Head or Neck First? Speed and Rates of Reperfusion in Thrombectomy for Tandem Large Vessel Occlusion Strokes.

BACKGROUND: We aim to evaluate the speed and rates of reperfusion in tandem large vessel occlusion acute stroke patients undergoing upfront cervical lesion treatment (Neck-First: angioplasty and/or stent before thrombectomy) as compared to direct intracranial occlusion therapy (Head-First) in a large international multicenter cohort. METHODS: The Thrombectomy In TANdem Lesions (TITAN) collaboration pooled individual data of prospectively collected thrombectomy international databases for all consecutive anterior circulation tandem patients who underwent emergent thrombectomy. The co-primary outcome measures were rates of successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/3) and time from groin puncture to successful reperfusion. RESULTS: In total, 289 patients with tandem atherosclerotic etiology were included in the analysis (182 Neck-First and 107 Head-First patients). Except for differences in the Alberta Stroke Program Early CT Score (ASPECTS; median 8 [range 7-10] Neck-First vs. 7 [range 6-8] Head-First; p < 0.001) and cervical internal carotid artery (ICA) lesion severity (complete occlusion in 35% of the Neck-First vs. 57% of the Head-First patients; p < 0.001), patient characteristics were well balanced. After adjustments, there was no difference in successful reperfusion rates between the study groups (odds ratio associated with Neck-First: 1.18 [95% confidence interval, 0.60-2.17]). The time to successful reperfusion from groin puncture was significantly shorter in the Head-First group after adjustments (median 56 min [range 39-90] vs. 70 [range 50-102]; p = 0.001). No significant differences in the rates of full reperfusion, symptomatic hemorrhage, 90-day independence, or mortality were observed. Sensitivity analysis excluding patients with complete cervical ICA occlusion yielded similar results. CONCLUSIONS: The upfront approach of the intracranial lesion in patients with tandem large vessel occlusion strokes leads to similar reperfusion rates but faster reperfusion as compared to initial cervical revascularization followed by mechanical thrombectomy. Controlled studies are warranted.

Hemorrhagic Transformation After Thrombectomy for Tandem Occlusions.

Background and Purpose- Carotid artery stenting in tandem large vessel occlusion strokes is usually avoided because of the intracranial hemorrhagic risks induced by antiplatelet therapy during thrombectomy interventions. This study aimed to evaluate the incidence of hemorrhagic transformation following thrombectomy in large vessel occlusion strokes patients with atherosclerotic cervical carotid occlusion, associated factors, and clinical relevance. Methods- The TITAN (Thrombectomy in Tandem Lesions) collaboration pooled individual data of prospectively collected multicentric thrombectomy databases for consecutive anterior circulation tandem large vessel occlusion strokes patients who underwent thrombectomy. Hemorrhagic infarction (HI) and parenchymal hematoma (PH) were assessed within 24 hours. Results- Among 289 patients with atherosclerotic cause, 66 (24.7%) patients developed HI and 38 (14.2%) PH. Intracranial carotid occlusion, diabetes mellitus, absence of prior intravenous thrombolysis, and complete extracranial carotid occlusion were independent predictors of HI. Similar predictors were found for PH with addition of higher baseline National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score <7. No detrimental effect of HI on 90-day clinical outcome was found. The occurrence of PH was associated with increased mortality rates (adjusted odds ratio, 2.63; 95% CI, 1.05-6.59; P=0.039) and had no detrimental effect on 90-day modified Rankin Scale 0 to 2 (adjusted odds ratio, 0.52; 95% CI, 0.20-1.28; P=0.25). Conclusions- Incidence of PH after tandem large vessel occlusion strokes thrombectomy is equivalent to those reported in the literature data for isolated occlusions. Similar predictors were found for PH and HI within 24 hours, whereas acute carotid artery stenting and antiplatelet therapy were not, suggesting an aggressive endovascular treatment of tandem occlusions.

Carotid Stenting With Antithrombotic Agents and Intracranial Thrombectomy Leads to the Highest Recanalization Rate in Patients With Acute Stroke With Tandem Lesions.

OBJECTIVES: The aim of this study was to identify the optimal endovascular approach in patients with acute stroke with tandem lesions. BACKGROUND: At present, there is no consensus about the ideal technical strategy for the endovascular treatment of patients with acute ischemic stroke with tandem lesions of the extracranial internal carotid artery (ICA) and intracranial cerebral arteries. METHODS: This was an international, multicenter registry with a total of 482 patients with acute ischemic stroke and tandem lesions. Patients were treated by intracranial thrombectomy as well as 1 of the following 4 strategies: 1) acute carotid artery stenting of the extracranial ICA with antithrombotic agents; 2) acute carotid artery stenting of the extracranial ICA without antithrombotic agents; 3) balloon angioplasty of the extracranial ICA; and 4) intracranial thrombectomy alone. The main outcome endpoints of the study were the degree of recanalization and the 90-day clinical outcome. The safety endpoints were symptomatic intracerebral hemorrhage and all causes of mortality at 90 days. RESULTS: Using univariate analysis, the rates of successful reperfusion (modified Thrombolysis in Cerebral Infarction grades 2B and 3) and favorable clinical outcome after 90 days were significantly higher after acute carotid stenting with antithrombotic therapy and thrombectomy compared with the group with thrombectomy alone. After adjusting for confounding variables, acute stenting with antithrombotic therapy was independently associated with successful recanalization (odds ratio: 2.4; 95% confidence interval: 1.25 to 4.59; p = 0.008). The rates of symptomatic intracerebral hemorrhage and 90-day mortality were comparable among all 4 treatment groups. CONCLUSIONS: Acute stenting of the extracranial ICA with antithrombotic therapy in combination with intracranial thrombectomy is associated with higher recanalization rates in treatment of patients with acute stroke with tandem lesions.

Acute basilar thrombosis: Recanalization following intravenous thrombolysis is dependent on thrombus length.

INTRODUCTION: We investigated whether thrombus length measured in Computed Tomography Angiography (CTA) is predictive of the success rate of intravenous thrombolysis (IVT) in acute basilar occlusion and whether recanalization can be achieved by additional mechanical endovascular thrombectomy. METHODS: In 51 patients with acute basilar thrombosis thrombus length was measured on CTA images before intravenous thrombolysis (IVT) with rt-PA was started. After 114 minutes on average success of IVT was evaluated either by CTA or DSA. Patients with persistent basilar occlusion and no major brainstem infarction on CT underwent endovascular recanalization. RESULTS: 87% of patients had no recanalization of basilar artery after IVT alone. The average thrombus length was 15 mm in patients with persistent basilar occlusion after IVT and 7 mm in patients with recanalization after IVT. Thrombi longer than 13 mm did not resolve after IVT alone and 80% of thrombi shorter than 13 mm did not resolve either. 41 patients were transferred to endovascular recanalization; endovascular therapy was performed successfully in 90% (37 / 41). CONCLUSIONS: Recanalization rates in acute basilar occlusion after IVT alone are low and dependent on thrombus length. Additional mechanical endovascular thrombectomy showed to be a very successful recanalization therapy.

Projected Numbers of Ischemic Strokes Recorded in the Austrian Stroke-Unit Registry from 2012 to 2075.

BACKGROUND AND PURPOSE: This study analyzed the number of patients with ischemic strokes recorded in the Austrian Stroke-Unit Registry with the aim of projecting this number from 2012 to 2075 and to highlight that the Austrian health system will face a dramatic increase in older patients within the next few decades. METHODS: Current demographic information was obtained from EUROSTAT, and information on age- and sex-stratified 1-year incidence rates of ischemic stroke were obtained from the Austrian Stroke-Unit Registry. Sensitivity analysis was performed by analyzing the projections based on predicted ageing, main, and growth population scenarios, and with stratification by age and gender. RESULTS: The total number of ischemic strokes recorded in the Austrian Stroke-Unit Registry was 8,690 in 2012 and is expected to increase to 15,826, 15,626, or 18,134 in 2075 according to the ageing, main, and growth scenarios, respectively. The corresponding numbers of patients are projected to increase or decrease within different age strata as follows (100%=number of registered ischemic strokes in 2012): 0-40 years, 100%/99% (males/females); 40-50 years, 83%/83%; 50-60 years, 98%/97%; 60-70 years, 126%/119%; 70-80 years, 159%/139%; 80-90 years, 307%/199%; and 90+ years, 894%/413%. CONCLUSIONS: The ageing population in Austria will result in the number of patients increasing considerably from 2012 to 2075, to 182%, 180%, or 208% (relative to 100% in 2012) according to the ageing, main, and growth scenarios, respectively; the corresponding value among those aged 80+ years is 315%, 290%, or 347%. These figures demonstrated the importance of improving primary preventive measures. The results of this study should provide a basis for discussions among health-care professionals and economists to face the future large financial burden of ischemic stroke on the Austrian health system.

Middle cerebral artery aneurysm surgery after stent misplacement: A case report.

Stent misplacement during endovascular treatment of middle cerebral artery (MCA) aneurysms can cause challenges and be problematic, if clipping becomes necessary. This article reports on a 56-year-old woman with an unruptured, multi-lobulated MCA aneurysm, whom primarily refused surgery; therefore, she was scheduled for stent-assisted coiling. After successful deployment of the stent, it unfortunately then became snagged by the microcatheter and was pulled backwards. The subsequent surgical procedure (i.e. clipping of the MCA aneurysm) was challenging, due to the position of the dislodged stent. Such as misplacement of the stent is rarely documented: It resulted in the difficult handling of a MCA aneurysm. Aneurysms of the MCA should primarily be considered for surgical clipping. In conclusion, an increased risk for eventual surgery should be considered, in cases where endovascular treatments with stents are performed.

Latest developments in anticoagulant drug discovery.

Thromboembolic diseases have increased in number over the past years. Oral anticoagulants impair the formation and progression of thrombotic processes and are therefore of great importance in the treatment of these diseases. Until recently, vitamin K antagonists were used to block the coagulation system. But these agents display a lot of interactions besides their narrow therapeutic range and have potential risk of hemorrhage complications. Therefore, other factors of the coagulation cascade are currently being explored as therapeutic targets for the development of novel anticoagulants. This review will provide an overview of new drugs promising more effectiveness in the treatment of arterial and venous embolism. Furthermore, pharmacodynamics and drug interactions regarding new anticoagulants will be reported.

Thrombectomy in patients with large cerebral artery occlusion: a single-center experience with a new stent retriever.

INTRODUCTION: The Trevo device, a new stent retriever, may be utilized in patients with large cerebral artery occlusion. METHODS: Fifty patients with large cerebral artery occlusion and treated with the Trevo device were analyzed. Patients may have received intravenous thrombolysis as a bridging concept in addition to thrombectomy. Outcome and recanalization parameters were documented using the National Institutes of Health Scale, the modified Ranking Scale (mRS) and Thrombolysis in Cerebral Infarction (TICI) score. RESULTS: In all, 82% (95% confidence interval [CI]: 69%-91%) were documented with TICI 2b and 3. Good clinical outcome after 90 days (mRS ≤ 2) was assessed in 61% (95% CI: 46%-75%). Symptomatic intracerebral hemorrhage occurred in 6 patients (12%, 95% CI: 1%-17%). The overall mortality rate was 14% (95% CI: 6%-27%). CONCLUSION: Thrombectomy with the new stent retriever device is feasible and effective and has an acceptable risk of intra-cerebral hemorrhage even in combination with pharmacological revascularization techniques.

Treatment strategies for vasculitis that affects the nervous system.

Vasculitis is a rare but severe disease. It is diagnostically challenging because patients present with nonspecific symptoms. The definitive diagnosis is therefore complicated, because many diagnostic procedures have to be performed. Currently, several systemic types are known that have a secondary affect on the nervous system; an isolated primary central nervous system (CNS) vasculitis also occurs. In this review, we highlight new developments in medical treatment and provide an overview of the various combination strategies regarding the most significant types of vasculitis.

Current therapies in ischemic stroke. Part B. Future candidates in stroke therapy and experimental studies.

Stroke still remains a major healthcare problem. The growing understanding of the mechanism of cell death in ischemia leads to new approaches in stroke treatment. The aim of neuroprotection is to reduce the post-stroke impairment and the overall costs that are accompanied in patients with severe disability. Despite encouraging data from experimental animal models, almost all neuroprotective therapies have, to date, not been established in clinical routine. In this part B of our review on stroke therapies we provide an overview on future candidates in stroke therapy and neuroprotective agents that are under investigation.

Current therapies in ischemic stroke. Part A. Recent developments in acute stroke treatment and in stroke prevention.

Stroke is the third leading cause of death with an increasing prevalence. In previous years many important achievements and new therapeutic strategies have been established. This article provides an overview on recent developments and is an update to the article of Green et al. that was published in 2004. As this article is a comprehensive review we divided it in two parts. In this Part A of our review, recent developments in acute stroke treatment and in stroke prevention are described. In Part B we will reflect on neuroprotection.

Microsurgical venous pouch arterial-bifurcation aneurysms in the rabbit model: technical aspects.

For ruptured human cerebral aneurysms endovascular embolization has become an equivalent alternative to aneurysm clipping.(1) However, large clinical trials have shown disappointing long-term results with unacceptable high rates of aneurysm recanalization and delayed aneurysm rupture.(2) To overcome these problems, animal experimental studies are crucial for the development of better endovascular devices.(3-5) Several animal models in rats, rabbits, canines and swine are available.(6-8) Comparisons of the different animal models showed the superiority of the rabbit model with regard to hemodynamics and comparability of the coagulation system and cost-effectiveness.(9-11) The venous pouch arterial bifurcation model in rabbits is formed by a venous pouch sutured into an artificially created true bifurcation of both common carotid arteries (CCA). The main advantage of this model are true bifurcational hemodynamics.(12) The major drawbacks are the sofar high microsurgical technical demands and high morbidity and mortality rates of up to 50%.(13) These limitations have resulted in less frequent use of this aneurysm model in the recent years. These shortcomings could be overcome with improved surgical procedures and modified peri- and postoperative analgetic management and anticoagulation.(14-16) Our techniques reported in this paper demonstrate this optimized technique for microsurgical creation of arterial bifurcation aneurysms.

Discovery, development and effectiveness of coagulation-inhibiting drugs for stroke therapy.

INTRODUCTION: Stroke is the third leading cause of death in the US and the leading cause of major disability. A large variety of drugs and new therapeutic strategies are the basis for modern stroke therapy. There is scientific evidence for the effectiveness of only a few coagulation-inhibiting drugs for stroke prevention and treatment, but a lot of clinical trials have been conducted or are ongoing in order to gain more scientific data on stroke management and therapy. AREAS COVERED: This paper gives a general overview of modern coagulation-inhibiting drugs discovered and investigated for prevention or acute stroke therapy and offers prospects of future therapy options. EXPERT OPINION: Without the development of more cost-effective future therapies and implementation of extended prevention programs, stroke will remain the leading cause of disability. There is still a strong need for the discovery of novel drug therapies that effectively avoid blood clotting and stroke without increasing the risk of hemorrhage.

MR imaging of hydrogel filament embolic devices loaded with superparamagnetic iron oxide or gadolinium.

INTRODUCTION: We evaluated hydrogel filaments loaded with barium sulphate and either gadolinium or superparamagnetic iron oxide (SPIO) in an effort to develop an embolic material that is visible with fluoroscopic and magnetic resonance imaging. METHODS: Hydrogel filaments were prepared with gadolinium and iron concentrations ranging from 1,500 to 7,500 and 500 to 2,500 ppm, respectively. The filaments were encased in agar and imaged using an MR scanner. Embolisation of eight aneurysms (seven bifurcation, one sidewall) in seven rabbits was performed using hydrogel filaments loaded with gadolinium (n = 4) or SPIO (n = 4). Angiographic evaluations occurred immediately post-treatment and at 13 weeks. Magnetic resonance angiography (MRA) evaluations occurred immediately post-treatment or 13 weeks post-treatment. RESULTS: Based on the in vitro results, we selected 4,500 and 2,000 ppm for gadolinium and iron loadings, respectively, for the in vivo experiments. Loading the filaments with gadolinium or SPIO did not affect the angiographic results, as embolic masses were readily evident with some distinguishing of individual filaments. In MRA, the hydrogel filaments loaded with SPIO were hypointense, and the hydrogel filaments loaded with Gd were hyperintense. The hyperintensity of the Gd-loaded filaments confounded the ability to distinguish between flow and the embolic devices. The hypointensity of the hydrogel filaments loaded with SPIO provided sufficient contrast between the embolic devices and the blood flow to allow of aneurysm occlusion evaluation using MRA. CONCLUSION: Based on these results, we are focusing on loading hydrogel filaments with SPIO in an effort to provide adequate visualisation for use in MR-guided interventions.

Cytokine and growth factor concentration in cerebrospinal fluid from patients with hydrocephalus following endovascular embolization of unruptured aneurysms in comparison with other types of hydrocephalus.

To better understand the development of hydrocephalus of different origins, we evaluated cytokine and growth factor concentration in cerebrospinal fluid from patients with hydrocephalus. CSF was collected from patients developing hydrocephalus following hemorrhage (n = 15), patients with normal pressure hydrocephalus (n = 10), and following the embolization of unruptured intracranial aneurysms (n = 9). Myelography patients (n = 15) served as controls. Quantification of 11 molecules relating angiogenesis, inflammation, and wound healing in the CSF was performed using ELISA. All three hydrocephalus groups had decreased concentration of TIMP-4 compared to the normal group. The hemorrhage group showed increased concentration of IL-6, IL-8, MCP-1, MMP-9, and TIMP-1 compared to the control group. The unruptured aneurysm group had increased concentration of IL-6 and decreased concentration of TIMP-2 compared to the control group. Compared to the normal patients, increased concentrations of wound healing molecules were evident in all three groups. Increased inflammation was evident in the hemorrhage and unruptured aneurysm groups.

Histomorphology of thrombus organization, neointima formation, and foreign body response in retrieved human aneurysms treated with hydrocoil devices.

Biological processes, such as thrombus organization, endothelialization, and foreign body response, that occur following embolization of intracranial aneurysms are poorly understood. We examined 13 human aneurysms (retrieved at autopsy 1-74 days postembolization) treated with hybrid hydrogel-platinum coil devices and platinum coils. The specimens were embedded in methyl methacrylate and ground sections were surface stained. Using light microscopy, thrombus organization in the sac, endothelialization of the neck, and foreign body response to the embolic devices were determined. The area percentages of the sac occupied by embolic devices and unorganized thrombus were quantified using image analysis. Thrombus organization increased over time, but was incomplete up to 74 days post-treatment. Neointima formation had started at 5 days upon dense fibrin depositions and progressed to form a new vessel wall at 74 days. The foreign body response to the hydrogel was characterized by mononuclear macrophages, while platinum coils were surrounded by multinuclear foreign body giant cells. Histometric aneurysm occlusion ranged from 89 to 100% and embolic devices occupied 31-64% of the aneurysm sac. These findings showed that the hydrogel-based devices occupied a large percentage of the aneurysm sac, provided a framework for thrombus organization to occur, and elicited less severe foreign body response than platinum coils.

Current endovascular treatment of acute stroke and future aspects.

Acute ischemic stroke remains a condition of high morbidity and mortality. Until now, the only established therapy has been intravenous (IV) tissue-type plasminogen activator (tPA). Only 3-10% of patients with acute ischemic stroke receive this treatment. On the basis of data from part 3 of the European Collaborative Acute Stroke Study (ECASS III), the time window for beneficial treatment of ischemic stroke with IV tPA has been extended from 3 to 4.5h after the onset of stroke symptoms. Beyond that window of opportunity, and additionally to IV treatment, interventional stroke therapy has assumed an important role for the treatment of acute ischemic stroke. Currently, new promising pharmacological and mechanical treatment options are being established as routine procedures to achieve a further improved outcome for stroke patients.

Angiographic and artefact-free computed tomography imaging of experimental aneurysms embolised with hydrogel filaments.

OBJECTIVES: We compared experimental rabbit carotid bifurcation aneurysms embolised with platinum coils or hydrogel filaments by using digital subtraction angiography (DSA) and computed tomography angiography (CTA). METHODS: Embolisation was performed using platinum coils (n = 2), hydrogel filaments loaded with iodine (n = 3) and hydrogel filaments loaded with barium sulphate (n = 3). In one case, a stent was deployed in the parent vessel to determine the effect of hydrogel filaments on stent visualisation. DSA evaluations occurred immediately post-treatment. CTA evaluations occurred at 0-13 weeks post-treatment. The DSA and CTA images were evaluated for the lack of artefacts and the visibilities of the embolic mass, individual coils and residual flow in the aneurysm sac and neck. RESULTS: The DSA results were largely concordant among the three groups. The embolic masses were readily evident with some individual coils being distinguished. In the aneurysms embolised with hydrogel filaments, visualisation of the individual coils, residual flow and stent with minor or no artefacts was possible using CTA. On the other hand, the beam hardening artefacts precluded analysis of aneurysms embolised with platinum coils. CONCLUSION: CTA-compatible embolic devices could have wide applications in diverse locations throughout the vasculature, particularly in combination with stents or stent grafts.

Comparison of experimental aneurysms embolized with second-generation embolic devices and platinum coils.

PURPOSE: The purpose of the study was to compare the performance of second-generation embolic devices with that of platinum coils in experimental aneurysms. METHODS: Microsurgically constructed bifurcation aneurysms in rabbits were embolized with platinum coils (n = 7), HydroCoils 10 (n = 10), HydroSoft (n = 14) or Cerecyte (n = 6) devices. After 1 month, angiographic occlusion was scored and the aneurysms were histologically evaluated by light microscopy. Continuous and ordinal results were compared using ANOVA/Tukey-Kramer HSD and chi(2) tests respectively. RESULTS: Angiographic occlusion at follow-up was increased in the HydroCoil and HydroSoft groups and decreased in the platinum coil and Cerecyte groups. Fibrovascular tissue was observed in the sac of the Cerecyte group, while mixtures of fibrovascular tissue and fibrinous thrombus were observed in the other three groups. The inflammatory response and endothelialization of the neck were similar in all groups. CONCLUSIONS: Expansile hydrogel devices have led to increased progressive occlusion, while degradable polymer devices led to an increased rate of thrombus organization compared with platinum coils.

Therapy of brain arteriovenous malformations: multimodality treatment from a balanced standpoint.

The three therapeutic modalities for arteriovenous malformation (AVM) treatment (surgery, embolization, and radiotherapy) developed in the past years with specific tools, each tool with its own qualities. Soon after the implementation of embolization for treatment of AVMs, this technique was used in combination with microsurgery; since the development of radiosurgery, treatment algorithms combining embolization with surgery and eventual subsequent radiosurgery, embolization with radiosurgery, or surgery with subsequent radiosurgery have been reported. These different combinations have been in use under the term multimodality treatment for many years, but the algorithms regarding the combination of tools, which tool has priority, and how the risk levels of each tool are assessed shows great variability among institutions. Centers with a surgical background see embolization as a technique to increase surgical feasibility and radiosurgery as a tool to complete subtotal AVM excision. Institutions with an endovascular background embolize AVMs with the aim of maximal occlusion rates and view surgery or radiosurgery as a technique to be used if the goal of total endovascular occlusion cannot be achieved. Radiosurgeons receive patients after incomplete embolization or surgical extirpation or a combination of both.