TIA

1 前言：TIA是综合症，复发率和预后差于卒中，超出大家的想象 短暂性脑缺血发作的中国专家共识（草稿） 一、前言： 传统观点认为短暂性脑缺血发作（TIA）是“良性、可逆性脑缺血综合征”，复发风险低于脑梗死。然而，研究 表 关于同志近三年现实表现材料材料类招标技术评分表图表与交易pdf视力表打印pdf用图表说话 pdf 明[1]，TIA患者7d内出现卒中的风险为8%左右，30d达10%，而90d内出现卒中的风险则为10%-20%（平均为11%），而急性卒中90d内卒中复发的风险近为2%-7%（平均为4%），显著低于TIA患者。此外，TIA患者不仅会发生脑梗死，而且出现心肌梗死和猝死的风险也很高。90d内TIA复发、心肌梗死和死亡事件总的风险高达25%。因此，TIA是严重的、需紧急干预的“卒中预警”事件，亟待更新观念，加强重视。而目前我国TIA的诊治领域“低估、误判”现象严重；“救治不及时、不规范”等问题突出，鉴于此，中华内科杂志编辑部特约请国内神经病学专家充分讨论并最终达成TIA概念、发病机制、病因分层评估与治疗决策的专家共识。 二、概念： （一）历史回顾 传统“基于时间”的TIA概念起源于上世纪50-60年代，1958年Fisher[2]认为TIA可以持续几h，一般为5-10min；1964年，Acheson和Hutchinson[3]支持使用1h的时间界限；1964年，Marshell[4]建议使用24h概念；1965年，美国第四届普林斯顿会议[5]将TIA定义为“突然出现的局灶性或全脑神经功能障碍，持续时间不超过24h，且排除非血管源性原因”。美国国立卫生研究院（NIH）脑血管病分类于1975年采用了此定义[6]，并一直沿用至今。 然而，随着现代影像学的进展，基于“时间和临床”的传统定义受到了诸多质疑。研究表明，大部分TIA患者的症状持续时间不超过1h，超过1h的患者在24h内可以恢复的几率很小。而且部分临床症状完全恢复的患者影像学已提示存在梗死。鉴于此，TIA工作组在2002年提出了新的TIA概念[7]：“由于局部脑或视网膜缺血引起的短暂性神经功能缺损发作，典型临床症状持续不超过1h, 且在影像学上无急性脑梗死的证据”。TIA新概念把TIA的时间界限缩短为1 h，这意味着如果症状持续1h以上，应按照急性卒中 流程 快递问题件怎么处理流程河南自建厂房流程下载关于规范招聘需求审批流程制作流程表下载邮件下载流程设计 进行处理；同时新概念也将TIA与卒中的界定由传统的“时间和临床症状”标准改进为“组织学损害”标准（表1）。 但这一概念至今尚未被各国的疾病分类所采纳。 表1、 新旧TIA概念的比较 基于时间的传统概念 基于组织的新概念 基于传统24h时间界限 基于是否存在生物学终点 一过性缺血性症状是良性的 提示一过性缺血性症状可以引起持续脑损害 诊断基于一过性过程而并非病理生理 鼓励使用辅助检查确定有无脑损害及其原因 导致急性脑缺血治疗的延误 促进快速急性脑缺血的治疗 不准确提示有无缺血性脑损害 更准确反映缺血脑损害 与心绞痛和心肌梗死的概念相悖 与心绞痛和心肌梗死的概念一致 （二）建议 TIA和脑梗死之间并没有截然的区别，二者应被视为一个缺血性脑损伤动态演变过程的不同阶段。建议在有条件的医院，尽可能采用新概念——即“组织学损害”的标准界定二者，对症状持续1h以上者，应按照急性卒中流程紧急救治。 三、发病机制： （一）文献复习 一般认为[8]，TIA主要病因与发病机制常分为血流动力学型和微栓塞型。 血流动力学型TIA是在动脉严重狭窄基础上血压波动导致的远端一过性脑供血不足引起的，血压低于脑灌注失代偿的阈值时发生TIA，血压升高脑灌注恢复时症状缓解，这种类型的TIA占很大一部分。 微栓塞型又分为心源性栓塞和动脉-动脉源性栓塞。动脉-动脉源性栓塞是由大动脉源性粥样硬化斑块破裂所致，斑块破裂后脱落的栓子会随血流移动，栓塞远端小动脉，如果栓塞后栓子很快发生自溶，即会出现TIA。在这种情况下，抗血小板聚集和稳定斑块的治疗是最重要的。心源性栓塞型TIA的发病机制与心源性脑梗死相同，其发病基础主要是心脏来源的栓子进入脑动脉系统引起血管阻塞，如栓子自溶则形成心源性TIA。 血流动力学型与微栓塞型TIA的临床鉴别要点见表2[9] 。 表2 血流动力学型与微栓塞型TIA的临床鉴别要点 临床表现 血流动力学型 微栓塞型 发作频率 密集 稀疏 持续时间 短暂 较长 临床特点 刻板 多变 （二）建议 TIA是一个综合征。不同病因决定不同的临床决策，预后也不尽相同，因此更应重视TIA的病因与发病机制诊断。建议TIA的主要发病机制可以分为血流动力学型，动脉-动脉栓塞型和心源性栓塞型。（还应包括原位微小血栓形成型！） 四、临床评价与治疗决策 （一）临床评价建议 1、积极评价危险分层、高危患者尽早收入院 预后研究的结果[1]提示，TIA患者在发病后前3个月内发生脑梗死的风险较大，其中前2d风险最大，患者的处理应越早越好。因此，对于初发TIA患者、进展型TIA患者、症状持续时间>1h、症状性颈内动脉狭窄>50％、已知的心脏来源的栓子（如心房颤动）、己知的高凝状态、加利福尼亚评分或ABCD评分（见附录）的高危患者，在发病24～48h内应考虑收入院进一步评价、治疗（见图1）[1, 10-12]。 2、新发TIA应按“急症”处理 新近发生（48h内）的TIA预示短期内具有发生卒中的高度危险，应作为重要的急症处理，新发TIA患者处理流程见图1[13]。 图1、可疑TIA处理流程 3、尽早完善各项相关检查 首先，对于怀疑TIA患者应尽可能行DWI检查，明确是否为TIA。TIA发作但未被收入院的患者应该通过快速急救通道（12h内）进行紧急评估和检查（如头颅CT或MRI、心电图、颈动脉多普勒超声）。如果头颅CT、心电图或颈动脉多普勒超声未在急诊完成，那么初始的评估应在24－48h内完成。如果在急诊完成，且结果阴性，那么可将初始评估的时间适当延长（如：直到7 d）[10]，以明确缺血发生的机制及随后的预防治疗。 4、全面的检查及评估 1）一般检查：评估包括心电图、全血细胞计数、血电解质、肾功能及快速血糖和血脂测定[10]。 2）血管检查：应用CT、CTA、MRI、MRA可发现梗死和重要的颅内外血管疾病。颈动脉影像脑血管造影（DSA）是颈动脉内膜剥脱术（CEA）和颈动脉支架治疗（CAS）的金标准检查，在确认颈部多普勒超声检查的准确性以后，才被推荐用于颈动脉狭窄的术前评估[10, 14]。 3）侧支循环代偿及脑血流储备评估：应用DSA、脑灌注成像和/或经颅彩色多普勒超声（TCD）检查评估侧支循环代偿及脑血流储备，对于鉴别血流动力学型TIA及指导下一步治疗非常必要[10]。 4）不稳定斑块的检查：不稳定斑块是动脉栓子的重要来源。颈部血管超声、血管内超声、MRI及TCD微栓子监测有助于动脉粥样硬化的不稳定斑块进行评价[10]。 5）心脏评估：TIA后，当怀疑心源性栓塞机制时，对45岁以下的患者，如果颈部和脑血管检查及血液学筛选未能对TIA的病因提供有效线索，则推荐对其进行经胸壁超声心动图（TTE）和/或经食管超声心动图（TEE）检查，可能发现心脏附壁血栓、房间隔的异常（房室壁瘤、卵圆孔未闭、房间隔缺损）、二尖瓣赘生物以及主动脉弓粥样硬化等多种心源性栓子的来源[10, 15]。 6）根据病史做其他进一步检查[13]见表3： 表3 特殊病史可疑TIA患者的评价 病史 提示 检查 产后或脱水状态下头痛 静脉血栓 MRI、MRV和DSA 青年女性，有自发流产史，静脉血栓史，血小板减少，陈旧多发梗塞灶 抗心磷脂抗体综合征 抗心磷脂抗体 发热 亚急性或急性细菌性心内膜炎 血培养，强化或不强化CT。在确定细菌性心内膜炎的部分病人，实施脑血管造影以除外细菌性动脉瘤 意识浑浊、头痛、癫痫 CNS血管炎 脑血管造影、血沉、腰椎穿刺 　 高血压脑病 血压监测、考虑MRI 风湿病，使用拟交感药物 CNS血管炎 脑血管造影、血沉、腰椎穿刺（是否有白细胞升高） 新近心肌梗死 心源性栓塞 经胸或经食道超声心动图 头颈或下颌疼痛，尤其是创伤后 颈动脉或椎动脉夹层 考虑脑血管造影或其他颈部血管影像学检查 突然严重头痛，伴畏光或晕厥 蛛网膜下腔出血 急诊CT，如果CT阴性做腰穿。脑血管造影除外动脉瘤或动静脉畸形 意识模糊，模糊，昏迷，其他脑干症状 椎基底动脉缺血 考虑MRA或DSA，如基底动脉有血栓，考虑动脉溶栓 　 脑水肿，脑疝 即刻头部CT，如果CT阳性，急诊手术 无明显卒中危险因素 隐匿性卒中，卵圆孔未闭，房间隔瘤，瓣膜或主动脉弓病变 考虑脑血管造影，经食道超声心动图，高凝状态相关检查 （二）治疗决策建议 建议针对不同的病因进行分层，采用不同的治疗决策（图2）。 1、内科治疗 1）心源性栓塞性TIA 持续性或阵发性（瓣膜性或非瓣膜性的）心房颤动的TIA患者，建议长期口服华法令抗凝治疗（感染性心内膜炎患者除外），其目标INR值为2.5 (范围为2.0 – 3.0)。对于抗凝药物禁忌症的患者，推荐其使用阿司匹林(75-150 mg/d)，如果阿司匹林不能耐受者，应用氯吡格雷(75 mg/d)。窦性节律的TIA患者不应使用抗凝药物，除非具有心源性栓塞的高度风险（突发的心房颤动或心房扑动、近期的心肌梗死、机械的心脏瓣膜修复术、二尖瓣狭窄、心内血块、或严重的扩张性心肌病[EF<20%]）[10, 16-20]。具体推荐参见2006美国心脏病协会缺血性卒中和TIA二级预防指南[21]。 2）非心源性栓塞性TIA 不推荐使用口服抗凝药物[22]。应建议其进行长期的抗血小板治疗。常用的药物为阿司匹林[21]（75-150mg/d），而有资料表明氯吡格雷（75mg）[23-25]可能较阿司匹林更有效。 3）动脉-动脉栓塞性TIA 治疗包括抗血小板聚集、稳定斑块及强化降脂治疗。建议对于无禁忌症的患者，联合使用阿司匹林（75-150mg）和氯吡格雷（75mg）[26, 27]、他汀类药物（低密度脂蛋白目标值在80 mg/dl或2.1 mmol/L以下）[21, 28]及丙丁酚（0.5g bid）[29]。 4）血流动力学性TIA 除抗血小板聚集、降脂治疗外，血压管理需要慎重，应停用降压药物，必要时给以扩容治疗，有条件的医院，可以考虑血管内或外科治疗[21, 29]。在大动脉狭窄已经解除的情况下，可以考虑将血压控制到目标值以下。 5）其他 血流动力型TIA患者禁用尼莫地平等抗血管痉挛药物[29]。 传统观念认为TIA和小卒中因预后好而不能从超早期tPA溶栓中获益，然而，有研究表明[30]，尽管症状迅速恢复，但此亚组人群的预后并不良，且tPA溶栓后症状性出血的风险较小（2%），溶栓总体获益并不低于中重度卒中。因此，对于TIA（包括小卒中）患者不应轻易的将其作为tPA溶栓的排除人群，需要进一步研究[31]。 应加强对TIA各种危险因素的控制，具体推荐参见2006美国心脏病协会缺血性卒中和TIA二级预防指南[21]。 2、外科手术及血管内治疗 1）颅外颈动脉粥样硬化性狭窄 新发（6个月内）、同侧颈动脉重度狭窄（NASCET (North American Symptomatic Carotid Endarterectomy Trial) 测量标准70%-99%）的TIA患者，在有条件的医院（围手术期卒中和死亡事件发生率<6%），（2005年的美国神经病学会指南推荐[32]患者应符合40～75岁,预期寿命至少有5年），建议行CEA或CAS。新发缺血性卒中或TIA、同侧颈动脉中度狭窄（50%-69%）的患者建议根据其具体情况（年龄、性别、合并疾病及发作时症状的严重程度或最佳内科治疗无效者）行CEA或CAS。狭窄程度<50%时不适合行CEA[32-37]。 TIA患者有CEA或CAS适应症时，建议治疗在2周内进行[21]。 对于症状性颈动脉闭塞患者，不常规推荐颅内外搭桥手术[21]。 2）椎基底动脉/颅内动脉粥样硬化性狭窄 对于经内科治疗（抗栓药物、他汀类药物及其它控制危险因素的治疗）仍有症状发作的血流动力学性严重（狭窄率>70%）颅内动脉粥样硬化狭窄或椎基底动脉狭窄的TIA患者，有条件的医院可考虑CAS [38-45]。 附录 加利福尼亚评分 ​ 年龄>60 岁 (1) ​ 糖尿病 (1) ​ 症状持续时间>10 min (1) ​ 肢体无力 (1) ​ 言语功能障碍 (1) 最终评分0-5 Johnston et al. JAMA 2000; 284:2901 ABCD评分 ​ 年龄>60 岁 (1) ​ 血压（mm Hg）：SBP >140 或 DBP>90 (1) ​ 临床症状： a)​ 单侧无力 (2) b)​ 不伴无力的言语障碍 (1) ​ 症状持续时间 c)​ >60 min (2) d)​ 10-59 min (1) 最终评分 0-6 Rothwell et al. Lancet 2005;366:29 参考文献 1 Johnston SC, Gress DR, Browner WS, et al. Short-term prognosis after emergency department diagnosis of TIA. JAMA, 2000,284:2901-6.2 Fisher CM, ed. Intermittent cerebral ischemia. New York:New York: Grune & Stratton,1958. 81-97.3 ACHESON J, HUTCHINSON EC. OBSERVATIONS ON THE NATURAL HISTORY OF TRANSIENT CEREBRAL ISCHAEMIA. Lancet, 1964,22:871-4.4 MARSHALL J. THE NATURAL HISTORY OF TRANSIENT ISCHAEMIC CEREBRO-VASCULAR ATTACKS. Q J Med, 1964,33:309-24.5 Siekert RG, Whisnant JP, eds. Cerebral vascular diseases: fourth conference:New York: Grune & Stratton,1965.6 A classification and outline of cerebrovascular diseases. II. Stroke, 1975,6:564-616.7 Albers GW, Caplan LR, Easton JD, et al. Transient ischemic attack--proposal for a new definition. 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Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke, 2006,37:577-617.22 Chimowitz MI, Lynn MJ, Howlett-Smith H, et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med, 2005,352:1305-16.23 Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet, 2004,364:331-7.24 A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. 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Outcome, observer reliability, and patient preferences if CTA, MRA, or Doppler ultrasound were used, individually or together, instead of digital subtraction angiography before carotid endarterectomy. J Neurol Neurosurg Psychiatry, 2002,73:21-8. 15 Kapral MK, Silver FL. Preventive health care, 1999 update: 2. Echocardiography for the detection of a cardiac source of embolus in patients with stroke. Canadian Task Force on Preventive Health Care. CMAJ, 1999,161:989-96. 16 Hart RG, Pearce LA, Koudstaal PJ. Transient ischemic attacks in patients with atrial fibrillation: implications for secondary prevention: the European Atrial Fibrillation Trial and Stroke Prevention in Atrial Fibrillation III trial. Stroke, 2004,35:948-51. 17 Yamaguchi T. Optimal intensity of warfarin therapy for secondary prevention of stroke in patients with nonvalvular atrial fibrillation : a multicenter, prospective, randomized trial. 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Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke, 2006,37:577-617. 22 Chimowitz MI, Lynn MJ, Howlett-Smith H, et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med, 2005,352:1305-16. 23 Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet, 2004,364:331-7. 24 A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet, 1996,348:1329-39. 25 Ringleb PA, Bhatt DL, Hirsch AT, et al. Benefit of clopidogrel over aspirin is amplified in patients with a history of ischemic events. Stroke, 2004,35:528-32. 26 Peters RJ, Mehta SR, Fox KA, et al. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Circulation, 2003,108:1682-7. 27 Dittrich R, Ritter MA, Kaps M, et al. The use of embolic signal detection in multicenter trials to evaluate antiplatelet efficacy: signal analysis and quality control mechanisms in the CARESS (Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic carotid Stenosis) trial. Stroke, 2006,37:1065-9. 28 Amarenco P, Bogousslavsky J, Callahan A 3rd, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med, 2006,355:549-59. 29 In: 北京神经病学学术沙龙, ed. BNC脑血管病临床指南. 北京:人民卫生出版社,2002. 36-40；138-142. 30 Smith EE, Abdullah AR, Petkovska I, et al. Poor outcomes in patients who do not receive intravenous tissue plasminogen activator because of mild or improving ischemic stroke. Stroke, 2005,36:2497-9. 31 Lyden P, Lu M, Kwiatkowski T, et al. Thrombolysis in patients with transient neurologic deficits. Neurology, 2001,57:2125-8. 32 Bates ER, Babb JD, Casey DE Jr, et al. ACCF/SCAI/SVMB/SIR/ASITN 2007 clinical expert consensus document on carotid stenting: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents (ACCF/SCAI/SVMB/SIR/ASITN Clinical Expert Consensus Document Committee on Carotid Stenting). J Am Coll Cardiol, 2007,49:126-70. 33 Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med, 1991,325:445-53. 34 MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. European