Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia - Increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator - Results of a phase II clinical trial
Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia - Increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator - Results of a phase II clinical trial
复制标题
DOI：
10.1161/01.str.0000170707.86793.1a
复制
发表时间：
2005-07-01
期刊：
影响因子：
8.3
通讯作者：
Hennerici, MG
中科院分区：
文献类型：
--
作者：
Daffertshofer, M;Gass, A;Hennerici, MG
背景-在经颅多普勒设备中使用诊断频率的超声的临床研究提供了令人鼓舞的结果，在急性卒中中使用组织纤溶酶原激活剂（tPA）增强血栓溶解。低频超声不需要复杂的定位程序，穿透颅骨更好，并已被证明可以加速tPA在广泛的脑血管区域的动物实验中的溶栓，而没有出血的副作用。因此，我们进行了第一次多中心临床试验，以调查tPA加低频超声（300 kHz）的安全性。方法-包括6小时时间窗内的急性卒中患者（国立卫生研究院卒中量表评分> 4）。磁共振成像（MRI）用于记录血管闭塞并排除脑出血。将患者交替分配至联合治疗组;第1例患者仅接受tPA治疗，第2例患者接受tPA+超声治疗等。随访包括随后立即和24小时后的系列MRI，以确认再通和组织成像。结果- 26例患者（70.4 +/- 9.7岁）进入试验（12 tPA，14 tPA加超声）。研究提前停止，因为来自仅tPA组的12名患者中的5名，而用tPA加超声治疗的14名患者中的13名在MRI中显示出血迹象（P < 0.01）。治疗3天内，tPA+超声组发生5例症状性脑梗死。在3个月，无论是发病率，也没有治疗相关的死亡率或再通率两组之间的差异。结论-这项研究表明，从低频超声的生物效应，导致伴随治疗的患者与静脉tPA的脑出血率增加。
Background - Clinical studies using ultrasound at diagnostic frequencies in transcranial Doppler devices provided encouraging results in enhancing thrombolysis with tissue plasminogen activator (tPA) in acute stroke. Low-frequency ultrasound does not require complex positioning procedures, penetrates through the skull better, and has been demonstrated to accelerate thrombolysis with tPA in animal experiments in wide cerebrovascular territories without hemorrhagic side effects. We therefore conducted the first multicenter clinical trial to investigate safety of tPA plus low-frequency ultrasound (300 kHz).Methods - Acute stroke patients within a 6-hour time window were included (National Institutes of Health Stroke Scale scores > 4). Magnetic resonance imaging (MRI) was used to document vascular occlusion and to rule out cerebral hemorrhage. Patients were allocated to combination therapy alternately; the first patient received tPA only, the second patient received tPA plus ultrasound, etc. Follow-up included serial MRI directly thereafter and 24 hours later to confirm recanalization and tissue imaging. Clinical recovery was measured after treatment and 3 months later.Results - 26 patients (70.4 +/- 9.7 years) entered the trial (12 tPA, 14 tPA plus ultrasound). The study was prematurely stopped because 5 of 12 patients from the tPA only group but 13 of 14 patients treated with the tPA plus ultrasound showed signs of bleeding in MRI (P < 0.01). Within 3 days of treatment, 5 symptomatic hemorrhages occurred within the tPA plus ultrasound group. At 3 months, neither morbidity nor treatment- related mortality or recanalization rates differed between both groups.Conclusions - This study demonstrated bioeffects from low-frequency ultrasound that caused an increased rate of cerebral hemorrhages in patients concomitantly treated with intravenous tPA.