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Chronic subdural hematoma (cSDH) is caused by rupture of bridging intracranial veins located in the subdural space. Predominantly, cSDH is a disease of older adults and other predisposing risk factors include minor head trauma, cerebral atrophy, antiplatelet and anticoagulation therapies, arterial hypertension, cerebrovascular atherosclerosis, diabetes mellitus, cerebrospinal fluid loss, and excessive alcohol consumption. The incidence of cSDH is rising worldwide due to an aging population and the increased use of anticoagulant or antiplatelet medications. Clinical manifestations are varied, with altered mental status and focal neurologic deficits among the most common.Treatment strategies depend on the symptomatology and extent of hematoma. In general, conservative treatment is sought for patients who are asymptomatic or have only mild symptoms, whereas symptomatic patients are often treated surgically. However, the recurrence rate of cSDH may be as high as 30%. In recent years, middle meningeal artery embolization has emerged as a complementary option to surgery aimed at decreasing the recurrence rate after excision as well as an alternative therapeutic approach to surgical therapy in certain circumstances.Embolization of the middle meningeal artery appears to be a promising treatment for patients with cSDH, both before and after surgical excision.HINTERGRUND: Ein chronisches Subduralhämatom (cSDH) wird durch die Ruptur von intrakranialen Brückenvenen im Subduralraum verursacht. In erster Linie ist das cSDH eine Erkrankung älterer Erwachsener; zu den prädisponierenden Risikofaktoren gehören leichtgradige Kopftraumata, zerebrale Atrophie, Thrombozytenaggregationshemmer- und Antikoagulationstherapie, arterielle Hypertonie, zerebrovaskuläre Arteriosklerose, Diabetes mellitus, Verlust von Liquor cerebrospinalis und exzessiver Alkoholkonsum. Weltweit gibt es einen Anstieg der Inzidenz des cSDH aufgrund einer alternden Bevölkerung und der vermehrten therapeutischen Anwendung von Thrombozytenaggregationshemmern oder Antikoagulanzien. Das klinische Bild variiert, dabei zählen ein veränderter Geisteszustand und fokale neurologische Defizite zu den häufigsten Symptomen.Die Behandlungsstrategie wird in Abhängigkeit von der Symptomatik und dem Ausmaß des Hämatoms festgelegt. Im Allgemeinen wird eine konservative Therapie für Patienten angestrebt, die asymptomatisch sind oder nur leichte Symptome aufweisen, während symptomatische Patienten häufig chirurgisch behandelt werden. Allerdings kann die Rezidivrate des cSDH bis zu 30% betragen. In den letzten Jahren stellte sich die Embolisation der A. meningea media als ergänzende Option zur Operation heraus, die darauf abzielt, die Rezidivrate nach Exzision zu senken, sowie in bestimmten Fällen als alternativer Therapieansatz zur chirurgischen Therapie.Die Embolisation der A. meningea media scheint eine vielversprechende Behandlung für Patienten mit cSDH zu sein, sowohl vor als auch nach der chirurgischen Exzision.

BackgroundOptical coherence tomography (OCT) is an ultra-high resolution real-time intravascular imaging method that is gaining interest in cerebrovascular applications.ObjectiveTo compare, in a rabbit elastase aneurysm model, digital subtraction angiography (DSA) and OCT as diagnostic tools for the assessment of aneurysmal remnants and baseline characteristics of aneurysms after flow diverter (FD) implantation.MethodsWith Institutional Animal Care and Use Committee approval, saccular aneurysms were created in 28 rabbits and treated with Derivo FDs. DSA was performed before, and immediately after, stent implantation. As a follow-up, DSA and OCT were performed 28 days after device implantation.ResultsDSA and OCT were successfully performed in 23 cases. OCT could not be achieved in 5 cases owing to navigational difficulties in the stent lumen with the OCT catheter. Residual aneurysms were significantly more often visible with OCT (18/23 (78%) than with DSA 12/23 (52%), p = 0.031).ConclusionOCT was more sensitive than conventional angiography for the assessment of residual aneurysms at 28 days after FD implantation in an animal model.

Headache is a common symptom during pregnancy and in puerperium that requires careful consideration, as it may be caused by a life-threatening condition. Headaches in pregnant women and women in puerperium are classified as primary or secondary; acute, severe and newly diagnosed headaches should prompt further investigation. We aimed to further characterise the demographic features, symptoms, examination findings, and neuroimaging results of cases of headache during pregnancy and in puerperium. All pregnant women or women in postpartum conditions who attended neurological consultations at the emergency department of the clinic for Gynaecology, Obstetrics and Reproductive Medicine of Saarland University/Germany between 2001/2015 and 2012/2019 were enrolled in this retrospective chart review. Data collected from the charts included demographic/pregnancy characteristics, clinical features and imaging findings. Descriptive statistics as well as binary logistic regression were performed. More than 50% of 97 patients had abnormal findings in their neurological examination. Magnetic resonance imaging findings were pathological for almost 20% of patients—indicating conditions such as cerebral venous thrombosis, reversible posterior leukoencephalopathy, brain tumour and intracranial bleeding. The odds of abnormal neuroimaging results were 2.2-times greater among women with abnormal neurological examination findings than among those with normal examination results. In cases of headache during pregnancy and in puerperium, neuroimaging should be indicated early on. Further research is needed to determine which conditions indicate a need for immediate neuroimaging.

BackgroundRecently, liquid embolic agents have emerged for the endovascular treatment of cerebral aneurysms. Here we describe the in vivo performance of a novel liquid embolization agent (GPX Embolic Device).MethodsElastase-induced aneurysms were embolized with a GPX prototype under balloon assistance. Digital subtraction angiography was performed pre-deployment and immediately after, and at 5, 10, and 30 min post-deployment in 10 rabbits and at 1 month in 8 rabbits. The early post-deployment intra-aneurysmal flow was graded as unchanged, moderately diminished, or completely absent. At 1 month the status of aneurysm occlusion was evaluated. Adhesion to catheter material and migration of GPX was assessed.ResultsThe mean aneurysm neck diameter, width, and height were 3.6±1.0 mm, 3.0±0.8 mm, and 7.4±1.4 mm, respectively. The mean dome-to-neck ratio was 0.9±0.2. Complete stagnation of intra-aneurysmal flow was observed in 9 of 10 aneurysms (90%) within 30 min of device deployment. One aneurysm showed moderately diminished intra-aneurysmal flow at 30 min. At 1 month, 8 aneurysms were completely occluded. There was no evidence of GPX adhesion to the catheter material. Histologically, a leukocyte and foreign body reaction to GPX was detectable 28 days after embolization.ConclusionsThis is the first preclinical study reporting the performance of a protype version of the GPX Embolic Device in a wide-neck aneurysm model. GPX showed promising results by achieving and maintaining high rates of complete angiographic occlusion, but may induce an inflammatory reaction.

Purpose The introduction of flow diverters (FDs) in 2007 greatly enhanced the treatment of intracranial aneurysms. Here, we present our long-term clinical experience in treating unruptured intracranial aneurysms with FDs. Methods 107 patients with unruptured aneurysms and treated with an FD between 2010 and 2019 were retrospectively reviewed. Aneurysm occlusion, procedural complications, and clinical outcome were evaluated. Results Angiographic follow-up was available for 93 patients with a mean long-term follow-up time of 28.4 ± 21.6 months. Additional coiling was performed in 15.1% of patients ( n = 14). Adequate aneurysm occlusion (Kamran grades 3 and 4) at long-term follow-up was achieved in 94.6% of patients ( n = 88). 3.2% ( n = 3) required endovascular retreatment since the last follow-up showed a lack of aneurysm occlusion (Kamran grade 0) due to a foreshortening of the FD. Incomplete opening of the FD and parent vessel occlusion was seen in 1.1% ( n = 1) and 3.2% ( n = 3) of patients, respectively. In-stent stenosis was observed in 57% ( n = 53) of cases at short-term follow-up and 22.6% ( n = 21) at long-term, which were moderate and asymptomatic overall. In-stent stenosis decreased significantly between short- and long-term follow-ups (31.4 ± 17.0% vs 9.7 ± 13.6%, respectively; p ≤ 0.001). Thromboembolic and hemorrhagic events occurred in 7.5% ( n = 7) and 1.1% ( n = 1) of patients, respectively. Good clinical outcome (modified Rankin scale: 0–2) was obtained in 97.8% ( n = 91) leading to an overall treatment-related morbidity of 2.2% ( n = 2). There was no procedural mortality. Conclusion Our study shows that FD treatment of unruptured intracranial aneurysms is effective and safe with high occlusion rates and low rates of permanent morbidity at long-term follow-up.

Background: Altered gastric motility is a frequent non-motor symptom of Parkinson’s disease (PD). It has been hypothesized that disturbed gastric motility contributes to motor fluctuations in PD due to an erratic gastro-duodenal transport and an unpredictable absorption of drugs. Objective: We investigated whether patient-reported fluctuations are associated with parameters of gastric motility visualized by real-time magnetic resonance imaging (MRI) of the stomach. Methods: We analyzed real-time MRI-scans of the stomach after an overnight fasting period in 16 PD patients and 20 controls. MRI was performed 1) in the fasting state, 2) directly after a test meal, and 3) 4 hours postprandially. Gastric motility indices were calculated and compared between groups. Results: MRI showed an attenuated gastric motility in PD patients compared to controls. The difference was most obvious in the early postprandial phase. Gastric motility was not associated with patient-reported motor fluctuations. Using an iron-containing capsule we were able to retrace retention of drugs in the stomach. Conclusion: The results of this study stress the importance of considering the phase of digestion when investigating gastric motility in PD. Despite theoretical considerations, we did not find robust evidence for an association between MRI parameters of gastric motility and patient-reported motor fluctuations. For future studies that aim to investigate gastric motility in PD by MRI, we suggest multiple short-time MRIs to better track the whole gastro-duodenal phase in PD. Such an approach would also allow to retrace the retention of drugs in the stomach as shown by our approach using an iron-containing capsule.

Zusammenfassung Hintergrund Die Therapiestrategie von Patienten mit akutem Schlaganfall der Arteria cerebri media (ACM) wird durch die Lokalisation der Okklusion beeinflusst. Diese Studie zielte darauf ab, die klinischen Ergebnisse bei Patienten mit akutem ischämischem ACM-Verschluss, die mit endovaskulärer mechanischer Thrombektomie (EVT) behandelt wurden, entsprechend dem Okklusionsort zu analysieren. Methoden Es wurden 54 Patienten (Alter: 73 ± 15 Jahre; 59 % weiblich), die aufgrund eines akuten ACM-Verschlusses mittels EVT behandelt wurden, eingeschlossen. In koronar reformatierten MIP-Bildern (Maximumintensitätsprojektion) der CT-Angiographie wurde die Distanz zum Thrombus (DT), also dem Abstand vom Karotis‑T zum Beginn des Thrombus, gemessen. Die Korrelation zwischen DT, klinischer Symptomatik und klinischem Outcome der Patienten mit EVT-Therapie wurde analysiert. Ergebnisse Die DT korrelierte mit der klinischen Symptomatik, gemessen an der National Institutes of Health Stroke Scale (NIHSS; p = 0,017; R = −0,324), bei Aufnahme. Sie korrelierte auch mit der modifizierten Rankin-Skala nach 90 Tagen (90-Tage-mRS; p = 0,014; R = −0,333). Die DT ist ein Prädiktor für ein gutes klinisches Outcome (mRS nach 90 Tagen) nach EVT; Odds-Ratio: 1,113 (p = 0,02; 95 % Konfidenzintervall [KI] 1,017–1,219). Eine DT >10 mm korrelierte signifikant (p = 0,036) mit einem guten klinischen Outcome (90-Tage-mRS ≤2). Schlussfolgerung Die DT korreliert mit der klinischen Symptomatik von Patienten mit akutem ACM-Verschluss. Darüber hinaus sie ein unabhängiger Prädiktor für das klinische Outcome von Patienten, die an einem akuten Schlaganfall durch ACM-Okklusion leiden.

Purpose Mechanical thrombectomy using the Solitaire device has become a standard treatment of ischemic stroke due to large vessel occlusions. Inadvertent detachment is a feared complication, which is associated with poor clinical outcome. The aim of this experimental study was to assess in a porcine model the feasibility and effectiveness of rescuing detached Solitaire devices using different stent retrievers. Methods Solitaire FR devices (4 × 15/20 mm and 6 × 20/30 mm) were placed in the axillary artery of pigs. By means of 3 different stent retrievers (Trevo ProVue; EmboTrap II revascularization device; 3D revascularization device) a total of 24 rescue maneuvers (8 per retriever) were performed by deploying the retrievers within the deployed Solitaire devices and trapping parts of the Solitaire within the microcatheter. Rescue rates, rescue time and complications were assessed. Results Overall stentectomy of the Solitaire devices was successful in all cases (100%). Time of rescue was comparable using the applied stent retrievers (Trevo ProVue; EmboTrap II revascularization device; 3D revascularization device). Complications, such as entrapment of the Solitaire-retriever complex at the intermediate catheter, Solitaire migration, vasospasm, perforation, or dissection were not observed. Conclusion Stentectomy of inadvertently detached Solitaire devices using different stent retrievers is a feasible and effective method. Rescue rates and times with the Trevo ProVue, EmboTrap II and 3D revascularization device were comparable.

Purpose Treatment of wide-necked intracranial aneurysms using the Woven Endobridge (WEB) device has become broadly accepted. Feared complications with the potential of increased poor clinical outcome include dislocations and migration of the device. This study was carried out to determine the effectiveness of a variety of different strategies to rescue migrated WEB devices. Methods In a porcine model, WEB devices of different sizes (SL [single layer] 3.5 × 2mm and SL 4.0 × 3 mm, SL 8 × 5 mm and SLS 8 mm [single layer spherical]) were placed into both the subclavian and axillary arteries. A total of 32 rescue maneuvers (8 per rescue device) were performed. Small WEBs were rescued using reperfusion catheters (RC) (SOFIA Plus and JET 7), larger WEBs were rescued using dedicated rescue devices (Microsnare and Alligator). Rescue rates, times, attempts and complications were assessed. Results Rescue attempts of migrated WEBs were successful in all cases (100%). Rescue time (p = 0.421) and attempts (p = 0.619) of small WEBs using RCs were comparable without significant differences. Aspiration alone was not successful for larger WEBs. Rescue of larger WEBs was slightly faster (122.75 ± 41.15 s vs. 137.50 ± 54.46 s) with fewer attempts (1 vs. 1.37) when using the Microsnare compared to the Alligator device. Complications such as entrapment of the WEB in the RCs, vasospasm, perforation, or dissection were not observed. Conclusion Rescue of migrated WEB devices is a feasible and effective method and 100% successful rescue rates and appropriate rescue times can be achieved for small WEBs using RCs and for larger WEBs using dedicated rescue devices (Microsnare and Alligator).

The development of microstents for aneurysm treatment has greatly expanded endovascular aneurysm therapy. Due to the increased amount of foreign material, the use of such stents is associated with an increased risk of thrombus formation and therewith the associated risk of ischemic stroke. For this reason, various surface coatings have recently been developed. The primary aim of these coatings is to reduce the foreign matter-mediated platelet adhesion to the stent surfaces. The potential reduction of dual antiplatelet therapy when using coated stents was recently discussed. But currently, no neurointerventional guidelines or recommendations endorse the stent implantation under single antiplatelet therapy. This article describes the different coatings in the field of neurointervention and their mode of action.

Due to thromboembolic complications and in-stent-stenosis after flow diverter (FD) treatment, the long-term use of dual antiplatelet treatment (DAPT) is mandatory. The tested nano-coating has been shown to reduce material thrombogenicity and promote endothelial cell proliferation in vitro. We compared the biocompatibility of coated (Derivo Heal) and non-coated (Derivo bare) FDs with DAPT in an animal model. Derivo® bare (n = 10) and Derivo® Heal (n = 10) FD were implanted in the common carotid arteries (CCAs) of New Zealand white rabbits. One additional FD, alternately a Derivo bare (n = 5) or Derivo Heal (n = 5), was implanted in the abdominal aorta (AA) for assessment of the patency of branch arteries. Histopathological examinations were performed after 28 days. Angiography was performed before and after FD implantation and at follow-up. Statistical analysis of the included specimens showed complete endothelialization of all FDs with no significant differences in neointima thickness between Derivo® bare and Derivo® Heal (CCA: p = 0.91; AA: p = 0.59). A significantly reduced number of macrophages in the vessel wall of the Derivo Heal was observed for the CCA (p = 0.02), and significantly reduced fibrin and platelet deposition on the surface of the Derivo Heal was observed for the AA. All branch arteries of the stented aorta remained patent. In this animal model, the novel fibrin-based coated FD showed a similar blood and tissue compatibility as the non-coated FD., Bundesministerium für Wirtschaft und Energie, Projekt DEAL

The introduction of low-profile stent systems has broadened and facilitated the treatment of complex intracranial aneurysms. This retrospective case series study was conducted to assess and compare the clinical and angiographic outcomes of patients with complex intracranial aneurysms who were treated with ACCLINO® (AS) and ACCLINO® flex stents (AFS). In 85 patients (female 61; male 24) a total of 95 complex intracranial aneurysms, 71 (74.7%) in the anterior circulation and 24 (25.3%) in the posterior circulation were treated. Angiographic and clinical data, aneurysm characteristics and follow-up results were analyzed. The AS was used in 47 cases (49.5%) and the AFS in 48 cases (50.5%). Initial angiography after the intervention showed a complete occlusion in 52.6% (Raymond-Roy occlusion classification [RROC] 1), a neck remnant in 38.9% (RROC 2) and an incomplete occlusion in 8.4% (RROC 3). Follow-up (AS: 25.2 ± 15.4 months; AFS: 9.6 ± 8.0 months) revealed an occlusion rate of 70.5% (RROC 1), 27.4% (RROC 2) and 2.1% (RROC 3). There was no statistically significant difference between the initial (p = 0.484) and the follow-up occlusion rate (p = 0.284) when comparing the two devices. Recoiling was performed in 8 cases (8.4%). The overall complication rate was 9.5% with 5 strokes (5.3%), 2 hemorrhages (2.1%), 1 in-stent stenosis (1.1%), 1 stent occlusion (1.1%) and 2 stent thromboses (2.1%). There was no procedure-related mortality. Using the ACCLINO® and ACCLINO® flex stent system is a feasible and effective procedure with an acceptable safety profile. Initial and follow-up angiographic results were satisfactory.

PurposeMechanical thrombectomy (MT) is an effective treatment for patients suffering from acute ischemic stroke. However, recanalization fails in about 16.5% of interventions. We report our experience with unsuccessful MT and analyze technical reasons plus patient-related parameters for failure.MethodsFive hundred ninety-six patients with acute ischemic stroke in the anterior circulation and intention to perform MT with an aspiration catheter and/or stent retriever were analyzed. Failure was defined as 0, 1, or 2a on the mTICI scale. Patients with failing MT were analyzed for interventional progress and compared to patients with successful intervention, whereby parameters included demographics, medical history, stroke presentation, and treatment.ResultsOne hundred of the 596 (16.8%) interventions failed. In 20 cases, thrombus could not be accessed or passed with the device. Peripheral arterial occlusive disease is common in those patients. In 80 patients, true stent retriever failure occurred. In this group, coagulation disorders are associated with poor results, whereas atrial fibrillation is associated with success.The administration of intravenous thrombolysis and intake of nitric oxide donors are associated with recanalization success. Intervention duration was significantly longer in the failing group.ConclusionIn 20% of failing MT, thrombus cannot be reached/passed. Direct carotid puncture or surgical arterial access could be considered in these cases.In 80% of failing interventions, thrombus can be passed with the device, but the occluded vessel cannot be recanalized. Rescue techniques can be an option. Development of new devices and techniques is necessary to improve recanalization rates. Assessment of pre-existing illness could sensitize for occurring complications.

It has been hypothesized that microstents which are used to prevent coil protrusion in the treatment of cerebral aneurysms may have flow diverting and therefore occlusive effects. In a rabbit elastase aneurysm model, we investigated the aneurysm occlusion rate and vessel reaction of a braided Accero stent prototype with porosity in the lower range of other available (non-flow-diverter) microstents.Ten aneurysms were induced the right subclavian artery in New Zealand white rabbits and treated with the Accero stent prototype. In each subject, a second stent was implanted in the abdominal aorta to cover the origins of branch arteries. Angiographic follow-up and explantation of the devices and aneurysms for histological analysis were performed after 3 months (n = 5) and 6 months (n = 5).Grades I ( 50%) and II ( 50%) occlusion rates were observed in 9 (90%) and 1 (10%) of ten aneurysms treated with the stent device. The mean reduction in contrast filling at 6 months was 42.1% (p = .02). Neointima thickness was significantly higher in the subclavian artery than in the abdominal aorta after 3 (p = .03), whereas not after 6 months (p = .1). No cases of inadequate wall apposition, branch artery occlusion or stent thrombosis were observed.The present study showed flow remodelling properties of the device prototype with progredient aneurysm occlusion. A larger in vivo study with induced aneurysm should be done to confirm these results.

Purpose Flow Diverters (FD) have immensely extended the treatment of cerebral aneurysms in the past years. Complete aneurysm occlusion is a process that often takes a certain amount of time and is usually difficult to predict. Our aim was to investigate different syngo iFlow parameters in order to predict aneurysm occlusion. Methods Between 2014 and 2018 patients with unruptured cerebral aneurysms treated with a FD were reviewed. Aneurysm occlusion and complication rates have been assessed. In addition, various quantitative criteria were assessed using syngo iFlow before, after the intervention, and after short and long-term digital subtraction angiography (DSA). Results A total of 66 patients hosting 66 cerebral aneurysms were included in this study. 87.9% (n = 58) aneurysms in the anterior and 12.1% (n = 8) in the posterior circulation were treated. Adequate aneurysm occlusion at long-term follow-up (19.05 ± 15.1 months) was achieved in 90.9% (n = 60). Adequately occluded aneurysm revealed a significantly greater peak intensity delay (PI-D, p = 0.008) and intensity decrease ratio (ID-R, p 100%) after FD implantation resulted in an ID-R Conclusion The applied syngo iFlow parameters were found to be useful in predicting adequate aneurysm occlusion and foresee aneurysm growth, which might indicate the implantation of another FD.

Background Tandem occlusions can complicate medical and endovascular stroke treatment. To identify these occlusions, computed tomography angiography (CTA) represents the best imaging modality. However, CTA is still not initially performed in some patients not admitted directly to stroke centers. Early identification of an additional occlusion of the proximal extracranial internal carotid artery may improve the best suitable treatment strategy. The purpose of this study was to find a valuable threshold of thrombus attenuation in a non-contrast head CT (NCCT) scan to facilitate a safe diagnosis of tandem occlusions. Materials and methods Consecutive patients with acute middle cerebral artery (MCA) occlusions who underwent endovascular treatment were identified from our registry of neuroendovascular interventions. Thrombus attenuations of the affected MCA and contralateral vessel were measured by NCCT. To compare individual baseline blood attenuations, the difference between the thrombus attenuation and the contralateral MCA attenuation (referred to as ΔTM) was calculated. Results Three hundred and twenty-five patients were included. There was a highly significant difference between mean thrombus attenuation with isolated MCA occlusion and additional extracranial internal carotid artery (ICA) occlusion (49.9 ± 8 vs. 56.2 ± 10 Hounsfield units (HU); P Conclusion Despite a significant difference in thrombus attenuation in MCA occlusions with an additional extracranial ICA occlusion compared with isolated MCA occlusions, a relevant threshold of thrombus attenuation was not found.

This study aimed to investigate in vivo two stent technologies, with particular emphasis on thrombogenicity and inflammatory vessel remodeling processes. The micro-stents tested in this study were developed for intracranial aneurysm treatment. In our study twelve, New Zealand white rabbits were divided into two groups: 18 laser-cut stents (LCS) and 18 braided stents (BS) were impanated without admiration of antiplatelet medication. Three stents were implanted into each animal in the common carotid artery, subclavian artery, and abdominal aorta. Digital subtraction angiography was performed before and after stent implantation and at follow-up for the visualization of occurring In-stent thromboembolism or stenosis. The Stents were explanted for histopathological examination at two different timepoints, after 3 and 28 days. Angiographically neither in-stent thrombosis nor stenosis for both groups was seen. There was a progressive increase in the vessel diameter, which was more pronounced for BS than for LCS. We detected a higher number of thrombi adherent to the foreign material on day 3 for BS. On day 3, the neointima was absent, whereas the complete formation observed was on day 28. There was no significant difference between both groups regarding the thickness of the neointima. The in vivo model of our study enabled the evaluation of blood and vessel reactions for two different stent technologies. Differences in vessel dimension and tissue around the stents were observed on day 28. Histological analysis on day 3 enabled the assessment of thrombotic reactions, representing an important complementary result in long-term studies., Projekt DEAL

Background and Purpose: This randomized study aimed to evaluate whether the use of a stroke clock demanding active feedback from the stroke physician accelerates acute stroke management. Methods: For this randomized controlled study, a large-display alarm clock was installed in the computed tomography room, where admission, diagnostic work-up, and intravenous thrombolysis occurred. Alarms were set at the following target times after admission: (1) 15 minutes (neurological examination completed); (2) 25 minutes (computed tomography scanning and international normalized ratio determination by point-of-care laboratory completed); and (3) 30 minutes (intravenous thrombolysis started). The responsible stroke physician had to actively provide feedback by pressing a buzzer button. The alarm could be avoided by pressing the button before time out. Times to therapy decision (primary end point, defined as the end of all diagnostic work-up required for decision for or against recanalizing treatment), neurological examination, imaging, point-of-care laboratory, needle, and groin puncture were assessed by a neutral observer. Functional outcome (modified Rankin Scale) was assessed at day 90. Results: Of 107 participants, 51 stroke clock patients exhibited better stroke-management metrics than 56 control patients. Times from door to (1) end of all indicated diagnostic work-up (treatment decision time; 16.73 versus 26.00 minutes, P P P =0.002), (4) end of computed tomography angiography (14.00 versus 17.17 minutes, P =0.001), (5) end of point-of-care laboratory testing (12.14 versus 20.00 minutes, P P =0.016) were improved. In contrast, door-to-groin puncture times and functional outcomes at day 90 were not significantly different. Conclusions: This study showed that the use of a stroke clock demanding active feedback significantly improves acute stroke-management metrics and, thus, represents a potential low-cost strategy for streamlining time-sensitive stroke treatment.

Purpose The Woven Endobridge device (WEB) has become widely applied for the treatment of intracranial aneurysms. Complications are rare, however, especially dislocations and migrations can potentially increase poor clinical outcome. The aim of this study was to assess the feasibility and effectiveness of rescuing migrated Woven Endobridges using different stent retrievers. Methods In a porcine model, Woven Endobridges of different sizes (SLS 4, SLS 7, SL 5 × 3, SL 4 × 3) were placed into the axillary arteries. By means of two different stent retrievers (Solitaire Platinum and 3D Revascularization Device), a total of 20 rescue maneuvers were performed. For this purpose, the retrievers were deployed distally of the migrated Woven Endobridges. After retracting the stent retrievers partially, the Woven Endobridges were trapped within the microcatheter. Rescue rates, time, attempts and complications were assessed. Results Successful rescue of the migrated Woven Endobridges was observed in all cases (100%). Rescue was slightly faster (177.8 ± 72.8 s vs. 223.4 ± 104.1 s) with fewer attempts (1.5 ± 0.8 vs. 1.8 ± 0.9) when using the 3D Revascularization Device compared to the Solitaire Platinum. However, there were no significant differences (p = 0.327; p = 0.554). Migration of the Woven Endobridges during rescue was seen with both stent retrievers in a comparable frequency (p = 0.642). Further complications, such as entrapment of the stent-retriever–WovenEndobridge-complex at the intermediate catheter, vasospasm, perforation or dissection, were not observed. Conclusions Rescue of migrated Woven Endobridges using stent retrievers is a feasible and effective method. Rescue rates, times and attempts with the Solitaire Platinum and 3D Revascularization Device are comparable with each other.

The development of microstents for aneurysm treatment has greatly expanded endovascular aneurysm therapy. Due to the increased amount of foreign material, the use of such stents is associated with an increased risk of thrombus formation and therewith the associated risk of ischemic stroke. For this reason, various surface coatings have recently been developed. The primary aim of these coatings is to reduce the foreign matter-mediated platelet adhesion to the stent surfaces. The potential reduction of dual antiplatelet therapy when using coated stents was recently discussed. But currently, no neurointerventional guidelines or recommendations endorse the stent implantation under single antiplatelet therapy. This article describes the different coatings in the field of neurointervention and their mode of action.

Background and Purpose— A new generation of carotid artery stents that uses a second micromesh layer to reduce embolic events during carotid artery stenting has recently been introduced. The purpose of this study was to compare acute occlusion rates of these new dual-layer stents with those of single-layer stents in the setting of emergency carotid artery stenting with intracranial mechanical thrombectomy in acute ischemic stroke. Methods— Consecutive patients with acute tandem (intra- and extracranial) lesions of the anterior circulation who were endovascularly treated at our institution were identified from our registry of neuroendovascular interventions. Clinical, angiographic, and neuroimaging data were analyzed. End points included acute occlusions of the carotid stents (within 72 hours after stenting) and symptomatic intracerebral hemorrhage. Results— Forty-seven patients were included. Dual-layer stents (n=20) had a significantly higher rate of acute occlusions than single-layer stents (n=27; 45% versus 3.7%; P =0.001; odds ratio, 21.3; 95% confidence interval, 2.4–188.4). There were no significant differences in the rates of patients who had any antiplatelet or dual antiplatelet medication before admission, in the rates of postinterventional symptomatic intracerebral hemorrhage, the mean National Institutes of Health Stroke Scale scores at admission, or the modified Rankin Scale scores at discharge. Conclusions— The recently introduced dual-layer stents have a higher risk of acute occlusion compared with single-layer stents in the treatment of acute stroke.

PurposeThe Barrel stent is a laser cut stent designed for stent-assisted coil embolization of wide-necked bifurcation or branch aneurysms with a single device, with the purpose of lowering the metal-to-artery ratio and its inherent risk of thromboembolic complications of multiple stents. We report our early experiences with this device in 17 patients in this retrospective single-center analysis.Materials and methods17 consecutive patients who underwent stent-assisted coil embolization of wide-necked bifurcation aneurysms with the Barrel stent were retrospectively identified. We analyzed the feasibility of successful deployment and post-treatment angiographic results. Adverse events, clinical outcome, and angiographic follow-up results were also analyzed.ResultsAneurysms were located in the internal carotid artery (n=3), the middle cerebral artery (n=9), the anterior communicating artery (n=3), and the basilar artery (n=2). In the immediate post-treatment angiography, adequate occlusion (neck remnant or total occlusion) was observed in 16/17 (94.1%) of aneurysms. One patient experienced a transient ischemic attack. No permanent neurologic deficits were observed. 13/17 (76.5%) patients underwent short-term follow-up angiography after 3 months, all of which showed adequate occlusion of the aneurysm.ConclusionsIn this small retrospective single-center analysis we show that stent-assisted coiling with the Barrel stent is a safe and effective option for the endovascular treatment of intracranial wide-necked bifurcation aneurysms.

Background and purposeIn recent years, implantation of flow diverters has emerged as an option for the endovascular treatment of intracranial aneurysms. One complication of treatment with flow diverters is the occurrence of in-stent stenosis, which has been reported to be partially reversible. The purpose of our study was to assess the incidence and dynamics of in-stent stenosis on angiographic short term and long term follow-up after treatment with flow diverters.MethodsA retrospective review of our prospectively maintained database identified all patients with intracranial internal carotid artery (ICA) aneurysms treated by flow diverters at our institution between 2014 and 2017. Clinical charts, procedural data, and angiographic results were reviewed.Results18 patients were included. The mean short term follow-up was 92±19 days and mean long term follow-up was 449±120 days after treatment. No neurologic complications were observed. There was no procedure related mortality. Long term angiographic results showed complete occlusion in 83.3%, neck remnants in 11.1%, and incomplete occlusion in 5.5% of cases. In-stent stenosis was observed in all cases. Mean stenosis improved significantly from 30% on short term follow-up to 12% on long-term follow-up (PConclusionIn-stent stenosis is a common finding on short term follow-up after the treatment with flow diverters but improves over time.

Mechanical thrombectomy with stent retrievers in acute stroke has emerged as the technique with the highest recanalization rate of therapeutic procedures available so far. Recently it was demonstrated that compared to intravenous rTPA alone, mechanical thrombectomy improves outcomes of patients with acute occlusions of intracranial arteries of the anterior circulation in several randomized clinical trials. In this article we will give an overview of the steps required for the thrombectomy procedure.

BACKGROUND AND PURPOSE: Germinal matrix hemorrhage is a frequent complication of prematurity and can be associated with adverse neurodevelopmental outcome, depending on its severity. In addition to parenchymal damage, intraventricular residues of hemorrhage and hydrocephalus MR imaging findings include superficial siderosis. The purpose of this study was to investigate the prevalence and location of superficial siderosis in patients with a history of germinal matrix hemorrhage. MATERIALS AND METHODS: We retrospectively identified patients with a history of germinal matrix hemorrhage who underwent MR imaging in our institution between 2008 and 2016. Imaging was evaluated for the presence and location of superficial siderosis. The presence of subependymal siderosis and evidence of hydrocephalus were assessed. RESULTS: Thirty-seven patients with a history of germinal matrix hemorrhage were included; 86.5% had preterm births. The mean age at the first MR imaging was 386 days (range 2–5140 days). The prevalence of superficial siderosis was 67.6%. Superficial siderosis was detected significantly more often when MR imaging was performed within the first year of life (82.8% versus 12.5%, P < .000). When present, superficial siderosis was located infratentorially in all cases, while additional supratentorial superficial siderosis was detectable in 27%. CONCLUSIONS: Here we report that superficial siderosis is a common MR imaging finding in the first year of life of patients with a history of germinal matrix hemorrhage, but it dissolves and has a low prevalence thereafter. A prospective analysis of its initial severity and speed of dissolution during this first year might add to our understanding of the pathophysiology of neurodevelopmental impairment after germinal matrix hemorrhages.

Spinal perimedullary arteriovenous fistulas (PMAVFs) are rare entities among vascular malformations of the spinal cord. Due to progressive myelopathy, spastic paresis, sensory disturbance, and bowl and bladder dysfunction can be the presenting symptoms. Cervical spinal arteriovenous fistulas (AVFs) are even rarer. These lesions differ from the ones in the thoracolumbar region and have an even wider mode of presentation. We report on a 9-year-old boy with a cervical PMAVF manifesting with headache and vertigo.

Germ cell tumors, which constitute approximately 3-5% of tumors of the central nervous system (CNS), can be subdivided into germinomas, embryonal carcinomas, yolk sac tumors, choriocarcinomas, teratomas and mixed germ cell tumors. The diagnosis of intracranial germ cell tumor is based on the clinical symptoms, detection of tumor markers, such as alpha fetoprotein (AFP) and the beta subunit of human chorionic gonadotropin (beta-hCG) in blood and cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) of the brain and spinal cord, CSF cytology and histology. The diagnosis of a secreting germ cell tumor, i.e. a non-germinoma, can be made by the determination of AFP and hCG as tumor markers. Germinomas are radiosensitive but are equally as sensitive to chemotherapy. Teratomas of the CNS are mostly diagnosed in newborns and infants. The most decisive role in the treatment of teratomas is played by as complete a resection as possible. Chemotherapy and irradiation play a subordinate role.Embryonal tumors, which constitute approximately 15-20% of CNS tumors, include medulloblastomas, primitive neuroectodermal tumors (PNET) of the CNS and the atypical teratoid rhabdoid tumor of the CNS. Medulloblastoma is the most common malignant brain tumor in childhood and adolescence. The incidence peak is the fifth year of life with a male predisposition in a ratio of 1.5:1. Medulloblastomas constitute 12-25% of all pediatric CNS tumors and 30-40% of pediatric tumors of the posterior cranial fossa. At the time of diagnosis evidence of dissemination in the CSF cavity is found in approximately 40% of patients. The extreme cell density makes medulloblastomas hyperdense in computed tomography (CT) and can therefore be differentiated from hypodense astrocytomas. The PNETs are histologically related to medulloblastomas, pineoblastomas, atypical teratoid rhabdoid tumors and peripheral neuroblastomas. They are relatively rare in children constituting less than 5% of supratentorial neoplasms. Patients are mostly clinically conspicuous due to macrocephalus and signs of brain pressure and/or seizures. In native CT the solid components of PNETs show a hyperdensity compared to the surrounding brain parenchyma probably due to the high cell density. Cysts and calcification are often detectable. The survival rate of children with CNS tumors has continuously increased in recent years. When corresponding clinical symptoms appear, such as headache, nausea or vomiting when fasting, all of which are evidence of increased intracranial pressure, MRI should be carried out as quickly as possible. Children should be treated in centers with departments of pediatric oncology and hematology and within the framework of studies.

During endovascular treatment of intracranial aneurysms using coils, migration is a serious complication that increases neurological morbidity. The aim of this experimental study was to assess the effectiveness and complications of retrieving volume coils with different, currently available clot retrievers in a porcine model. Volume coils of three-dimensional (3D) shape and different sizes were placed in the axillary artery of pigs. By means of 4 different clot retrievers (Trevo ProVue; Solitaire FR; 3D-Separator; ERIC) a total of 40 retrieval maneuvers (10 per retriever) were performed by deploying the retrievers within the migrated coils and trying to trap parts of the coils by advancing the microcatheter. Retrieval rates, retrieval duration, retrieval attempts, and complications were assessed. Overall coil retrieval was successful in 31 of 40 cases (77.5%). Retrieval rates using the Trevo ProVue (9/10), Solitaire FR (8/10), and the 3D-Separator (9/10) were higher than when using the ERIC (5/10). Duration of retrieval and retrieval attempts were significantly higher using the ERIC (p < 0.05). Complications like inadvertent deployment were only observed in one case using the Solitaire FR. Additional entrapment of the coil-retriever complex at the intermediate catheter was seen in 9 cases (22.5%). There was no case of vasospasm, perforation, or dissection. Retrieval of migrated volume coils using new-generation clot retrievers is a feasible and effective method. Retrieval rates and duration with the Trevo ProVue, Solitaire FR, and 3D-Separator are superior when compared to the ERIC.

Flow diverters are increasingly being used to treat intracranial aneurysms. This study evaluates occurring complications of flow-diverting devices in the treatment of experimental aneurysms, involving the use of micro-CT and small animal MRI at 9.4 T, in correlation to angiographic and histological findings. We previously published two preclinical studies, in which we assessed two different flow diverters in the treatment of elastase-induced aneurysms. Devices have been implanted across the aneurysm neck as well as in the abdominal aorta. From these studies, a total of 65 devices (prototype FD (n = 30) and Derivo embolization device (n = 35)) additionally underwent micro-CT and MRI after angiographic follow-up and before being histologically examined. The different architectures of both devices were precisely comparable due to high-resolution micro-CT imaging. Micro-CT revealed wire fractures in nine cases (30 %) only with the prototype FD. In three cases (10 %), severe wire fractures correlated with an in-stent stenosis due to intimal hyperplasia. Other complications, like distal stent occlusions and post-stent stenosis, were seen in both groups and verified with both imaging techniques. Osseous metaplasia were correlated to calcifications seen with micro-CT. MRI enabled visualization of the position of the implanted devices relative to the aneurysm and revealed incomplete aneurysm neck coverage with the prototype FD in two cases (6.7 %). Micro-CT and 9.4-T MRI are valid to discover and understand occurring complications of flow diverters in the preclinical phase and can serve as evaluation tools to minimize complication rates of endovascular devices in the future.

Purpose In recent years, flow diverters have provided a promising alternative to treat complex intracranial aneurysms. In this study, we compare a second-generation flow-diverting device (Derivo Embolization Device) with its prototype flow diverter, in the treatment of elastase-induced aneurysms in New Zealand white rabbits. Methods The Derivo Embolization Device is a self-expanding stent consisting of 48 nitinol wires. The device was implanted across the necks of 17 elastase-induced aneurysms in New Zealand white rabbits. One additional device was implanted in the abdominal aorta of each animal covering the origin of lumbar arteries. Follow-up was performed after 3 months (n = 8) and 6 months (n = 9) under continuous double antiplatelet therapy. Statuses of angiographic and histological aneurysm occlusion as well as patency of branch arteries and neointimal growth were evaluated and compared with its prototype flow diverter. Results The Derivo Embolization Device provided advanced visibility and flexibility, which led to more accurate navigation and placement. Complete aneurysm occlusion rates were noted in 15 cases (88 %), respectively, compared with 5 cases (28 %) with the first-generation device (p = 0.001). Neointimal growth and diameter stenosis were significantly less with the Derivo Embolization Device and declining after 6 months follow-up in the abdominal aorta. Extreme device oversizing led to distal occlusion of the parent vessel in three cases. Covered branch arteries remained patent throughout the entire period of observation. Conclusions The Derivo Embolization Device provides excellent occlusion of elastase-induced aneurysms while preserving branch arteries.

In the past years, technical developments have raised recanalization rates of endovascular treatments of intracerebral artery occlusions in acute ischemic stroke. By using stent retrievers, several prospective trials have reported recanalization rates up to 79 % as well as good neurological outcome in up to 58 % of the cases. The degree of the recanalization and the length of the procedure are factors known to influence the clinical outcome of patients treated endovascularly. Yet, still little is known about factors influencing the angiographic results of thrombectomy procedures. The purpose of this study was to investigate whether the use of intermediate catheters affects the angiographic results of thrombectomy procedures in basilar artery occlusions.A total of 47 consecutive patients with acute basilar artery occlusions who underwent endovascular treatment with stent retrievers in our department were retrospectively identified. We analyzed the angiographic data regarding the use of intermediate catheters, the lengths of the procedures, the number of passes of the stent retrievers, the angiographic results, and the site of access to the basilar artery.Recanalization with modified thrombolysis in cerebral infarction (mTICI) ≥ 2b was achieved in 74.5 %. Intermediate catheters were used in 13 cases. The mean length of the procedures was significantly shorter when intermediate catheters were used (44.8 ± 27.6 vs. 70.7 ± 41.4 min, P = .043). There were no significant differences in the number of passes or in the final mTICI scores.The use of intermediate catheters significantly reduces the length of mechanical thrombectomy procedures in acute basilar artery occlusions.

New techniques have substantially raised recanalization rates of mechanical thrombectomy in acute ischemic stroke in the last few years with initial prospective trials reporting good neurological outcome in up to 58 % of the cases. However some recent reports questioning the benefit of endovascular therapy have initiated a discussion about the importance of patient-selection. The purpose of this study was to investigate whether an elongation of the carotid artery affects the angiographic outcome of the recanalization procedure in middle cerebral artery (MCA)-occlusions. The data of 54 patients with occlusions of the M1-segment who underwent mechanical thrombectomy were included. The lengths of the carotid arteries were measured using preinterventional computed tomography (CT)-angiograms. To take individual patient’s height into account these lengths were divided by the length of the spine from the tip of the dens to the bottom of the th3 vertebral body (referred to as carotid-to-spine (CS)-Ratio). Angiographic results were scored according to the modified thrombolysis in cerebral infarction (mTICI)-score. Recanalization with mTICI ≥ 2b was achieved in 83.3 %. The mean CS-Ratio was 1.32 ± 0.13. There was a significant correlation between the CS-Ratio and the age of the patients. There were no significant differences in the CS-Ratios of occlusions that were successfully recanalized and those that were not. Neither were there significant correlations of the CS-Ratio and the length of procedure or the number of deployments of the stentretrievers. In this retrospective analysis we report that carotid elongation does not affect angiographic results of mechanical thrombectomy in acute stroke.

In this study, we analyzed angiographic and histologic aneurysm occlusion of a newly designed flow-diverting device. Visibility and flexibility, as well as occlusions of side branches and neointimal proliferation were also evaluated. Aneurysms were induced in 18 New Zealand white rabbits and treated with a braided, “closed-loop-designed” device of nitinol. Additional devices were implanted in the abdominal aorta to cover the origin of branch arteries. Angiographic follow-ups were performed immediately after placement of the device, after 3 months (n = 9) and 6 months (n = 9). The status of aneurysm occlusion (using a five-point scale) and the patency of branch arteries were assessed. Aneurysm occlusion rates were noted as grade 0 in 2 (11 %), grade I in 1 (6 %), grade II in 1 (6 %), grade III in 9 (50 %), and grade IV in 5 (28 %) of 18 aneurysms, respectively, indicating a complete or near-complete occlusion of 78 % under double antiplatelet therapy. Aneurysm occlusion was significantly higher at 6 months follow-up (P = 0.025). Radiopaque markers provided excellent visibility. Limited device flexibility led to incomplete aneurysm neck coverage and grade 0 occlusion rates in two cases. Distal device occlusions were found in three cases, most likely due to an extremely undersized vessel diameter in the subclavian artery. No case of branch artery occlusion was seen. Intimal proliferation and diameter stenosis were moderate. The tested flow diverter achieved near-complete and complete aneurysm occlusion under double antiplatelet therapy of elastase-induced aneurysms in 78 %, while preserving branch arteries.

Darbepoetin (DPO), an erythropoietin (EPO) derivative, was licensed in 2002 to treat patients with solid tumors suffering from chemotherapy-dependent anemia, although various tumors express EPO to improve vascularization, thus favoring tumor growth and spreading. Therefore, we wanted to investigate direct effects of DPO on the liver tumor cell lines HepG2, SkHep1, Huh-7, AKN1, HCC-T and HCC-M, as well as on primary human hepatocytes (hHeps). DPO (0-40 ng/ml) did not affect viability of hHeps, HepG2, SkHep1, AKN1, HCC-T and HCC-M cells, as determined by Resazurin conversion. However, Huh-7 cells' viability dose-dependently decreased from 5 ng/ml DPO on. Lack of LDH release into culture medium and negative DNA laddering excluded apoptosis or necrosis as the cause for the reduced Resazurin conversion. In Huh-7 cells, DPO increased the expression of p53. Interestingly, Huh-7 cells showed the highest basal TGF-β1 expression as compared to the other cell lines. Upon inhibition of TGF-β1 signaling, DPO no longer reduced viability in Huh-7 cells. On the contrary, co-incubation with TGF-β1 made the other cell lines responsive to DPO. Summarizing our data, we show that DPO reduces the growth of Huh-7 cells by up-regulation of the tumor-suppressor gene p53. This mechanism seems to be dependent on a strong TGF-β expression and corresponding signaling in these cells, as other cell lines became responsive to DPO with TGF-β1 supplementation. The knowledge of this mechanism offers great perspectives for the understanding and treatment of solid liver tumors.

Primary human hepatocytes (hHeps) are still gold standard to perform human drug metabolism studies, but their availability is limited by donor organ scarcity. Therefore, hepatoma cell lines are widely used as alternatives, although their phases I and II drug-metabolizing activities are substantially lower compared with hHeps. The major advantage of these cell lines is immediate availability, standardized culture conditions and unlimited life span. Therefore, the aim of this study was to investigate the drug-metabolizing profile of five human hepatoma cell lines (HepG2, Hep3B, HCC-T, HCC-M and Huh-7) over a culture period of 10 passages. Fluorescent-based assays for seven different cytochrome P450 (CYP) isoforms and seven different phase II enzymes were performed and compared with enzymatic activities of hHeps. CYP activities were much lower in the cell lines (5-15% of hHeps), whereas phase II enzyme activities that are involved in buffering oxidative stress (e.g., Glutathione-S-transferase) reached levels comparable with hHeps. Furthermore, phases I and II enzyme activities in hepatoma cell lines vary strongly during culture time. Interestingly, the most constant results were obtained with Huh-7 cells. Huh-7 cells as well as HCC-T cells exhibited a drug-metabolizing profile closest to hHeps between passages two and four. Toxicity studies with Diclofenac, Paracetamol and Verapamil in both cell lines show dose-response characteristics and EC(50) values similar to hHeps. Therefore, we propose that due to the more consistent results throughout the passages, Huh-7 could be an alternative system to the limitedly available hHeps and frequently used HepG2 cell line in the study of drug metabolism.