Ruth Thiex

Frame-based and frameless stereotactic hematoma puncture and subsequent fibrinolytic therapy for the treatment of spontaneous intracerebral hemorrhage

Comparison of two minimally invasive procedures for the treatment of intracerebral hemorrhage and subsequent lysis with regard to technical implications and clinical outcome of the patients. Retrospective analysis of 126 patients with spontaneous supratentorial intracerebral hemorrhage treated by frame-based (n=53) or frameless (n=75) hematoma aspiration and subsequent fibrinolysis with recombinant tissue plasminogen activator (rt-PA). Data were analysed for the whole group as well as for the two subsets of patients with regard to hematoma reduction, procedure-related complications, and the early and long term clinical outcome of the patients. Functional outcome was rated using the Glasgow Outcome Scale (GOS) and Barthel-Index (median follow-up 178 weeks). The prognostic impact of patient related covariates on the GOS was analysed using logistic regression analysis. 49 out of 126 patients (38.9 %) died, 25 of them in the early postoperative period. Only 22/126 (17.5 %) had a favorable long term outcome (GOS >3). Age > 65 years was significantly (p<0.03, OR 3.6) associated with a higher risk for an unfavorable long term outcome (GOS ≤ 3). Treatment had no impact on outcome. Both techniques were highly effective in reducing the intracerebral blood volume by 75.8±21.4% of the initial hematoma volume in frame-based and 64.8±25.4 % in frameless stereotaxy within 2 days of rt-PA-therapy. Malpositioning of the catheter occurred more often in the frameless group (21.3% vs. 9.4 % in the frame-based procedure) without gaining statistical significance. Frame-based and frameless stereotactic hematoma aspirations with subsequent fibrinolysis are effective in volume reduction of intracerebral hemorrhage with comparable clinical outcome. The frameless procedure is associated with a higher risk for malpositioning of the catheter. Despite effective hematoma reduction with both techniques, the percentage of patients with a good clinical outcome remained limited especially in the elder subpopulation.

TREATMENT OF EXPERIMENTALLY INDUCED ANEURYSMS WITH STENTS

OBJECTIVE: Although Guglielmi detachable coil systems have been widely accepted for treatment of intracranial aneurysms, primary stenting of aneurysms using porous stents, stent grafts, or implantation of coils after stent placement constitute emerging techniques in endovascular treatment. The aim of the present study was to use an animal model to investigate these different approaches to treat cerebral aneurysms with regard to the rate of closure and the histopathological changes within the aneurysm cavity and the parent vessel after stent placement. METHODS: We created aneurysms in 30 rabbits by distal ligation and intraluminal incubation of the right common carotid artery with elastase. Ten animals were treated with porous stents alone, 10 animals with stent grafts (covered stents), and 10 animals with stents and additional coiling via the interstices of the stent, which enabled dense packing of the coils. Five animals in each group were observed for 1 month and the other animals for 3 months. Histological analyses were performed, including immunohistochemical investigations for estimating the proliferation of the intima and possible inflammatory infiltration. RESULTS: Covered stents led to a complete and stable aneurysm occlusion with only minimal proliferative carrier vessel wall changes. One covered stent was completely occluded with old thrombus, and the other 9 remained patent. Porous stents occluded two of five aneurysms in the 1-month follow-up group and four of five after 3 months. However, progressive sprouting of neointima inside the carrier vessel that resulted in a stenosis of up to 40% was present. In the Stent + Coil group, one aneurysm showed recanalization after 1 month, and three of five aneurysms were recanalized after 3 months after coil compaction. Moreover, in-stent stenosis of up to 30% was present. CONCLUSION: This study demonstrates the possible shortcomings and problems of emerging stent techniques to treat intracerebral aneurysms, shows where technical advances have to be made, and describes in which cases of aneurysm morphology caution has to be exercised when considering an endovascular approach using stents.

The long-term effect of recombinant tissue-plasminogen-activator (rt-PA) on edema formation in a large-animal model of intracerebral hemorrhage

Abstract Hematoma puncture, fibrinolysis, and aspiration of the liquefied clot is a promising new treatment strategy for large intracerebral hemorrhages (ICH). Characteristics of the cellular injury and neuronal and glial cell death associated with ICH and the administration of fibrinolytic agents still need to be defined. We developed a porcine model to study the histopathological effects of recombinant tissue-Plasminogen-Activator (rt-PA) on perihematomatous cell integrity. In 20 pigs, lobar hematomas were induced by intracranial pressure (ICP)-controlled injections of 7.6 ± 1.6 ml of autologous blood into the white matter of the right frontal hemisphere. In nine animals, the clots were lysed with rt-PA, thereby facilitating aspiration 2 h after hematoma induction. In 11 control pigs, the hematoma resorption followed its natural course. The rate of hematoma reduction and edema formation over 10 days was evaluated on planimetry of the MRI data and correlated to the histopathological changes found at autopsy. Although rt-PA significantly accelerated clot resolution compared to controls ( p< 0.02), the increase of perihematomatous edema volume within 10 days was not significantly ameliorated in rt-PA-treated animals compared to controls on MRI. The extent of inflammatory infiltrates on histology was more pronounced in animals treated with rt-PA. In conclusion, despite significant reduction in the size of the hematoma clot liquefication with rt-PA and aspiration invokes a substantial inflammatory response when studied after 10 days and does not result in a reduction of the perihematomatous edema.

Time-of-flight-, phase contrast and contrast enhanced magnetic resonance angiography for pre-interventional determination of aneurysm size, configuration, and neck morphology in an aneurysm model in rabbits.

We describe three different magnetic resonance (MR)-angiography techniques to evaluate aneurysm size, configuration, and neck morphology of experimentally created aneurysms in a rabbit model. In five New Zealand White rabbits an aneurysm was created by endovascular occlusion of the right common carotid artery (CCA) using a pliable balloon and subsequent endoluminal incubation of elastase within the proximal CCA above the balloon and distal ligation of the vessel. In all animals, time-of-flight (TOF), phase contrast and contrast enhanced (CE) MR angiographies (MRA) were performed and compared to conventional digital subtraction angiography results. We found, that aneurysms are best visualized employing CE MRA, however, neck morphology was also found to demonstrate interpretable results when evaluating the axial source data of the TOF MRA. The animal model we used can be employed for testing endovascular devices such as new coil material, or covered stents. The described MRA techniques might then be helpful for pre-interventional planning and maybe even for the follow-up of the thus treated aneurysms.

Endovascular treatment of experimentally induced aneurysms in rabbits using stents: a feasibility study

Although Guglielmi detachable coil (GDC) systems have been generally accepted for treatment of intracranial aneurysms, primary stenting of aneurysms using porous stents or implantation of coils after stent placement remains experimental. Testing of these new methods requires an animal model which imitates human aneurysms in size, configuration and neck morphology. We assessed in detail the technical requirements of and steps for transfemoral stent treatment of experimentally induced aneurysms at the top of the brachiocephalic trunk in rabbits. We created aneurysms in ten rabbits by distal ligation and intraluminal digestion of the right common carotid artery with elastase. We treated five animals with porous stents alone, and five with stents plus coiling via the meshes of the stent, which permitted dense packing of coils. No complications related to the procedures occurred. In all animals, even in those treated solely with porous stents, total occlusion of the aneurysm was achieved. Our animal model can be suitable for testing the biocompatibility and occlusion rate of new methods and devices for the treatment of experimental aneurysms.

Haemorrhagic tracheal necrosis as a lethal complication of an aneurysm model in rabbits via endoluminal incubation with elastase

Background.We describe a lethal complication of an aneurysm model in rabbits for saccular aneurysmal creation via endoluminal incubation with elastase. Method. In 24 anaesthetized female New Zealand White rabbits, the right common carotid artery (CCA) was ligated distally to the arteriotomy. A 4F sheath was then placed retrograde into the CCA, and its origin was occluded endoluminally using a 2F Fogarty balloon. Elastase was incubated above the balloon in the separated vessel lumen for the duration of 20 minutes. Two weeks later, digital subtraction angiography was performed for aneurysm control. Two animals were then sacrificed and the aneurysm studied on histology. All animals that died within the experiment were examined post-mortem. Findings. Following this protocol, an aneurysm with a mean size of 7.6×3.2 mm could be created in 11 out of 24 animals. 9 out of 13 animals with lethal outcome died from haemorrhagic necrosis of the trachea with subsequent pulmonary complications. DSA releaved an arterial branch originating from the proximal CCA in a near 90 °-angle aiming at the trachea. Interpretation. The endoluminal incubation with elastase is suitable for aneurysm creation of reproducible size that are suited to test new endovascular devices such as stents and new coils. One should always be aware of an arterial branch of the CCA supplying the trachea. In case of elastase instillation into this branch, lethal haemorrhagic necrosis of the trachea occurs. Bearing this complication in mind, we have experienced a minimal loss of animals in subsequent studies.

Hyperacute Perimesencephalic subarachnoid hemorrhage : Demonstration of blood extravasation with MRI

Perimesencephalic subarachnoid hemorrhage (SAH) is a benign subtype of SAH without known vascular pathology. We report a case of current subarachnoid bleeding in the vicinity of the basilar artery. The patient was on anticoagulation medication and had sustained a head injury 2 days earlier. The bleeding was documented by contrast agent extravasation in MRI. Because of the isointensity of hyperacute blood to CSF in conventional T2 sequences, FLAIR images are mandatory for diagnosis in the hyperacute state.

The role of intraoperative magnetic resonance imaging for the detection of hemorrhagic complications during surgery for intracerebral lesions an experimental approach.

BACKGROUND Intraoperative magnetic resonance imaging (MRI) for guided biopsy or microsurgical resection of intracranial lesions is gaining broader acceptance. It is not known whether intraoperative MRI has the potential to detect hemorrhagic complications of these surgical procedures, because scientific research has so far focussed on the signal characteristics of less acute clots. It is the objective of this experimental study to investigate whether MRI can visualise intracerebral blood within minutes after its occurrence. METHODS In 26 pigs, a frontal hematoma was produced by injecting autologous blood. Twenty pigs underwent MRI 30 minutes after injection, and 6 pigs within the first 10 minutes. MRI scans were performed on a 1.5T system. T1-weighted spin echo (SE), T2-weighted turbo spin echo (TSE), T2-weighted fluid attenuated inversion recovery (FLAIR), and T2-weighted gradient echo (GE) images were acquired. Depending on the differences of the signal intensities of the hematoma and the surrounding brain, the detectability of the hematoma was rated as good, fair, or poor. RESULTS None of the induced hematomas were rated to be clearly visible on T1-weighted sequences. Six of the 26 hematomas (23%) were easily detectable on FLAIR sequences, 18 hematomas (69%) on T2-weighted TSE sequences, and 23 hematomas (88%) on the T2-weighted GE sequences. CONCLUSION Extravasated blood can be identified with a high reliability within minutes after its occurrence on MRI provided that T2-weighted GE sequences are used for imaging. In conclusion, intraoperative MRI is not only of value for guidance of neurosurgical procedures, but also for immediate detection of hemorrhagic complications.

Minor inflammation after surgical evacuation compared with fibrinolytic therapy of experimental intracerebral hemorrhages

Abstract Objectives: Toxic components released from the intracerebral blood clot, such as thrombin and hemoglobin, potentially trigger brain edema formation and therefore favor an early evacuation of the clot. Despite a significant reduction in hematoma size in our porcine model of hematoma induction by injecting autologous blood ICP-controlled into the right frontal white matter with subsequent fibrinolysis using recombinant tissue-plasminogen activator (rt-PA) and aspiration of the liquefied clot (n=9), local rt-PA promoted delayed perihematomatous edema formation and invoked a substantial inflammatory reaction compared with controls (n=11). Methods: We therefore modified our formerly developed porcine model of intracerebral hemorrhage in removing the hematoma by open craniotomy and suction of the clot in seven animals. The residual hematoma size and extent of perifocal edema were evaluated over 10 days on planimetry of the MRI data, and correlated to the histopathological changes of edema and inflammation found at autopsy. Results: The edema volume on day 4 was significantly less in the surgical group compared with the lysis group (p<0.03). On day 10, however, the difference in edema size was not statistically significant compared with the lysis group (p<0.07) and the control group (p<0.09). The inflammatory response was minor compared with the lysis and control group. Discussion: In conclusion, despite a significant reduction in hematoma size by surgical removal of the clot, only the inflammatory response, but not the extent of delayed edema can be positively influenced.

Treatment of Experimental Aneurysms in Rabbits Using Guglielmi Detachable Coils: A Feasibility Study

The Guglielmi detachable coil (GDC) has been generally accepted in the treatment of intracranial aneurysms. Preclinical testing of new coil developments requires animal models of aneurysms that imitate human aneurysms in size, configuration and neck morphology. priate approach and the adequate endovascular devices that are necessary for a safe treatment of the experimentally induced pathology. The goal of the present work was to elaborate the procedural and technical requirements which are needed for a safe and practicable endovascular therapy of these experimentally induced aneurysms. Treatment of Experimental Aneurysms in Rabbits using Guglielmi Detachable Coils A Feasibility Study