Efficacy and safety of Apixaban in the treatment of cerebral venous sinus thrombosis: a multi-center study.

Background: Information regarding the safety and efficacy of specific direct oral anticoagulants (DOAC) in the treatment of cerebral sinus and venous thrombosis (CSVT) is scarce. Apixaban is one of the most frequently prescribed DOACs. Therefore, we aimed to compare the safety and efficacy of Apixaban with those of vitamin k antagonists (VKA) in patients with CSVT. Methods: Prospective CSVT databases from seven academic medical centers were retrospectively analyzed. Patients treated with Apixaban were compared to those treated with VKA. Data on demographics, clinical presentations, risk factors, radiological and outcome parameters were studied. Results: Overall, 403 patients were included in the analysis. Of them, 48 (12%) were treated with Apixaban, and 355 (88%) were treated with VKA. Rates of coagulopathies were significantly higher in the VKA-treated patients but no other differences between the groups were found in baseline characteristics and underlying etiology. No significant differences were found between groups in efficacy or safety parameters including the rates of recanalization, favorable outcomes, one-year mortality, seizures, intracranial hemorrhage or CSVT recurrences. Conclusion: Our data suggests that Apixaban may be safe and effective for patients with CSVT. These results should be tested in prospective randomized clinical studies.

Factors influencing real-life use of direct oral anticoagulants in patients with cerebral sinus and venous thrombosis.

BACKGROUND: Direct oral anticoagulants (DOAC) are advocated as equally effective to vitamin K antagonists (VKA) for the treatment of patients with cerebral sinus and venous thrombosis (CSVT). However, data concerning the real-life management practices in CSVT patients are is lacking. METHODS: Prospective CSVT databases from four large academic medical centers were retrospectively studied. Demographics, clinical presentations, risk factors, radiological and outcome parameters were compared between CSVT patients treated with DOAC and VKA. RESULTS: Out of 504 CSVT patients, 43 (8.5%) were treated with DOAC, and the remaining 461 (91.5%) were treated with VKA. All patients with antiphospholipid syndrome (APLA) were treated with VKA (61 vs. 0, p=0.013). Patients with a history or presence of malignancy were also more often treated with VKA (16% vs. 5%, p=0.046). Other risk factors for thrombosis did not differ between the groups. There were no differences in clot extent or location and no differences in the percentage of favorable outcomes or mortality were observed. CONCLUSION: Our data suggests that only malignancy and antiphospholipid antibodies significantly influenced physician's decisions towards choosing VKA rather than DOAC. DOAC appear to be as effective and safe as VKA in patients with CSVT.

Characteristics of Multiple Acute Concomitant Cerebral Infarcts Involving Different Arterial Territories.

(1) Background: Multiple acute concomitant cerebral infarcts (MACCI) are relatively uncommon. Data regarding the characteristics and outcomes of patients with MACCI are lacking. We, therefore, aimed to characterize the clinical features of MACCI. (2) Methods: Patients with MACCI were identified from a prospective registry of stroke patients admitted to a tertiary teaching center. Patients with an acute single embolic stroke (ASES) involving only one vascular bed served as controls. (3) Results: MACCI was diagnosed in 103 patients who were compared to 150 patients with ASES. MACCI patients were significantly older (p = 0.010), more often had a history of diabetes (p = 0.011) and had lower rates of ischemic heart disease (p = 0.022). On admission, MACCI patients had significantly higher rates of focal signs (p < 0.001), an altered mental state (p < 0.001) and seizures (p = 0.036). The favorable functional outcome was significantly less common in patients with MACCI (p = 0.006). In the multivariable analysis, MACCI was associated with lower chances of achieving favorable outcomes (odds ratio: 0.190, 95% CI: 0.070-0.502). (4) Conclusions: There are important differences in clinical presentation, comorbidities and outcomes between MACCI and ASES. MACCI is less often associated with favorable outcomes and could represent a more severe form of a stroke compared with a single embolic stroke.

Characteristics of patients with cerebral sinus venous thrombosis and JAK2 V617F mutation.

OBJECTIVES: Janus kinase 2 (JAK2-V617F) mutations can cause thrombocytosis, polycythemia and hyper viscosity leading to cerebral sinus venous thrombosis (CSVT). However, data regarding the characteristics and prevalence of JAK2-V617F mutation in patients with CSVT are currently lacking. We aimed to evaluate the characteristics of CSVT patients that carry the JAK2 mutation. MATERIALS AND METHODS: Data of consecutive patients with CSVT, admitted to three large academic medical centers between 2010 and 2020, were retrospectively studied. Demographics, clinical presentations, radiological and clinical outcome parameters were compared between carriers of the JAK2-V617F mutation and controls. RESULTS: Out of 404 patients diagnosed with CSVT, 26 patients (6.5%) were carriers of the mutation. JAK2 mutation carriers more often had thrombocytosis (54% vs. 1%, p < 0.001). Furthermore, carriers of the JAK2 mutation less often had involvement of the transverse sinus (50% vs. 68%, p = 0.021). Finally, patients with the JAK2 mutation were more prone to have intracerebral hemorrhage (ICH, 31% vs. 17%, p = 0.044), but there was no significant difference between groups in terms of mortality nor functional outcome. CONCLUSIONS: JAK2 mutation is not uncommon in patients with CSVT and should be routinely screened for in this population. CSVT in JAK2 mutation carriers may have a tendency toward involving specific venous sinuses and is associated with a higher rate of ICH but similar overall prognosis.

Tandem occlusions involving the internal carotid and anterior cerebral arteries-A rare form of stroke: Results from the multicenter EVATRISP collaboration study.

Background: Patients with stroke secondary to isolated anterior cerebral artery (ACA) occlusions have poor outcomes. Whether tandem occlusions (TO) of the extracranial internal carotid (ICA) and the ACA carry even worse outcomes that remain unknown. Methods: Patients with TO involving ICA and ACA occlusions were identified from 14 participating centers from the EndoVascular treatment And ThRombolysis in Ischemic Stroke Patients (EVATRISP) project which is a multicenter, observational, cohort study with prospective accrual of data followed by retrospective data analysis. Patients with isolated ACA stroke served as controls. Results: Included were 92 patients with isolated ACA and 16 patients with ICA-ACA TO stroke. On univariate analyses, patients with TO had more severe strokes on admission [median NIHSS (IQR) 13.5 (9-21) vs. 8 (5-12), p = 0.003] and were more often treated with thrombectomy (81 vs. 40%, p = 0.002). Mortality rates were higher among TO patients (31 vs. 11%, p = 0.03). Rates of favorable functional outcomes were numerically lower among TO patients (38 vs. 60%) but the difference was not statistically significant (p = 0.09). On multivariate analyses, the presence of TO did not modify the chances for favorable outcomes. Conclusion: TO stroke with ICA and isolated ACA involvement is rare and results in more severe initial neurological deficits and higher mortality compared to those seen in patients with isolated ACA stroke.

Safety and Efficacy of Intravenous Alteplase before Endovascular Thrombectomy: A Pooled Analysis with Focus on the Elderly.

Current guidelines advocate intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT) for all patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). We evaluated outcomes with and without IVT pretreatment. Our institutional protocols allow AIS patients presenting early (<4 h from onset or last seen normal) who have an Alberta Stroke Program Early CT Score (ASPECTS) ≥6 to undergo EVT without IVT pretreatment if the endovascular team is in the hospital (direct EVT). Rates of recanalization and hemorrhagic transformation (HT) and neurological outcomes were retrospectively compared in consecutive patients undergoing IVT+EVT vs. direct EVT with subanalyses in those ≥80 years and ≥85 years. In the overall cohort (IVT+EVT = 147, direct EVT = 162), and in subsets of patients ≥80 years (IVT+EVT = 51, direct EVT = 50) and ≥85 years (IVT+EVT = 19, direct EVT = 32), the IVT+EVT cohort and the direct EVT group had similar baseline characteristics, underwent EVT after a comparable interval from symptom onset, and reached similar rates of target vessel recanalization. No differences were observed in the HT frequency, or in disability at discharge or after 90 days. Patients receiving direct EVT underwent more stenting of the carotid artery due to stenosis during the EVT procedure (22% vs. 6%, p = 0.001). Direct EVT and IVT+EVT had comparable neurological outcomes in the overall cohort and in the subgroups of patients ≥80 and ≥85 years, suggesting that direct EVT should be considered in patients with an elevated risk for HT.

Effects in Israel of Arab and Jewish Ethnicity on Intracerebral Hemorrhage.

Intracerebral hemorrhages (ICH) characteristics reportedly differ between different ethnic groups. We aimed to compare the characteristics of Jewish and Arab ICH patients in Israel. Consecutive patients with primary ICH were included in a prospective institutional database. Demographics, vascular risk factors, clinical and radiological parameters were compared between Arab and Jewish ICH patients residing in Jerusalem. The study included 455 patients (311 Jews). Arab patients were younger (66.1 ± 13.4 vs. 72.2 ± 12.2 years, p < 0.001) and had higher rates of diabetes (60% vs. 29%, p < 0.001) and smoking (26% vs. 11%, p < 0.001). Arab patients had higher rates of deep ICH (74% vs. 62%, p = 0.01) and lower rates of lobar ICH (18% vs. 31%, p = 0.003). In a sub-analysis of deep ICH patients only, Arab patients were younger (64.3 ± 12.9 vs. 71.4 ± 11.8 years, p < 0.001) and less frequently male (56% vs. 68%, p = 0.042), with higher rates of diabetes (61% vs. 35%, p < 0.001) and smoking (31% vs. 14%, p < 0.001). In conclusion, the two ethnic populations in Israel differ in the causes and attributes of ICH. Heavy smoking and poorly controlled diabetes are commonly associated with deep ICH in the Arab population and may offer specific targets for secondary prevention in this population.

The Significance of Atrial Fibrillation in Patients With Transient Global Amnesia.

Background and Purpose: The etiology of transient global amnesia (TGA) remains unclear in a large subset of patients. We aimed to determine the clinical and radiological characteristics of TGA-patients with suspected acute micro-embolic stroke on diffusion-weighted imaging (DWI). Methods: TGA-patients that had new DWI hippocampal lesions (DWI+) were compared to DWI negative TGA-patients (DWI-). Demographics, risk factors, clinical data, radiological data, and mortality were analyzed. Results: Out of 83 patients diagnosed with TGA, 56 (65%) underwent MRI during the acute hospitalization and 26 (46%) had new hippocampal DWI lesions. DWI+ patients more often had a history of atrial fibrillation (AF, 26 vs. 7%, p = 0.04) but the frequency of other risk factors did not differ. None of the patients died, however, two DWI+ patients had subsequent stroke during a 2-year follow up and both had AF. In contrast, none of the DWI- patients had recurrent events. Conclusion: AF is common among DWI+ TGA-patients. The presence of AF in patients with TGA could suggest an increased risk of subsequent stroke.

Characteristics of Cerebral Sinus Venous Thrombosis Patients Presenting with Intracerebral Hemorrhage.

Patients with cerebral venous sinus thrombosis (CVST) occasionally present with intracerebral hemorrhage (ICH). In this study, we aimed to identify predictors for ICH in CVST patients. Prospective CVST databases from three academic centers were retrospectively analyzed. CVST patients with and without ICH upon presentation were compared. Among the 404 included patients (mean age 41.8 years, 33% male), 74 (18.3%) had an ICH. The patients with ICH were older (45 ± 20.6 vs. 41.1 ± 18 years, p = 0.045), and were more often pregnant or postpartum women (15% vs. 6%, p = 0.011), or chronically hypertensive (15% vs. 5%, p = 0.001). The ICH patients had higher rates of seizures (60% vs. 15%, p < 0.001), and focal neurological deficits (53% vs. 23%, p < 0.001). The ICH group had lower rates of excellent outcome measured by 90-day mRS 0 (56.7% vs. 80.3%, p < 0.001) and higher rates of 90-day mortality (8% vs. 3%, p = 0.041). Radiological variables associated with ICH included superior sagittal sinus (SSS) thrombosis (63% vs. 36%), isolated cortical vein thrombosis (38% vs. 8%), and presence of venous infarction (34% vs. 7%) (p < 0.001 for all). Upon multivariate analysis, chronic hypertension (OR 3.7, p = 0.027), being either pregnant or postpartum (OR 4.3, p = 0.006), isolated cortical thrombosis (OR 3.5, p = 0.007), and SSS involvement (OR 3.4, p < 0.001) were independently associated with ICH upon admission. In conclusion, among CVST patients, the following present higher for ICH: pregnant or postpartum women, and individuals with chronic hypertension, cortical vein, or SSS involvement.

Characteristics of cerebral sinus venous thrombosis in men.

OBJECTIVES: Cerebral sinus venous thrombosis (CSVT) is a rare stroke subtype that is more common in women, yet data regarding sex-specific characteristics are sparse. We aimed to study male-specific characteristics among patients with CSVT. MATERIALS & METHODS: Data of consecutive patients with CSVT, admitted to a single medical centre between 2005 and 2020, were retrospectively studied. Demographics, clinical presentations, radiological and outcome parameters were compared between male and female patients. Male patients were further divided into older and younger than 35 years old for additional comparisons. RESULTS: Out of 15,224 patients diagnosed with stroke, 150 patients (1%) presented with CSVT and 47 (31.3%) of them were males. Males had significantly higher rates of previous thrombotic events (22% vs. 7%, p = .009), malignancies (32% vs. 16%, p = .022) and Behcet's disease (22% vs. 2%, p < .001). Additionally, we found that malignancies were significantly more prevalent in older males (48% vs. 17%, p = .022), while Behcet's disease was more often found in younger patients (35% vs. 9%, p = .032). Additional age-related differences in disease characteristics among male patients included a higher frequencies of papilledema (42% vs. 13%, p = .028), and cortical vein thromboses (21% vs. 0% p = .021) observed in the younger men. CONCLUSIONS: There are important differences in risk factors for thrombosis between men and women with CSVT. Behcet's disease is common in younger men, while malignancies are major causes of CSVT in older men.

First multicenter experience using the Silk Vista flow diverter in 60 consecutive intracranial aneurysms: technical aspects.

BACKGROUND: The aim of this study was to assess the technical success and procedural safety of the new Silk Vista device (SV) by evaluating the intraprocedural and periprocedural complication rate after its use in several institutions worldwide. METHODS: The study involved a retrospective review of multicenter data regarding a consecutive series of patients with intracranial aneurysms, treated with the SV between September 2020 and January 2021. Clinical, intra/periprocedural and angiographic data, including approach, materials used, aneurysm size and location, device/s, technical details and initial angiographic aneurysm occlusion, were analyzed. RESULTS: 60 aneurysms were treated with SV in 57 procedures. 66 devices were used, 3 removed and 63 implanted. The devices opened instantaneously in 60 out of 66 (91%) cases and complete wall apposition was achieved in 58 out of 63 (92%) devices implanted. In 4 out of 66 (6%) devices a partial opening of the distal end occurred, and in 5 (8%) devices incomplete apposition was reported. There were 3 (5%) intraprocedural thromboembolic events managed successfully with no permanent neurological morbidity, and 4 (7%) postprocedural events. There was no mortality in this study. The initial occlusion rates in the 60 aneurysms were as follows: O'Kelly-Marotta (OKM) A in 34 (57%) cases, OKM B in 15 (25%) cases, OKM C in 6 (10%) cases, and OKM D in 5 (8%) cases. CONCLUSIONS: Our study demonstrated that the use of the new flow diverter Silk Vista for the treatment of intracranial aneurysms is feasible and technically safe.

Are there disparities in acute stroke treatment between the Jewish and Arab populations in Israel? Results from the National Acute Stroke Israeli registry.

BACKGROUND: According to the latest reported data from the National Acute Stroke Israeli Survey (NASIS), around 18,000 strokes occur annually in Israel. Data regarding disparities in stroke care between the Jewish and the Arab populations in Israel are lacking. AIMS: We wished to compare demographics, comorbidities, stroke characteristics and outcomes between Jewish and Arab stroke patients in Israel that were acutely treated with intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT), in order to test if there are disparities or any ethnic-specific parameters. METHODS: The National Acute Stroke Israeli registry of patients undergoing revascularization (NASIS-REVASC) prospectively enrolled patients in six comprehensive stroke centers between 1/2014 and 3/2016. In this observational research, we compared demographics, comorbidities, time metrics, stroke characteristics and outcomes between Jewish and Arab patients enrolled. RESULTS: NASIS-REVASC included 1432 patients out of which 143 (10%) were of Arab ethnicity and 1289 (90%) of Jewish ethnicity. Arab patients were significantly younger (66 ± 14 vs. 73 ± 29, p = 0·004), exhibited higher rates of smoking and diabetes (31% vs. 18% and 57% vs. 34%, p < 0·001 for both), and were less often treated with systemic thrombolysis (48% vs. 59%, p = 0·012). However, the rates of any interventional treatment with either intravenous thrombolysis or endovascular thrombectomy as well as the rates of favorable outcomes and mortality were comparable between groups. CONCLUSIONS: Despite several baseline differences between Arab and Jewish Israeli stroke patients, treatment allocations, survival and functional outcomes were similar indicating lack of disparity in stroke care among patients treated acutely with IVT and/or EVT in Israel. DATA ACCESS STATEMENT: Full data is available following a formal request to the NASIS-REVASC registry at the Israeli Health Ministry.

Post-stroke ASPECTS predicts outcome after thrombectomy.

PURPOSE: Infarct growth and final infarct volume are established outcome modifiers following endovascular thrombectomy (EVT) for patients with large vessel occlusion stroke (LVO). Simple techniques for final infarct volume measurement are lacking, and therefore, we tested whether post-EVT ASPECTS can be used for prognostic evaluation after EVT. METHODS: Infarct size at baseline was measured in a prospective cohort of patients with LVO that underwent EVT with the ASPECTS score on admission non-contrast CT. Final infarct size was assessed with a post-EVT ASPECTS (ASPECTS-POST) obtained from a follow-up CT 24-72 h post-EVT. The best performing ASPECTS-POST was chosen based on comparisons of different thresholds. Outcome measures included survival rates and modified Rankin Score at 90 days. RESULTS: A total of 272 patients were included and 166 of them had an ASPECTS-POST ≥ 7. ASPECTS-POST ≥ 7 was associated with increased likelihood of favorable outcome at 90 days (67% vs. 21%, p < 0.001) with sensitivity, specificity, and positive and negative predictive values of 86%, 58%, 61%, and 85%, respectively. On multivariate analysis, ASPECTS-POST ≥ 7 was found to be a significant modifier of favorable outcome (Odds Ratio [OR] 6.2, 95% confidence intervals [CI] 3.1-12.4) and survival (OR 5.8 95% CI 2.4-14.3). CONCLUSION: ASPECTS can be rapidly and easily obtained from the post-EVT NCCT and ASPECTS-POST ≥ 7 correlates with good outcome.