Alexandrov Andrei V, Hall Christiana E, Labiche Lise A, Wojner Anne W, Grotta James C
Center for Noninvasive Brain Perfusion Studies, Stroke Treatment Team, University of Texas-Houston Medical School, 77030, USA.
Stroke. 2004 Feb;35(2):449-52. doi: 10.1161/01.STR.0000113737.58014.B4. Epub 2004 Jan 15.
Early arterial recanalization (ER) with intravenous tissue plasminogen activator (tPA) can lead to dramatic clinical recovery, whereas some patients do not experience immediate clinical improvement.
Consecutive patients received tPA 0.9 mg/kg IV within 3 hours after symptom onset. All had M1 or M2 middle cerebral artery occlusions on pretreatment transcranial Doppler. Patients were continuously monitored for 2 hours after bolus. ER was defined as the Thrombolysis in Brain Ischemia intracranial flow increase by >or=1 grade. Stroke severity (National Institutes of Health Stroke Scale [NIHSS]) and recovery (modified Rankin Scale) were assessed independently of transcranial Doppler.
One hundred twenty patients (mean age, 68+/-15 years; 63 women; median NIHSS, 17; range, 5 to 29; 90% with >or=10 points) received tPA at a median of 120 minutes, 50% within the first 2 hours. ER was observed in 73 patients (32 complete, 41 partial). No immediate clinical changes (n=23) or worsening (by 1 to 6 points on NIHSS, n=4) was observed in 37% of ERs (nonresponders). Complete ER was found in 8 of these 27 patients. At 24 hours, 22 of 27 patients (82%) had persisting deficits of NIHSS >or=10 points, yet 37% of these nonresponders (10 of 27) still achieved good outcome (modified Rankin score, 0 to 2) at 3 months. Among nonresponders with good outcome, 100% had detectable residual flow signals, and 70% had compensatory flow diversion on prebolus transcranial Doppler compared with 65% and 29% of nonresponders with poor outcome (P<0.05). Compared with responders (n=46), nonresponders had similar prebolus median NIHSS of 16 to 17 points, bolus times of 120 to 132 minutes, median speed of thrombolysis (30 minutes), and ER times of 190 to 193 minutes after onset. Reocclusion occurred in 3 of 4 patients with clinical worsening, 30% of other nonresponders, and 22% of responders. Symptomatic hemorrhage rate was 4% in both groups. At 3 months, mortality was 33% in nonresponders compared with 9% in responders (P=0.001).
After successful arterial ER with tPA therapy, lack of early clinical changes or worsening is relatively common (37%) and appears to be independent of time to tPA bolus or reperfusion. However, with tPA alone, at least one third of these nonresponders still achieved good outcomes at 3 months, suggesting the possibility of a "stunned brain" syndrome with delayed recovery. Several different mechanisms may potentially account for this phenomenon.
静脉注射组织型纤溶酶原激活剂（tPA）实现早期动脉再通（ER）可使临床症状显著改善，然而部分患者并未立即出现临床症状改善。
连续纳入症状发作后3小时内静脉注射0.9mg/kg tPA的患者。所有患者治疗前经颅多普勒检查均显示大脑中动脉M1或M2段闭塞。推注药物后对患者连续监测2小时。ER定义为脑缺血溶栓治疗颅内血流增加≥1级。独立于经颅多普勒检查评估卒中严重程度（美国国立卫生研究院卒中量表[NIHSS]）及恢复情况（改良Rankin量表）。
120例患者（平均年龄68±15岁；63例女性；NIHSS中位数为17；范围5至29；90%患者NIHSS≥10分）在症状发作后中位数120分钟接受tPA治疗，50%患者在最初2小时内接受治疗。73例患者（32例完全再通，41例部分再通）出现ER。37%的ER患者（无反应者）未出现即刻临床变化（n = 23）或病情恶化（NIHSS增加1至6分，n = 4）。这27例患者中有8例实现完全ER。24小时时，27例患者中有22例（82%）NIHSS持续≥10分，但这些无反应者中37%（27例中的10例）在3个月时仍获得良好预后（改良Rankin评分0至2分）。在预后良好的无反应者中，100%患者可检测到残余血流信号，推注前经颅多普勒检查显示70%患者存在代偿性血流分流，而预后不良的无反应者分别为65%和29%（P<0.05）。与有反应者（n = 46）相比，无反应者推注前NIHSS中位数为16至17分，推注时间为120至132分钟，溶栓中位数速度（30分钟），症状发作后ER时间为190至193分钟。4例临床症状恶化患者中有3例出现再闭塞，其他无反应者中30%出现再闭塞，有反应者中22%出现再闭塞。两组症状性出血率均为4%。3个月时，无反应者死亡率为33%，有反应者为9%（P = 0.001）。
tPA治疗成功实现动脉ER后，缺乏早期临床变化或病情恶化相对常见（37%），且似乎与tPA推注时间或再灌注时间无关。然而，仅使用tPA时，这些无反应者中至少三分之一在3个月时仍获得良好预后，提示可能存在“脑休克”综合征及延迟恢复。几种不同机制可能解释这一现象。
