Abstract
Catheter-based ultrasound-thrombolysis has been successfully used in a small clinical trial in order to enhance recombinant tissue plasminogen activator (rtPA)-fibrinolysis, for the treatment of spontaneous intracerebral hemorrhages (ICHs). The aim of this study was to investigate the ultra-early effects of ultrasound on hematoma and the surrounding brain tissue in a porcine ICH-model. To achieve this, 21 pigs with a right frontal ICH were randomly assigned to four groups: (1) drainage (n = 3), (2) drainage + rtPA (n = 6), (3) drainage + ultrasound (n = 6), and (4) drainage + ultrasound + rtPA (n = 6). The hematoma volume assessment was performed using cranial MRI before and after the treatments. Subsequently, the brain sections were analyzed using HE-staining and immunohistochemistry. The combined treatment using rtPA and ultrasound led to a significantly higher hematoma reduction (62 ± 5%) compared to the other groups (Group 1: 2 ± 1%; Group 2: 30 ± 12%; Group 3: 18 ± 8% (p < 0.0001)). In all groups, the MRI revealed an increase in diffusion restriction but neither hyper- or hypoperfusion, nor perihematomal edema. HE stains showed perihematomal microhemorrhages were equally distributed in each group, while edema was more pronounced within the control group. Immunohistochemistry did not reveal any ultra-early side effects. The combined therapy of drainage, rtPA and ultrasound is a safe and effective technique for hematoma-reduction and protection of the perihematomal tissue in regard to ultra-early effects.
Highlights
The treatment of spontaneous, intracerebral hemorrhage (ICH) is still subject to debate, and guidelines concerning evidence-based, first-line therapy and the role of surgical treatment are needed in the future [1]
FORo3P.fE0E15R.5±R1E0±V.2IE10W.c5mc3m(3p, which was significantly lower than the volume of the control group = 0.002) the volume of the group treated with recombinant tissue plasminogen activator (rtPA) 2.41 ± 0.61 cm3 (p = 0.0278) and the volume of Group 3 2.75 ± 0.44 cm3 (p = 0.0023) (Figure 2a)
The transcranial use of ultrasound was the subject of many phase three clinical trials in the last twenty years [12,13,15,17,18,19,20,21,22,31,32], only one clinical study investigated the possibility of increasing rtPA fibrinolysis of ICH using intrahematomal ultrasound [11]
Summary
The treatment of spontaneous, intracerebral hemorrhage (ICH) is still subject to debate, and guidelines concerning evidence-based, first-line therapy and the role of surgical treatment are needed in the future [1]. There are believed to be 5 million incidences of ICH per year worldwide [2]. This fatal subtype of stroke has the highest rate of death, and a one-year mortality of approximately 50%. Craniotomy studies have failed to show any improvement in survival and functional outcome in ICH patients [4,5] (with the exception of superficial lobar ICHs) [6]. In a meta-analysis of 15 high-quality randomized controlled trials (with a 3–12 month follow up), minimally invasive surgery (MIS) for ICH (including endoscopic surgery and stereotactic thrombolysis by rtPA), increased the chance of being independent by 2.2 times and the survival by 1.7 times, when compared to conventional craniotomy and conservative treatment (performed within 24–72 h) [7]. It is difficult to draw conclusions about any subgroup superiority in these wide-scattered studies, as the heterogeneity of influencing factors like age, follow-up time, hematoma volume and location, study size, scope of collected data, time until treatment, inflammation, oxidative stress, toxicity of blood degradation products and scope of monitoring, all have to be considered
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