Factor XI inhibitors - Rising stars in anti-thrombotic therapy?

The "holy grail" of preventing and treating thrombosis and thromboembolism would be a drug that was highly effective (preventing clots) and at the same time had a low risk of bleeding. From a hemostasiological perspective, the inhibition of factor XI represents a promising target because a reduced level of factor XI protects against thrombosis without significantly increasing the risk of spontaneous bleeding. Currently, three different classes of drugs of factor XI-inhibition are tested. These are (1) monoclonal antibodies (mAbs), (2) so-called synthetic, small molecules and (3) antisense oligonucleotides (ASOs). This article provides a narrative overview of the current status of studies on all three classes of drugs. Tests with mAbs have been conducted primarily in DVT prevention after knee replacement surgery. One large phase 3 study is testing the mAbs Abelacimab in patients with atrial fibrillation. The synthetic, small molecules Asundexian and Milvexian are tested in several phase 3 trials, mainly in patients with non-cardioembolic ischemic stroke. Results can be expected in the coming years. Clinical testing of ASOs to inhibit factor XI are still in their infancies.

Aspiration only versus stent retriever only thrombectomy in basilar artery occlusion: a propensity score-matched analysis of the German Stroke Registry.

BACKGROUND: Endovascular treatment has become the standard care for acute basilar artery occlusion (BAO). Uncertainty persists about the optimal thrombectomy technique. OBJECTIVE: To compare aspiration thrombectomy with stent retriever thrombectomy in patients with BAO in a multicenter real-world patient population. METHODS: We analyzed data from the German Stroke Registry-Endovascular Treatment (GSR-ET). Patients with isolated BAO who underwent either aspiration or stent retriever thrombectomy were compared, including propensity score matching (PSM). The primary outcome measure was the modified Rankin Scale shift analysis at 90 days. Secondary outcomes included symptomatic intracranial hemorrhage (sICH), procedure complications, and metrics. RESULTS: Of 13 082 patients in the GSR-ET, 387 patients (mean age 72.0±13.1 years; 45.0% female) fulfilled the inclusion criteria. The thrombectomy technique was aspiration only in 195 (50.4%) and stent retriever only in 192 (49.6%) patients. Functional outcome did not differ between the groups, either before (common OR (cOR) 0.94; 95% CI 0.64 to 1.38) or after PSM (cOR=1.37; 95% CI 0.90 to 2.09). There was no significant difference in sICH (2.6 vs 5.5%; P=0.231; OR=0.46; 95% CI 0.14 to 1.47), but aspiration thrombectomy demonstrated fewer procedure-related complications (4.6% vs 12.5%; P=0.017), a shorter procedure duration (24 vs 48 min; P<0.001), and higher first pass recanalization rates (75.1% vs 44.8%; P<0.001). CONCLUSIONS: In this study both aspiration and stent retriever thrombectomy showed equal efficacy in terms of functional outcome in patients with BAO. However, procedure complications and metrics might favor aspiration over stent retriever thrombectomy.

IV Thrombolysis With or Without Endovascular Treatment for Suspected Ischemic Stroke in Patients With Intracranial Tumors.

BACKGROUND AND OBJECTIVES: IV thrombolysis (IVT) for suspected ischemic stroke in patients with intracranial neoplasms is off-label. However, data on risks of intracranial hemorrhage (ICH) are scarce. METHODS: In a multicenter registry-based analysis within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration, we assessed frequencies of symptomatic and fatal ICH after IVT for suspected ischemic stroke in patients with intracranial tumors by descriptive statistics and analyzed associations with clinical and imaging characteristics by binary logistic regression. Definition of symptomatic ICH was based on the clinical criteria of the European Cooperative Acute Stroke-II trial including hemorrhage at any site in cranial imaging and concurrent clinical deterioration. RESULTS: Screening data of 21,289 patients from 14 centers, we identified 105 patients receiving IVT; among them were 29 patients (28%) with additional endovascular treatment, with suspected, that is, imaging-based, or histologically confirmed diagnosis of intracranial tumors. Among 104 patients with CT or MRI after IVT available, symptomatic and fatal ICH were observed in 9 and 4 patients (9% and 4%, respectively). Among 82 patients with suspected or confirmed meningioma, symptomatic and fatal ICH occurred in 6 and 3 patients (7% and 4%), respectively. In 18 patients with intra-axial suspected or confirmed primary or secondary brain tumors, there was 1 symptomatic nonfatal ICH (6%). Of 4 patients with tumors of the pituitary region, 2 patients (50%) had symptomatic ICH including 1 fatal ICH (25%). Tumor size was not associated with the occurrence of symptomatic ICH (odds ratio 2.8, 95% CI 0.3-24.8, p = 0.34). DISCUSSION: In our dataset from routine clinical care, we provide insights on the safety of IVT for suspected ischemic stroke in patients with intracranial tumors, a population that is commonly withheld thrombolysis in clinical practice and prospective trials. Except for a potential high risk of symptomatic ICH after IVT in patients with tumors of the pituitary region, frequencies of symptomatic ICH in patients with intracranial tumors in our cohort seem to be in the upper range of rates observed in previous studies within the TRISP cooperation. These results may guide individual treatment decisions in patients with acute stroke and intracranial tumors with potential benefit of IVT.

Incidence and outcome of perforations during medium vessel occlusion compared with large vessel occlusion thrombectomy.

BACKGROUND: Vessel perforation during thrombectomy is a severe complication and is hypothesized to be more frequent during medium vessel occlusion (MeVO) thrombectomy. The aim of this study was to compare the incidence and outcome of patients with perforation during MeVO and large vessel occlusion (LVO) thrombectomy and to report on the procedural steps that led to perforation. METHODS: In this multicenter retrospective cohort study, data of consecutive patients with vessel perforation during thrombectomy between January 1, 2015 and September 30, 2022 were collected. The primary outcomes were independent functional outcome (ie, modified Rankin Scale 0-2) and all-cause mortality at 90 days. Binomial test, chi-squared test and t-test for unpaired samples were used for statistical analysis. RESULTS: During 25 769 thrombectomies (5124 MeVO, 20 645 LVO) in 25 stroke centers, perforation occurred in 335 patients (1.3%; mean age 72 years, 62% female). Perforation occurred more often in MeVO thrombectomy (2.4%) than in LVO thrombectomy (1.0%, p<0.001). More MeVO than LVO patients with perforation achieved functional independence at 3 months (25.7% vs 10.9%, p=0.001). All-cause mortality did not differ between groups (overall 51.6%). Navigation beyond the occlusion and retraction of stent retriever/aspiration catheter were the two most common procedural steps that led to perforation. CONCLUSIONS: In our cohort, perforation was approximately twice as frequent in MeVO than in LVO thrombectomy. Efforts to optimize the procedure may focus on navigation beyond the occlusion site and retraction of stent retriever/aspiration catheter. Further research is necessary in order to identify thrombectomy candidates at high risk of intraprocedural perforation and to provide data on the effectiveness of endovascular countermeasures.

Endovascular therapy in patients with internal carotid artery occlusion and patent circle of Willis.

BACKGROUND: Occlusion of the internal carotid artery (ICA) may extend into the middle or anterior cerebral artery (ICA-T) or be confined to the intracranial (ICA-I) or extracranial segment (ICA-E). While there is excellent evidence for endovascular therapy (EVT) in ICA-T occlusions, studies on EVT in non-tandem ICA-I or ICA-E occlusions are scarce. OBJECTIVE: To characterize EVT-treated patients with ICA-I- and ICA-E occlusion by comparing them with ICA-T occlusions. METHODS: The German Stroke Registry (GSR), a national, multicenter, prospective registry was searched for EVT-treated patients with isolated ICA occlusion between June 2015 and December 2021. We stratified patients by ICA occlusion site: (a) ICA-T, (b) ICA-I, (c) ICA-E. Baseline factors, procedural variables, technical (modified Thrombolysis in Cerebral Infarction (mTICI)), and functional outcomes (modified Rankin scale score at 3 months) were analyzed. RESULTS: Of 13 082 GSR patients, 2588 (19.8%) presented with an isolated ICA occlusion, thereof 1946 (75.2%) ICA-T, 366 (14.1%) ICA-I, and 276 (10.7%) ICA-E patients. The groups differed in age (77 vs 76 vs 74 years, Ptrend=0.02), sex (53.4 vs 48.9 vs 43.1% female, Ptrend<0.01), and stroke severity (median National Institutes of Health Stroke Scale score at admission 17 vs 14 vs 13 points, Ptrend<0.001). In comparison with ICA-T occlusions, both ICA-I and ICA-E occlusions had lower rates of successful recanalization (mTICI 2b/3: 85.4% vs 80.4% vs 76.3%; aOR (95% CI for ICA-I vs ICA-T 0.71 (0.53 to 0.95); aOR (95% CI) for ICA-E vs ICA-T 0.57 (0.42 to 0.78)). In adjusted analyses, ICA-E occlusion was associated with worse outcome when compared with ICA-T occlusion (mRS ordinal shift, cOR (95% CI) 0.70 (0.52 to 0.93)). CONCLUSION: Patient characteristics and outcomes differ substantially between ICA-T, ICA-I, and ICA-E occlusions. These results warrant further studies on EVT in ICA-I and ICA-E patients.

Thrombus migration in ischemic stroke due to large vessel occlusion: a question of time.

BACKGROUND: Thrombus migration (TM) is frequently observed in large vessel occlusion (LVO) ischemic stroke to be treated by endovascular thrombectomy (EVT). TM may impede complete recanalization and hereby worsen clinical outcomes. This study aimed to delineate factors associated with TM and clarify its impact on technical and functional outcome. METHODS: All patients undergoing EVT due to LVO in the anterior circulation at two tertiary stroke centers between October 2015 and December 2020 were included. Source imaging data of all individuals were assessed regarding occurrence of TM by raters blinded to clinical data. Patient data were gathered as part of the German Stroke Registry, a multicenter, prospective registry assessing real-world outcomes. Technical outcome was assessed by modified Thrombolysis in Cerebral Infarction scale (mTICI). Functional outcome was assessed by modified Rankin Scale (mRS) at 3 months. RESULTS: The study consisted of 512 individuals, of which 71 (13.8%) displayed TM. In adjusted analyses, TM was associated with longer time from primary imaging to reassessment in the angio suite (aOR 2.37 (1.47 to 3.84) per logarithmic step) and intravenous thrombolysis (IVT; aOR 4.07 (2.17 to 7.65)). In individuals with IVT, a needle-to-groin time >1 hour was associated with higher odds for TM (aOR 2.60 (1.20 to 5.99)). TM was associated with lack of complete recanalization (aORmTICI3 0.46 (0.24 to 0.90)) but TM did not worsen odds for good clinical outcome (aORmRS≤2_d90 0.89 (0.47 to 1.68)). CONCLUSIONS: TM is associated with IVT and longer time between sequential assessments of thrombus location. Consequently, TM may be of high relevance in patients with drip-and-ship treatment.

Coronary angiography in acute ischemic stroke patients: frequency and determinants of pathological findings in a multicenter cohort study.

BACKGROUND: Myocardial injury as indicated by cardiac troponin elevation is associated with poor prognosis in acute stroke patients. Coronary angiography (CAG) is the diagnostic gold-standard to rule-out underlying obstructive coronary artery disease (CAD) in these patients. However, weighing risks and benefits of coronary angiography (CAG) against each other is particularly challenging, because stroke patients undergoing CAG may have a higher risk for secondary intracranial bleeding. Current guidelines remain vague. Thus, the aim of this study was to analyze frequency of pathological findings of CAG and associated clinical factors. METHODS: We analyzed indications and frequency of CAG performed in acute ischemic stroke patients in clinical routine in two European tertiary care hospitals from 2011 to 2018. All data were obtained retrospectively. Multiple logistic regression analyses were performed to identify variables associated with absence of obstructive coronary artery disease defined as presence of at least one coronary vessel stenosis ≥ 50%. RESULTS: A total of 139 AIS patients underwent CAG. Frequent indications for CAG were suspected acute coronary syndrome (N = 114) or scheduled cardiac surgery (N = 25). Acute coronary stenting was applied in 51/139 patients. Among patients with suspected acute coronary syndrome, no obstructive CAD was found in 27/114 patients. Absence of obstructive CAD was associated with insular cortex lesions, no clinical symptoms for ACS, less than three cardiovascular risk factors, younger age and normal wall motion. CONCLUSION: Several variables suggest absence of CAD in AIS patients and may help in clinical decision making in stroke patients with myocardial injury.

Two simple and rapid methods based on maximum diameter accurately estimate large lesion volumes in acute stroke.

BACKGROUND: We compared two simple and rapid diameter-based methods (ABC/2, od-value) in terms of their accuracy in predicting lesion volume >70 ml and >100 ml. METHODS: In 238 DWI images of ischemic stroke patients from the AXIS2 trial, maximum lesion diameter and corresponding maximum orthogonal diameter were measured. Estimation of infarct volume based on od-value and ABC/2 calculation was compared to volumetric assessments. RESULTS: Accuracy of od-value and ABC/2 was similar for >70 ml (92.0 vs. 87.4) and >100 ml (92.9 vs. 93.3). ABC/2 overestimated lesion volume by 29.9%, resulting in a lower specificity. CONCLUSIONS: Od-value is a robust tool for patient selection in trials.

Clinical significance of acute and chronic ischaemic lesions in multiple cerebral vascular territories.

OBJECTIVES: To investigate the association between acute and chronic ischaemic lesions in a multiple territory lesion pattern (MTLP) detected by 3-Tesla MRI and stroke aetiology, specifically atrial fibrillation-associated stroke. METHODS: We analysed data from the 1000+ study - a prospective, observational 3-Tesla MRI cohort study of consecutively included acute stroke patients. Acute and chronic lesions were detected by DWI and fluid-attenuated inversion recovery, respectively. Observers blinded to clinical data allocated lesions to the right anterior, left anterior or posterior circulation. Lesion pattern was categorised as MTLPa/c when more than one territory was affected by either acute or chronic lesions or as MTLPa when more than one territory was affected by acute lesions alone. RESULTS: Of the 1,000 included patients, an MTLPa/c was found in 43% and MTLPa in 24%. Advanced age (aOR=1.21 per 10 years, 95% CI 1.06-1.39), atrial fibrillation (aOR=1.44, 95% CI 1.06-1.94), aortic arch atherosclerosis (aOR=2.52, 95% CI 1.10-5.77), malignant disease (aOR=1.99, 95% CI 1.25-3.16) and lower estimated glomerular filtration rate (eGFR) (aOR=0.90 per 10 ml, 95% CI 0.84-0.97) were associated with MTLPa/c. Only malignant disease (aOR=2.03, 95% CI 1.27-3.23) and lower eGFR (aOR=0.91 per 10 ml, 95% CI 0.85-0.97) were associated with MTLPa. CONCLUSIONS: An MRI-detected multiple territory lesion pattern of acute and chronic ischaemic lesions is frequent and more often present in older patients and patients with atrial fibrillation, aortic arch atherosclerosis, malignant disease and lower eGFR. Considering not only acute but also chronic ischaemic lesions may facilitate identifying atrial fibrillation-associated or aorto-embolic stroke. KEY POINTS: • Brain imaging with MRI may help to determine the aetiology of stroke. • Of 1,000 stroke patients undergoing 3-Tesla MRI, 43% had acute and chronic ischaemic lesions in multiple cerebral vascular territories. • Atrial fibrillation, aortic arch atherosclerosis and malignant disease were associated with a multiple territory lesion pattern.

Prior antiplatelet therapy is not associated with larger hematoma volume or hematoma growth in intracerebral hemorrhage.

Hematoma volume (HV) and hematoma growth (HG) predict mortality and poor outcome in intracerebral hemorrhage (ICH). While the influence of oral anticoagulation on HV, HG and outcome is well established, the effect of prior antiplatelet therapy (APT) remains uncertain. We retrospectively examined data from all patients with acute, primary ICH, and baseline head CT admitted to our department between January 2005 and February 2014. HV were calculated by ABC/2 method. HG was defined as present if HV increased between baseline and follow-up CT ≥ 30% or ≥ 6 mL. We analyzed the influence of APT on HV, HG, and in-hospital mortality using univariate and multivariate analyses. In addition, we used propensity score matching to assess differences in in-hospital mortality rates. From 668 screened patients, 343 had primary ICH and fulfilled all inclusion criteria. APT was present in 99 patients (29%). Baseline median HV was 16 mL (IQR 6-46). HG occurred in 44 of 160 patients with follow-up CT (28%). In-hospital mortality was 10% (n = 36). APT was associated with older age, a mRS score before admission (pre-mRS) of > 2, and presence of cardiovascular comorbidities. We did not find an association between APT and larger baseline HV (p = 0.32), or HG (OR 0.8, 95% CI 0.4-1.9). After propensity score matching for age, pre-mRS, gender, and cardiovascular comorbidities, APT was not associated with higher in-hospital mortality (OR 1.90, 95% CI 0.85-4.24, p = 0.117). This study did not show a higher risk for larger HV, HG, or in-hospital mortality in primary ICH patients with APT.

Assessment of thrombus length in acute ischemic stroke by post-contrast magnetic resonance angiography.

OBJECTIVES: Post-contrast magnetic resonance angiography (PC-MRA) enables visualization of vessel segments distal to an intra-arterial thrombus in acute ischemic stroke. We hypothesized that PC-MRA also allows clot length measurement in different intracranial vessels. METHODS: Patients with MRI-confirmed ischemic stroke and intracranial artery occlusion within 24 hours of symptom onset were prospectively evaluated. PC-MRA was added to a standard stroke MRI protocol. Thrombus length was measured on thick slab maximum intensity projection images. Clinical outcome at hospital discharge was assessed by modified Rankin Scale (mRS). RESULTS: Thirty-four patients (median age 72 years) presenting with a median National Institutes of Health Stroke Scale score of 11 and a median onset to imaging time of 116 min were included. PC-MRA enabled precise depiction of proximal and distal terminus of the thrombus in 31 patients (91%), whereas in three patients (9%) PC-MRA presented a partial occlusion. Median thrombus length in patients with complete occlusion was 9.9 mm. In patients with poor outcome (mRS ≥3) median thrombus length was significantly longer than in those with good outcome (mRS ≤2;P=0.011). CONCLUSIONS: PC-MRA demonstrates intra-arterial thrombus length at different vessel occlusion sites. Longer thrombus length is associated with poor clinical outcome. CLINICAL TRIAL REGISTRATION: NCT02077582; Results.

[Management of acute ischemic stroke]. / Versorgung des akuten ischämischen Schlaganfalls.

Targets of acute ischemic stroke management include verification of clinical diagnosis, start of basic care and decision-making about specific treatments.Effectiveness of most therapeutic options is time dependent. Time delays within the rescue chain are associated with worse outcome. Trained and multidisciplinary teams on Stroke Unit form the backbone of acute management. Moreover, technical infrastructure influences therapeutic options. Cerebral imaging is pivotal.The following five therapies are evidence-based: treatment on a stroke unit, thrombolysis within 4.5hrs after symptom onset, mechanical recanalization in patients with occlusion of proximal, intracranial arteries, early administration of Aspirin, and hemicraniectomy in patients with so-called malignant infarction.This article describes the necessary diagnostic steps and specific as well as non-specific therapeutic options that compose acute management within the first 72 hours.

In-hospital stroke recurrence and stroke after transient ischemic attack: frequency and risk factors.

BACKGROUND AND PURPOSE: We aimed to assess the risk of recurrent ischemic events during hospitalization for stroke or transient ischemic attack (TIA) with optimal current management and to identify associated risk factors. METHODS: We performed a retrospective analysis of all patients treated for acute ischemic stroke or TIA in 3 stroke units between 2010 and 2013. Recurrent stroke was defined as new persisting (≥24 hours) neurological deficit occurring >24 hours after the index event and not attributable to other causes of neurological deterioration. Cox proportional hazard regression identified risk factors associated with recurrent stroke. RESULTS: The study included 5106 patients. During a median length of stay of 5 days (interquartile range, 4-8), stroke recurrence (or stroke after TIA) occurred in 40 patients (0.8%) and was independently associated with history of TIA, symptomatic carotid stenosis (≥70%), or other determined etiology. Patients with recurrent stroke and other determined etiology had cervical arterial dissection (n=2), primary angiitis of the central nervous system (n=1), giant cell arteritis (n=1), and lung cancer with nonbacterial thrombotic endocarditis (n=1). In patients with initial TIA or minor stroke (National Institutes of Health Stroke Scale ≤5) recurrence was associated additionally with pneumonia after the inciting ischemic event but before stroke recurrence. Patients with initial stroke and aphasia had a lower stroke recurrence rate and there were no recurrences in patients with lacunar stroke. Recurrence was associated with significantly higher in-hospital mortality (17.5% versus 3.1%; P<0.001). CONCLUSIONS: In-hospital stroke recurrence was low with optimal current management. Patients with a history of TIA, severe symptomatic carotid stenosis, or uncommon causes of stroke were at higher risk. Pneumonia was associated with a higher risk of stroke recurrence in patients with initial TIA or minor stroke but not in the overall population studied. Aphasia may bias the detection rate by concealing new neurological symptoms.

Safety of thrombolysis in patients with acute ischemic stroke and cerebral cavernous malformations.

BACKGROUND AND PURPOSE: Data on safety of intravenous thrombolysis with recombinant tissue-type plasminogen activator for acute ischemic stroke in patients with coexisting cerebral cavernous malformations (CCMs) are scarce. We assessed the risk of thrombolysis-associated hemorrhage in these patients. METHODS: We searched our tertiary care hospital thrombolysis register for patients with CCM confirmed by MRI (3 T, Siemens, TimTrio) before thrombolysis for acute ischemic stroke. CCMs were graded into subtypes according to the Zabramski classification on the basis of their MRI appearance. The primary end point was symptomatic intracerebral hemorrhage according to European Cooperative Acute Stroke Study III (ECASS III) criteria. The secondary end point was any parenchymal hemorrhage. RESULTS: In a total of 350 patients (median age, 76 years; interquartile range, 68-84; median National Institutes of Health Stroke Scale score, 8; interquartile range, 5-14; 51.4% women), CCMs were found in 9 patients (2.6%). Seven patients had a single CCM, and 2 patients had multiple CCMs with a total number of 12 CCMs in all patients. The subtype of CCMs was type III in 9 cases and type I in 3 cases. Symptomatic intracerebral hemorrhage occurred in 1 of 9 patients with CCM versus 11 of 341 patients without CCM (P=0.27). Parenchymal hemorrhage occurred in 2 of 9 patients with CCM versus 27 of 341 patients (P=0.17) without CCM. CONCLUSIONS: Given the limitations of our study (mainly low number of patients with CCM), the risk of thrombolysis-associated hemorrhage in patients with CCM remains uncertain. Although our data do not suggest an increased hazard from thrombolysis in patients with CCM, larger studies are necessary to determine definitively the influence of CCMs on parenchymal hemorrhage and symptomatic intracerebral hemorrhage.

Age dependency of successful recanalization in anterior circulation stroke: the ENDOSTROKE study.

BACKGROUND: Clinical outcome after endovascular stroke therapy (EVT) for proximal anterior circulation stroke is often disappointing despite high recanalization rates. The ENDOSTROKE study aims to determine predictors of clinical outcome in patients undergoing EVT. Here we focus on the impact of age and recanalization on proximal middle cerebral artery (M1-MCA) or carotid T occlusion. METHODS: ENDOSTROKE is an investigator-initiated, industrially independent multicenter registry launched in January, 2011, for consecutive patients undergoing EVT for large-vessel stroke. This analysis focuses on patients treated in 11 academic and nonacademic stroke centers with angiographically proven M1-MCA (n = 259) or carotid T occlusion (n = 103). Recanalization was defined as Thrombolysis in Myocardial Infarction (TIMI) score 2 or 3, and in patients with available Thrombolysis in Cerebral Ischemia (TICI) data (n = 309) as TICI scores 2b-3. Good outcome was defined as modified Rankin Scale (mRS) score of 0-2 assessed after 3 months or later. RESULTS: The median age was 68 years (25th and 75th percentiles: 56, 76 years), and the median National Institutes of Health Stroke Scale (NIHSS) score at admission was 16 (13, 19); 41% of the patients had a favorable (mRS scores 0-2), and 59% had an unfavorable (mRS scores 3-6) outcome; 83% reached TIMI 2-3 flow. Independent predictors of good outcome were younger age, lower initial NIHSS scores, TIMI 2/3 recanalization and lower serum glucose levels. Outcome was highly dependent on patients' age: 60% of the patients within the lowest age quartile (range: 18-56 years) experienced good clinical outcome, decreasing stepwise over 47% (57-68 years) and 37% (69-76 years) to 17% in the highest age quartile (77-94 years). The proportion of patients with poor clinical outcome despite TIMI 2/3 recanalization ('futile recanalization') increased dramatically from only 29% in the lowest age quartile over 34% and 40% (2nd and 3rd age quartiles) up to 53% in the highest age quartile. Results were similar in patients with available TICI scores, with 'futile recanalization' rates increasing from 24% to 46% (lowest to highest age quartile). CONCLUSIONS: This study emphasizes the dramatic impact of patients' age on outcome in EVT for M1-MCA or carotid T occlusion, even in the presence of recanalization. Reasons for this age-related decrease in clinically successful recanalization rates urgently need clarification and may comprise patient-related factors (age-related increase in cardioembolic strokes, collateral status, comorbidities) as well as periprocedural issues (tortuous vessel anatomy in the elderly, age-dependent negative impact of general anesthesia in EVT).

Periprocedural aspects in mechanical recanalization for acute stroke: data from the ENDOSTROKE registry.

INTRODUCTION: The ENDOSTROKE registry aims to accompany the spreading use of endovascular stroke treatment (EVT) in academic and non-academic hospitals. This analysis focuses on preprocedural imaging, patient handling and referral, as well as on different treatment modalities in mechanical recanalization. METHODS: Data for this study were from observational registry study in 12 stroke centers in Germany and Austria with online assessment of prespecified variables concerning endovascular stroke therapy. RESULTS: Data from 734 patients undergoing EVT were analyzed. Preferred imaging modality prior to EVT was CT (83 %) and CTA (78 %). In 95 %, EVT was performed under general anesthesia. In 55 % of patients, a combination of intravenous (IV) thrombolysis and EVT was used, followed by pure EVT (25 %), intra-arterial (IA) thrombolysis plus EVT (13 %) and IV + IA thrombolysis plus EVT (7 %). Intrahospital time delay until start of EVT was 91 and 99 min in anterior and vertebrobasilar circulation stroke, respectively. Average duration of EVT was 60 min. Overall thrombolysis in myocardial infarction grade 2/3 recanalization rate was 85 %. Stent retrievers were used in 75 %, being associated with higher recanalization rates than non-stent retrievers. Hemorrhagic complications (symptomatic and asymptomatic) occurred in 12 %. Overall vessel occlusion time was approximately 60 min longer in patients being referred from a primary care hospital for EVT. CONCLUSION: This study gives an overview of procedure-related factors in current EVT practice. It gives estimates on preprocedural imaging modalities, periprocedural handling, and treatment combinations used for EVT. Patient referral for EVT from primary care hospitals is associated with longer vessel occlusion times.

Smoking-thrombolysis paradox: recanalization and reperfusion rates after intravenous tissue plasminogen activator in smokers with ischemic stroke.

BACKGROUND AND PURPOSE: The so-called smoking-thrombolysis paradox of an improved outcome after thrombolysis was first described in smokers with myocardial infarction. We investigated whether reperfusion rates and clinical outcome differ between smokers and nonsmokers with ischemic stroke after intravenous tissue plasminogen activator. METHODS: Consecutive acute ischemic stroke patients, who had magnetic resonance imaging before and 1 day after thrombolysis, were included for analysis. All of the patients received intravenous tissue plasminogen activator within 4.5 hours. Reperfusion was defined as a 75% reduction in perfusion deficit (mean transit time >6 s) after thrombolysis compared with baseline. Magnetic resonance angiography was used to evaluate arterial stenosis and occlusion. Functional outcome was assessed 3 months after stroke using the modified Rankin Score. RESULTS: Of 148 patients, 21.6% were smokers (n=32). Smokers were younger (median, 61 years [SD, 9.4 years] versus 75 years [SD, 11.6 years]; P<0.001), less often women (28% versus 51%; P=0.03), had lower baseline glucose levels (median, 6.2 mmol/L [interquartile range, 5.7-6.8 mmol/L] versus 6.7 mmol/L [interquartile range, 6.1-8.2 mmol/L]; P<0.01) and higher baseline perfusion deficits (median, 53 mL [interquartile range, 13-141 mL] versus 17 mL [interquartile range, 2-66 mL]; P=0.04). In a backward stepwise regression analysis including age, sex, hypertension, glucose, perfusion deficit, and smoking, smoking had an odds ratio of 4 (95% confidence interval, 1-16; P=0.03) for reperfusion and 6 (95% confidence interval, 1-30; P=0.05) for recanalization (regression analysis for recanalization also included localization of arterial occlusion). Smokers had a better outcome (modified Rankin Score=0-2) than nonsmokers (77% versus 55%; P=0.05). CONCLUSIONS: Smoking is independently associated with recanalization and reperfusion, indicating that thrombolytic therapy acts more effectively in smokers; because of small numbers, these results should be considered preliminary. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique Identifier: NCT00715533.

ABCD(2) as a screening tool for cerebral infarction on stroke MRI?

BACKGROUND: The newly proposed transient ischemic attack (TIA) definition demands for MRI exclusion of infarction. Due to limited resources other tools than MRI predicting tissue infarction would be valuable. We hypothesized that ABCD(2) risk score is a valid screening tool for diffusion-weighted imaging (DWI) lesions. METHODS: TIA patients were prospectively enrolled in an observational MRI study to receive acute and follow-up stroke MRI. ABCD(2) scores were calculated, and sociodemographics and risk factors were recorded. RESULTS: One hundred and thirty-two TIA patients were enrolled over nine months. Five patients were excluded due to different diagnosis. Forty-five of the 127 remaining patients showed acute ischemic lesions on DWI. Median ABCD(2) scores for DWI-negative and -positive patients were 4 and 5, respectively. Ordinal, trichotomized and dichotomized ABCD(2) were significantly associated to DWI. Univariate analysis of single score items and other risk factors demonstrated unilateral weakness, duration of symptoms and smoking as predictive for DWI restrictions. In multivariate analysis unilateral weakness remained significant. CONCLUSIONS: High-risk ABCD(2) score due to the impact of hemiparesis is associated with the occurrence of DWI lesions but is still not accurate enough for a reliable differentiation of cerebrovascular events with and without MRI lesions.