细胞介素-6(IL-6)在中枢神经系统炎症的发生过程中,激活的小胶质细胞和星形胶质细胞可促进IL-6的产生。血清IL-6水平与患者 TBI 后颅内压的升高相关,可作为预测TBI合并颅内压升高的有效生物标志物
 IL-10是一种具有强大抗炎特性和免疫调节功能的细胞因子。血清IL-10水平升高与TBI严重程度和病死率相关
新兴TBI标志物
 线粒体DNA线粒体DNA拷贝数可早期判断TBI神经功能损伤程度,为及时采取干预措施提供帮助,是改善急性TBI伤员预后的潜在治疗靶点
 游离DNA血浆游离DNA水平与TBI患者的严重程度相关,同时对TBI后病死率的预测价值很高
 循环microRNA包括miR-16、miR-92a、miR-93、miR-191、miR-499、miR-765等,血清miRNA是判断TBI严重程度分级和治疗效果的良好指标
 脑源性微囊泡与脑损伤程度和认知功能变化有关
), ArticleFig(id=1203057892237734365, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057887435256051, language=CN, label=表3, caption=

mTBI相关的生物标志物及其临床意义

, figureFileSmall=null, figureFileBig=null, tableContent=
生物标志物[44-51]临床意义
脑组织损伤类
 中枢神经特异蛋白(S100β)存在于星形胶质细胞,颅脑损伤后血清S100β蛋白水平与预后不良显著相关,血清S100β >2 μg/L预测mTBI的敏感度为99.63%
 神经元特异烯醇化酶(NSE)反映神经元的损伤,血浆NSE水平与TBI患者损伤的严重程度显著相关,并与格拉斯哥昏迷评分呈负相关
 胶质纤维酸性蛋白(GFAP)反映星形胶质细胞损伤,仅在中枢神经系统中发现,判断TBI具有较高特异性,并能很好地预测病情,分辨损伤的严重程度
 Tau蛋白存在于神经元的胞核,血清Tau蛋白可判断TBI的预后,预测不良预后的敏感度为88%,特异度为94%
 髓鞘碱性蛋白(MBP)存在于神经元轴突髓鞘,血清MBP浓度对TBI的预后有一定预测作用
 泛素羧基末端水解酶L1(UCH-L1)反映神经元损伤,急性期血清UCH-L1水平升高与脑损伤严重程度相关,并可预测患者损伤后6个月的死亡风险增加
炎症反应类
 白细胞介素-6(IL-6)在中枢神经系统炎症的发生过程中,激活的小胶质细胞和星形胶质细胞可促进IL-6的产生。血清IL-6水平与患者 TBI 后颅内压的升高相关,可作为预测TBI合并颅内压升高的有效生物标志物
 IL-10是一种具有强大抗炎特性和免疫调节功能的细胞因子。血清IL-10水平升高与TBI严重程度和病死率相关
新兴TBI标志物
 线粒体DNA线粒体DNA拷贝数可早期判断TBI神经功能损伤程度,为及时采取干预措施提供帮助,是改善急性TBI伤员预后的潜在治疗靶点
 游离DNA血浆游离DNA水平与TBI患者的严重程度相关,同时对TBI后病死率的预测价值很高
 循环microRNA包括miR-16、miR-92a、miR-93、miR-191、miR-499、miR-765等,血清miRNA是判断TBI严重程度分级和治疗效果的良好指标
 脑源性微囊泡与脑损伤程度和认知功能变化有关
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轻度创伤性脑损伤的诊断与治疗研究进展
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李彦腾 , 程岗 , 张剑宁 *
解放军医学杂志 | 综述 2023,48(2): 237-244
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解放军医学杂志 | 综述 2023, 48(2): 237-244
轻度创伤性脑损伤的诊断与治疗研究进展
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李彦腾, 程岗, 张剑宁*
作者信息
  • 解放军总医院第一医学中心神经外科医学部,北京 100853
  • 李彦腾,医学硕士,主要从事颅脑战创伤致伤机制及救治方面的研究

通讯作者:

张剑宁,E-mail:
Advances in diagnosis and treatment of mild traumatic brain injury
Yan-Teng Li, Gang Cheng, Jian-Ning Zhang*
Affiliations
  • Department of Neurosurgery, the First Medical Center of PLA General Hospital, Beijing 100853, China
出版时间: 2023-02-28 doi: 10.11855/j.issn.0577-7402.2023.02.0237
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轻度创伤性脑损伤(mTBI)在现代战争中非常常见,如不能早期得到有效诊治,易遗留头痛、头晕、失眠、记忆力下降、焦虑、抑郁等多种症状,将严重影响官兵的生活质量和战斗力水平,为家庭和社会增加巨大负担。近年来,美军对mTBI的致伤机制、辅助检查、治疗手段、预后等进行了大量研究,并制定了相关的救治指南和规范。本文综述mTBI相关的诊断与治疗进展,以期为建立标准化的救治体系提供帮助。

创伤性脑损伤  /  磁共振成像  /  生物标志物  /  治疗

Mild traumatic brain injury (mTBI) is common in modern warfare. If the wounded cannot receive early and effective diagnosis and treatment, long-term headaches, dizziness, insomnia, memory disorders, anxiety, depression and other symptoms will be easily left behind, which will seriously affect the quality of life and combat effectiveness of service members, and bring a huge burden on families and society. In recent years, the US Department of Defense has conducted a lot of research on the pathophysiological mechanism, examination, treatment and prognosis of mTBI, and formulated some guidelines and norms. This article reviews the progress in diagnosis and treatment of mTBI, facilitating the establishment of a standardized treatment system for mTBI.

traumatic brain injury  /  magnetic resonance imaging  /  biomarkers  /  therapy
李彦腾, 程岗, 张剑宁. 轻度创伤性脑损伤的诊断与治疗研究进展. 解放军医学杂志, 2023 , 48 (2) : 237 -244 . DOI: 10.11855/j.issn.0577-7402.2023.02.0237
Yan-Teng Li, Gang Cheng, Jian-Ning Zhang. Advances in diagnosis and treatment of mild traumatic brain injury[J]. Medical Journal of Chinese People’s Liberation Army, 2023 , 48 (2) : 237 -244 . DOI: 10.11855/j.issn.0577-7402.2023.02.0237
无论和平时期还是战争时期,创伤性脑损伤(traumatic brain injury,TBI)都是军队重要的医疗卫生问题,即使轻度创伤性脑损伤(mild TBI,mTBI)也会降低伤员的战斗力,增加其发生其他损伤的风险[1]。部分mTBI伤员还会遗留持续性的身体或精神方面的问题,如头痛、头晕、失眠、记忆力下降、焦虑、抑郁等多种症状,严重影响官兵的生活质量和战斗力水平[2]。然而,mTBI因其外在症状轻微,易被误诊或漏诊而错失有效救治的最佳时机,成为削弱战斗力和影响官兵身心健康的重要因素。
军人的TBI发病率高于平民,在战时更是显著升高。TBI的致伤因素主要包括爆炸、枪弹伤、交通事故、跌倒、坠落、暴力击打等[3]。在近年的伊拉克和阿富汗战争及俄乌战争中,多种高爆、高能武器和简易爆炸装置的广泛应用,加之单兵防护服性能的大幅提升,导致TBI比例激增,成为现代战争的“标志性损伤”。据美国国防和退伍军人脑损伤中心统计,2000-2016年,美军共报告TBI 35万例,其中80%(约29万例)是mTBI[4];mTBI的主要致伤因素是爆炸产生的冲击波[5]。在特殊环境(如建筑物、舰船、车辆内部或水下)发生的爆炸,冲击波的杀伤效果可增强数倍甚至数十倍[6-7]。脑爆炸伤(blast-related TBI,bTBI)在颅脑战创伤中的占比已从第一次世界大战时的不足20%增加至近年的80%以上[8]
值得注意的是,参战人员在发生mTBI后,遗留长期症状的比例较高。平民mTBI患者中只有3%~5%发生头痛、头晕、失眠、焦虑、抑郁、记忆力和定向力障碍等长期症状,被称为“不幸的少数”[9];而军人mTBI中这一比例可达20%~48%[10-11],给家庭和社会带来沉重负担。美国军人TBI治疗相关的经济成本呈指数增长,至2010年已达6.46亿美元,其中30%~45%用于mTBI[12]。虽然mTBI早期救治的费用一般低于中重型TBI,但此类伤员数量更多,且往往需要长期的康复治疗,对社会、家庭和个人的长远影响比中重型TBI更大[11,13]。因此,mTBI日益受到美国国防部、退伍军人事务部和国会的关注,成为美军卫生勤务的重点任务。
mTBI主要是突发的外力作用造成颅腔内脑组织发生快速的加速或减速导致旋转或线性剪切应力的结果[14]。由于组织的黏滞系数和密度不同,额叶和颞叶的灰质交界处是更易发生损伤的部位[15]。轴突遭受剪切应力后发生挫伤或断裂,损伤广泛时称为弥漫性轴索损伤,是mTBI导致认知功能障碍的主要原因[16]。mTBI相关的脑代谢和神经网络连接紊乱可能与离子水平、代谢和生理过程的变化等复杂级联有关。在剪切力的瞬时牵拉作用下,神经元胞体和轴突的细胞膜完整性遭到破坏,膜上的离子通道功能紊乱,离子不受控制地进入细胞内;之后,引发神经递质大量释放,特别是兴奋性氨基酸(如谷氨酸和天冬氨酸),导致神经元内离子稳态进一步失衡;而后引发线粒体功能障碍,导致细胞器功能失常,细胞发生坏死或凋亡。同时,神经胶质细胞受到损伤刺激后,释放氧自由基、氮自由基、炎性细胞因子等,进一步加重了神经元损伤[17-18]。如果这种紊乱的微环境持续存在,将会引起脑组织内慢性低水平的炎症反应,造成神经功能的持续障碍[19]。此外,颅内微血管发生损伤或痉挛,可导致脑组织缺血、缺氧,线粒体功能障碍,也是发生继发性损伤的一种重要机制[20]
对于bTBI,按致伤因素可分为四级:初级损伤是bTBI的特征性损伤方式,与爆炸产生的冲击波有关,二级、三级、四级分别是由弹片或二次破片、身体跌落碰撞或爆炸产生的高温、火球、有毒气体等引起。初级损伤由于损伤机制的特殊性,是当前研究的热门领域。值得注意的是,77%的TBI士兵在受伤时都戴有头盔,而现有的头盔多以弹片或撞击为防护目标,对冲击波的防护效果欠佳[21-22]。综合以往尸体、动物和人工模型的研究结果,TBI发生的生物力学机制主要有以下几种假说:(1)颅骨骨孔假说。冲击波通过听道、鼻窦、眼眶等骨孔进入颅腔,引起颅内压升高[23]。(2)颅骨直接传播假说。冲击波能够直接穿过颅骨进入颅内,进而对颅内压产生影响[24]。(3)颅骨变形假说。该假说不同于颅骨直接传播假说,认为颅骨在冲击波作用下产生变形和振动,进而影响颅内压[25]。(4)胸腔压力传递假说。该假说认为胸腹腔的冲击波通过大血管和软组织传入脑内,引起颅内压的升高[26]。(5)加速度假说。该假说认为加速度由头部的惯性运动引起,分为直线加速度和旋转加速度,可引起脑内的轴索损伤[27]。但是,多数研究者将其归为三级损伤的范畴。(6)脑脊液空化假说。该假说认为由于冲击波与头部的相互作用,在颅骨与脑脊液交界处出现局部瞬态负压,导致气泡形成,引起脑组织损伤[28]。冲击波的致伤机制可能是上述几种假说综合作用的结果,每种假说都有不同程度的证据支持,但目前尚没有确切的结论,还需更多的研究进行验证。
此外,致伤因素还具有累积效应,一定时间内多次暴露于损伤阈值以下的致伤因素,同样可以引起mTBI[22]。其原因可能是,当暴露于一次低水平损伤之后,脑内发生了可代偿的离子水平紊乱、兴奋性氨基酸水平升高、线粒体功能障碍等变化,但在几小时或数周内可逐步恢复而不出现相关症状;在这个时间窗内,如果个体再次遭受损伤,将会进一步加重上述病理生理改变,使其进展为失代偿状态而产生临床症状[29]。这种情况在战场环境较为常见,作战人员频繁暴露于爆炸环境中,部分mTBI伤员并没有明确的受伤经历,因而容易漏诊、误诊。
针对TBI损伤程度的判断,美国国防部制定了相关的判定标准,要点见表1[30]。按照该标准,被分类为轻型的TBI伤员即可被诊断为mTBI。mTBI无特异性临床表现,一般可分为躯体症状、认知改变和行为情感异常3类(表2);伤员多表现为其中一类症状。这3类症状并不相互排斥,还可相互作用或相互补充[31]
目前尚缺乏敏感度和特异度均较高的mTBI辅助诊断方法。头颅CT和常规MRI检查多用于排除中重型TBI。提高mTBI诊断的准确性,寻求有效的客观检查手段,一直是该领域研究的热点。目前相关研究主要集中在新的影像学检查指标和生物标志物两方面。
美国国防部对mTBI的诊断标准要求头部CT和常规MRI检查结果正常,如果报告异常结果,即应被归类为中型或重型TBI。近年来,由于计算机技术和物理科学的不断发展,研究者尝试将一些新的影像学检查指标用于mTBI的诊断。
一般认为mTBI的主要病理改变为创伤性轴索损伤,表现为轴索断裂或肿胀,因此,DTI应该能够显示该异常变化。但是,2011年Mac Donald等[32]的研究显示,伊拉克和阿富汗战争中大部分mTBI伤员的DTI结果并无异常,其诊断仍主要依靠临床表现。随着影像学技术的进步,新的纤维束成像算法可在大脑外围追踪小的纤维束,能够报告mTBI中细微的损伤。在mTBI中,急性期进行的DTI显示胼胝体、扣带束和海马伞的各向异性分数(fractional anisotropy,FA)减少且扩散性总体稍有增加,推测是由于损伤后的细胞毒性水肿引起的;在亚急性期,FA基本恢复正常,而扩散性总体下降,以平均扩散系数(mean diffusivity,MD)最为明显[33]。一项针对成人mTBI患者的荟萃分析显示,FA减少程度低与患者更好的认知功能预后相关,特别是记忆力和注意力方面。Yuh等[34]的临床研究显示,在发生mTBI后(11.2±3.3) d内进行DTI检查时,mTBI组较对照组FA显著减少,且减少程度与患者3个月和6个月的格拉斯哥预后评分(GCS)分值呈负相关。
SWI在显示脑内微出血方面的敏感度优于常规序列,具有较高的临床应用价值。Eldeş等[35]的研究显示,部分CT及MRI T2加权像和FLAIR序列显示正常的mTBI患者,SWI可在微出血灶显示出异常信号。
MRS可显示mTBI后的代谢改变。部分mTBI患者的颞叶可出现N-乙酰天冬氨酸(N-acetylaspartate,NAA)、NAA/肌酸(Cr)、NAA/胆碱复合物(Cho)值明显降低,Cho显著增高[36]。因为颞叶与记忆力密切相关,这反映了mTBI后记忆力下降的病理基础。
PET也是反映脑组织代谢障碍的一种检查手段。研究显示,mTBI伤员的小脑、蚓部、脑桥、内侧颞叶、扣带回后部等部位可出现葡萄糖代谢障碍[37]。PET-tau蛋白配体可用于慢性创伤性脑病的早期诊断和预后评估[38]。PET-苯二氮䓬受体复合物配体可用于评估神经炎症水平[39]
HRMRI可进行皮质厚度和皮质下结构体积测量。相关的动物实验显示,mTBI在急性期皮质水肿引起皮质厚度增加,随后发生华勒变性和反应性星形细胞增多,在慢性期皮质厚度降低[40]
fMRI可用于神经功能障碍的诊断、预后评估及治疗监测[41]。基于任务态和静息态的fMRI可为mTBI的诊断提供与功能障碍相关的客观信息,包括注意力、记忆力和情绪处理等方面[42]。它具有较高的临床实用价值,是当前研究的热点。任务态fMRI可以显示不同任务期间大脑激活的特定区域,当与记忆力、注意力和情绪处理相关的皮质区域及其联络纤维受损时,相关皮质激活受限。静息态fMRI可反映与躯体运动、视觉等相关的神经网络的完整性,对评估在战场上已失去肢体或者发生其他残疾伤员的神经功能具有明显的优势[43]
近年研究显示,部分生物标志物在TBI损伤严重程度判断及预后评估方面具有一定的临床价值,已成为TBI相关研究的重要领域。这些生物标志物涉及TBI后神经递质释放、自由基产生、钙介导损伤、基因激活、线粒体功能障碍、炎症反应和凝血功能异常等病理生理过程。部分生物标志物在TBI损伤早期就可出现在血清和脑脊液中,其敏感度和特异度往往比影像学检查更具优势;深入研究mTBI后生物标志物的变化及其规律,有助于弥补传统诊断方式的不足,为mTBI的诊断和治疗提供新的依据和线索。研究相对成熟的几种生物标志物及其临床意义见表3[44-51]。然而,在mTBI的诊断和预后评估方面,目前还没有单一的生物标志物兼具高特异度和高敏感度。当前较好的解决方案是联合应用多种生物标志物,或将生物标志物与影像学检查结合提高诊断的准确性。美军的相关指南中也不建议将生物标志物作为诊断和指导mTBI治疗的客观依据[52]
美军对mTBI的诊断主要是以“损伤事件”为前提,即伤员或目击者表明其经历了爆炸、交通事故或打架斗殴等,而后出现了上述临床表现,且符合表1中轻型TBI的分类标准,便可诊断为mTBI[53]。然而,由于mTBI缺乏有效的客观辅助诊断方法,其诊断主要依靠伤员的自我表达和目击者的描述,下列因素使其诊断的准确性下降:(1)伤后意识改变或丧失及逆行性遗忘是mTBI的主要特征,因此在没有目击者的情况下,很难确定受伤的情形;(2)认知障碍和情感异常也会降低患者陈述病史的可信度;(3)头痛、头晕、焦虑、抑郁等临床表现都是非特异性的,在人群中患病率本身就较高。
美军对mTBI的诊断目前常采用《军人急性脑震荡评估表》(military acute concussion evaluation,MACE)。MACE由美国国防和退伍军人脑损伤中心于2006年开发,以《脑震荡标准化评估表》(standardized assessment of concussion,SAC)为基础,制定后几经修改,内容不断增加,目前的最新版是2018年版[54]。MACE主要由位于或最接近受伤地点的一级救护所的卫生兵、军医或助理医师完成,强调在尽可能短的时间内对遭遇“损伤事件”的所有人员进行评估[55]。原版可在12~15 min完成评估,新版需要25~30 min。MACE分为病史和评估两部分:(1)病史部分,用于明确损伤事件的发生,且伤员的表现符合mTBI的标准。在病史部分,要求描述损伤事件、受伤原因、是否戴头盔、是否存在创伤后健忘症或意识丧失,以及是否存在脑损伤的相关症状(如头痛、头晕等)。(2)评估部分,包括认知评分、神经功能检查和症状三部分。它利用SAC中的项目来评估伤员的认知功能,包括定向力(5分)、注意力(5分)、瞬时记忆(15分)和长时记忆(5分),总分值30分。普通军人测试平均分值为28分,<25分则被认为有认知功能障碍。神经功能检查为简短的、定性的,用于评估瞳孔反应和眼动追踪、语言流畅性和单词查找以及步态或平衡障碍等。神经功能正常用 “绿色”表示,异常用“红色”表示。症状主要包括上述的头痛、头晕、记忆力下降、失眠、焦虑等,无症状用“A”表示,有一种或以上症状用“B”表示。例如,“23/红/B”表示认知功能评分值23分、神经功能检查异常和有症状,这便需要转至上级救治机构以接受进一步全面的诊治。
mTBI主要根据伤员的临床表现给予对症治疗,目前强调采用包括药物治疗和社会心理干预在内的综合方案[56]。由于对爆炸等因素的具体致伤机制仍不十分清楚,致伤因素暂不作为治疗方案的选择依据[52]。值得指出的是,mTBI不同症状之间具有复杂的联系,彼此之间互相影响(如头痛、失眠、认知障碍、情绪低落等),当一种症状经治疗得到缓解后,其他症状往往也能得到缓解。
2009年,美国国防部制定了mTBI的治疗指南,并在2016年根据新的研究进展进行了修订[52],针对相关症状的治疗制订了详细的方案,包括症状的背景介绍、评估方法及治疗建议。例如,头痛可见于约90%的mTBI伤员,且疼痛分级多处于中、重度,一般可分为三型:紧张性头痛、偏头痛和混合性头痛;评估需包括详细的病史询问、神经科查体和相关的治疗经过及疗效;治疗按不同时间段分别给予了用药建议(种类、剂量、不良反应及注意事项),同时强调社会关怀和心理疏导。
mTBI的救治标准应包括以下内容:(1)快速从战场上识别和后送可能发生mTBI的伤员,对其进行强制休息和神经功能评估;(2)早期规范的诊断和治疗方法;(3)对遗留的长期症状提供缓解和康复方案;(4)建立结构化的评估系统,判断伤员是否达到重返战场的标准。
近年来,美军对mTBI投入了大量的人力物力进行研究,以下列举几项他们的治疗经验:(1)在mTBI完全恢复之前,伤员是不能返回战场的,因为反复的mTBI将会延缓恢复进程,甚至造成永久损伤[57]。(2)伤员应在安静的环境中留观,如症状短期内不能缓解,则转至高级别的医疗中心,给予专科的医学和心理学治疗,并进行相关的影像学检查[13,53]。(3)完全卧床休息超过3 d可能并无益处,建议在身体情况允许和无暴露于发生TBI因素的风险时,尽早恢复日常活动[52]。(4)具有明确疗效的药物和非药物治疗手段有限,主要包括减少兴奋性氨基酸、非甾体抗炎药或激素抗炎、缓解头痛、抗焦虑、抗抑郁、肢体和心理康复治疗等[58-60]。(5)高压氧治疗可能有效[61]
我军近年来未经历过大规模的军事冲突,对于mTBI的救治经验除参考外军研究结果外,主要来自日常临床TBI病例或动物实验。在诊断方面,对各类血清标志物的变化趋势、敏感度和特异度、临床意义等都进行了深入研究,验证了其临床应用价值[62-64];影像检查方面,移动CT、移动MRI等设备逐步配备到医疗方舱和医院船等前线救治机构,为mTBI的早期诊断提供了有力支持[65-67]。在药物治疗方面,我军紧跟国际前沿,先后验证了S-亚硝基谷胱甘肽、去铁胺、壳寡糖、κ-阿片受体特异性激动剂等对mTBI的神经保护作用[68-71]。高压氧治疗也已应用于mTBI临床康复治疗中,并形成了专家共识[72]。更重要的是,为提升颅脑战创伤一线救治的时效性和救治质量,军内专家结合我军体制编制形式和联合作战特点编写了相应的培训教材,使一线官兵能掌握颅脑战创伤早期救治的要点,有利于降低相应的伤死率和伤残率。但是,由于缺乏相关病例的诊疗经验,尤其是缺乏长期随访的结果,对mTBI的治疗措施和救治流程还缺乏系统性和标准化,尚待进一步研究改进。
mTBI是现代战争中的“标志性损伤”,如不能得到早期诊治可能遗留多种后遗症,影响官兵后期的生活质量和战斗力恢复。mTBI防治的关键在于尽早发现并采取及时、有效、标准化的救治措施,缩短救治时间,以最大限度地改善伤员预后。然而,由于mTBI缺乏特异的临床表现和有效的辅助诊断方法,易发生漏诊、误诊。目前对mTBI的治疗主要是采取对症处理,强调药物治疗和社会心理干预的综合方案。建议我军进一步加大对mTBI的研究力度,改进相关救治指南和规范,以提高诊治水平,逐步建立标准化的救治体系。
  • 军队后勤科研计划项目(AHJ14J001)
  • 国家军用标准项目(BWS20B038)
  • 联勤保障部队装备综合研究项目(LB20191A010010)
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2023年第48卷第2期
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doi: 10.11855/j.issn.0577-7402.2023.02.0237
  • 接收时间:2022-04-22
  • 首发时间:2025-12-03
  • 出版时间:2023-02-28
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  • 收稿日期:2022-04-22
  • 录用日期:2022-06-22
基金
Scientific Research Projects of PLA Logistics(AHJ14J001)
军队后勤科研计划项目(AHJ14J001)
GJB Project(BWS20B038)
国家军用标准项目(BWS20B038)
Equipment Comprehesive Research Project of the Joint Service of PLA(LB20191A010010)
联勤保障部队装备综合研究项目(LB20191A010010)
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    解放军总医院第一医学中心神经外科医学部,北京 100853

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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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