Early therapy evaluation of intra-arterial trastuzumab injection in a human breast cancer xenograft model using multiparametric MR imaging.

PURPOSE: To investigate the treatment efficacy of intra-arterial (IA) trastuzumab treatment using multiparametric magnetic resonance imaging (MRI) in a human breast cancer xenograft model. MATERIALS AND METHODS: Human breast cancer cells (BT474) were stereotaxically injected into the brains of nude mice to obtain a xenograft model. The mice were divided into four groups and subjected to different treatments (IA treatment [IA-T], intravenous treatment [IV-T], IA saline injection [IA-S], and the sham control group). MRI was performed before and at 7 and 14 d after treatment to assess the efficacy of the treatment. The tumor volume, apparent diffusion coefficient (ADC), and dynamic contrast-enhanced (DCE) MRI parameters (Ktrans, Kep, Ve, and Vp) were measured. RESULTS: Tumor volumes in the IA-T group at 14 d after treatment were significantly lower than those in the IV-T group (13.1 mm3 [interquartile range 8.48-16.05] vs. 25.69 mm3 [IQR 20.39-30.29], p = 0.005), control group (IA-S, 33.83 mm3 [IQR 32.00-36.30], p<0.01), and sham control (39.71 mm3 [IQR 26.60-48.26], p <0.001). The ADC value in the IA-T group was higher than that in the control groups (IA-T, 7.62 [IQR 7.23-8.20] vs. IA-S, 6.77 [IQR 6.48-6.87], p = 0.044 and vs. sham control, 6.89 [IQR 4.93-7.48], p = 0.004). Ktrans was significantly decreased following the treatment compared to that in the control groups (p = 0.002 and p<0.001 for vs. IA-S and sham control, respectively). Tumor growth was decreased in the IV-T group compared to that in the sham control group (25.69 mm3 [IQR 20.39-30.29] vs. 39.71 mm3 [IQR 26.60-48.26], p = 0.27); there was no significant change in the MRI parameters. CONCLUSION: IA treatment with trastuzumab potentially affects the early response to treatment, including decreased tumor growth and decrease of Ktrans, in a preclinical brain tumor model.

Evaluation of the Significance of Persistent Remnant Filling and Enlargement After Flow Diversion for Intracranial Aneurysms.

BACKGROUND: This study aimed to evaluate the clinical course after flow diversion (FD) treatment with a focus on aneurysms with remnant sac filling, by analyzing angiographic outcomes, aneurysm volume, and clinical events. METHODS: We retrospectively reviewed the medical records of 61 patients who underwent FD for intracranial aneurysms between July 2014 and June 2021. RESULTS: The majority of aneurysms (52.5%) were located in the internal carotid artery, with a median diameter of 16.6 mm and neck size of 9.3 mm. Remnant filling was observed in 17 aneurysms (27.9%) more than 18 months after FD, 10 (16.4%) of these aneurysms underwent enlargement, which occurred only in cases with subtotal filling or entry remnant states. Eleven patients experienced major adverse events, and three exhibited unfavorable functional outcomes. The incidence of major adverse events and unfavorable functional outcomes was significantly higher in the aneurysm enlargement group than that in the no-filling or stable remnant filling groups (P < 0.001). Aneurysmal diameter and the presence of incorporated branches were independent predictors of aneurysm enlargement, while the presence of incorporated branches was the only independent predictor of persistent remnant filling. CONCLUSIONS: Aneurysm enlargement after FD is not uncommon, particularly when the aneurysm is large, has incorporated vessels, or does not undergo occlusion within 12 months, often culminating in major adverse events and unfavorable functional outcomes. In addition to investigating angiographic results, it is necessary to evaluate the changes in aneurysm size and clinical events when assessing the efficacy of FD.

The Impact of age and outcomes of high-risk patients on carotid revascularization.

OBJECTIVES: To validate the accuracy of high-risk criteria for carotid endarterectomy (CEA) and analyze the correlation between age and outcome of CEA and carotid artery stenting (CAS) in risk groups. METHODS: We reviewed a prospectively managed vascular surgery database in a single tertiary referral center, and 2482 internal carotid arteries (ICAs) had undergone carotid revascularization from November 1994 to December 2021. To validate high-risk criteria for CEA, patients were classified as high risk (Hr) and normal risk (Nr). Subgroup analysis was performed with patients older or younger than 75 years to investigate the relationship between age and outcome in each group. Primary endpoints were 30-day outcomes including stroke, death, stroke/death, myocardial infraction (MI), and major adverse cardiovascular events (MACEs). RESULTS: A total of 2345 ICAs in 2256 patients were enrolled. The number of patients in the Hr group was 543 (24%) and the number in the Nr group was 1713 (76%). CEA and CAS were performed on 1384 (61%) and 872 (39%) patients, respectively. The 30-day stroke/death rate was higher with CAS than CEA in both the Hr (1.1% vs. 3.9%, p = 0.032) and Nr (1.2% vs. 6.9%, p < 0.001) groups. In unmatched logistic regression analysis of the Nr group (n = 1778), the rate of 30-day stroke/death (OR, 5.575; 95% CI, 2.922-10.636; p < 0.001) was higher for CAS than CEA. In propensity score matching of the Nr group, the rate of 30-day stroke/death (OR, 5.165; 95% CI, 2.391-11.155; p < 0.001) was also higher for CAS than CEA. In the age <75 subgroup of the Hr group (n = 428), CAS was associated with higher 30-day stroke/death (OR, 14.089; 95% CI, 1.314-151.036; p = 0.029). In the age ≥75 subgroup of the Hr (n = 139), there was no difference in 30-day stroke/death between CEA and CAS. In the age <75 subgroup of the Nr group (n = 1318), 30-day stroke/death (OR, 6.300; 95% CI, 2.797-14.193; p < 0.001) was higher in CAS. In the age ≥75 subgroup of the Nr group (n = 460), 30-day stroke/death (OR, 6.468; 95% CI, 1.862-22.471; p = 0.003) was higher in CAS. CONCLUSIONS: In patients older than 75 years in the Hr group, there were relatively poor 30-day treatment outcomes in both CEA and CAS. Alternative treatment is needed that can expect better outcomes in older high-risk patients. In the Nr group, CEA has a significant benefit compared with CAS, and CEA should be recommended more to these patients.

Vessel Wall Changes on Serial High-Resolution MRI and the Use of Cilostazol in Patients With Adult-Onset Moyamoya Disease.

BACKGROUND AND PURPOSE: The natural course of adult-onset moyamoya disease (MMD) is unknown, and there is no medical treatment that halts its progression. We hypothesized that progressive shrinkage of large intracranial arteries occurs in adult-onset MMD, and that cilostazol inhibits this process. METHODS: Serial high-resolution magnetic resonance imaging (HR-MRI) was performed on 66 patients with MMD: 30 patients received cilostazol, 21 received other antiplatelets, and 15 received no antiplatelets or had poor compliance to them. Serial HR-MRI was performed (interval between MRI scans: 29.67±18.02 months, mean±SD), and changes in outer diameter, luminal stenosis, and vascular enhancement were measured. Factors affecting HR-MRI changes were evaluated, including vascular risk factors and the ring finger protein 213 gene variant. RESULTS: The progression of stenosis to occlusion, recurrent ischemic stroke, and the development of new stenotic segments were observed in seven, seven, and three patients, respectively. Serial HR-MRI indicated that the degree of stenosis increased with negative remodeling (outer diameter shrinkage). Patients who received cilostazol presented significantly larger outer diameters and lower degrees of stenosis compared with other groups (p=0.005 and p=0.031, respectively). After adjusting for clinical and genetic factors, only cilostazol use was independently associated with negative remodeling (odds ratio=0.29, 95% confidence interval=0.10-0.84, p=0.023). While vascular enhancement was observed in most patients (61 patients), the progression of enhancement or the occurrence of new vascular enhancement was rarely observed on follow-up HR-MRI (6 and 1 patients, respectively). CONCLUSIONS: Adult-onset MMD induces progressive shrinkage of large intracranial arteries, which cilostazol treatment may prevent. Further randomized clinical trials are warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02074111.

Surgical Strategy for Ethmoidal Dural Arteriovenous Fistula.

OBJECTIVE: Ethmoidal dural arteriovenous fistula (DAVF) is a rare type of intracranial DAVF. The aim of this study was to report our experience with a unilateral approach and discuss its effectiveness for ethmoidal DAVF treatment. METHODS: The study included 19 patients who underwent surgical treatment for ethmoidal DAVF between January 1999 and May 2021. RESULTS: Median age of patients was 59.7 years; 16 (84%) patients were male. Three patients had a ruptured ethmoidal DAVF. Preoperative digital subtraction angiography showed that all ethmoidal DAVFs were supplied by the bilateral external carotid artery branches. In 18 (95%) patients, cortical draining veins were located on the unilateral side. Bilateral lesions were identified in only 1 (5%) patient. The frontobasal approach was performed in 5 patients (26%), the pterional approach was performed in 5 (26%) patients, and the lateral supraorbital approach was performed in 9 (47%) patients; median procedural times were 198 minutes, 172 minutes, and 111 minutes, respectively. Cortical draining vein was successfully disconnected in all 19 patients with 20 ethmoidal DAVFs. Complete obliteration of ethmoidal DAVF was confirmed in all patients, with no postoperative complications. No recurrence or related clinical events were reported in 13 (68%) patients over 12 months of clinical and radiological follow-up. CONCLUSIONS: We reconfirmed excellent outcomes of surgical treatment for ethmoidal DAVFs. Three different surgical strategies were attempted, and each had pros and cons. The lateral supraorbital approach is an efficient surgical option for unilateral ethmoidal DAVFs. Careful preoperative examination for the presence of bilateral drainage is essential.

Significance of D-Dimer in Acute Ischemic Stroke Patients With Large Vessel Occlusion Accompanied by Active Cancer.

Background: This study aimed to investigate clinical outcome predictors of acute stroke patients with large vessel occlusion and active cancer and validate the significance of D-dimer levels for endovascular thrombectomy decisions. Methods: We analyzed a prospectively collected hospital-based stroke registry to determine clinical EVT outcomes of acute stroke patients within 24 h with following criteria: age ≥18 years, NIHSS ≥6, and internal carotid artery or middle cerebral artery lesion. All patients were classified into EVT and non-EVT groups. Patients were divided into two groups by initial D-dimer level. We explored variables potentially associated with successful recanalization as well as 3-month functional outcomes and mortality rates. Results: Among 68 patients, 36 were treated with EVT, with successful recanalization in 55.6%. The low D-dimer group showed a higher rate of successful recanalization and favorable outcome than the high D-dimer group. The mortality rate was higher in the high D-dimer group. No EVT and high D-dimer level were independent predictors of mortality, whereas lesion volume and low D-dimer level were independently associated with favorable outcomes. Conclusions: D-dimer level is a prognostic factor in acute LVO stroke patients with active cancer, and its high value for EVT decisions provisionally supports its testing in this patient population.

Early clinical experience of using the Surpass Evolve flow diverter in the treatment of intracranial aneurysms.

PURPOSE: Here, we presented our early experience with flow diversion procedures using the Surpass Evolve flow diverter (SE, Stryker) and reported the feasibility and safety profile compared to those of a control group treated with other types of flow diverters. METHODS: We included 31 and 53 consecutive flow diversion procedures performed using the SE and other commercial flow diverters, respectively, to treat intracranial aneurysms at our institution. We used two commercial flow diversion systems in the comparison group: the pipeline embolization device and Surpass Streamline. RESULTS: In the SE group, technical failures occurred in three (9.7%) cases, due to either incomplete wall apposition (n = 1, 3.2%) or stent migration (n = 2, 6.5%). Major complications occurred in four (12.9%) cases: delayed rupture of the target aneurysm (n = 1, 3.2%), major ischemic stroke (n = 1, 3.2%), sudden death from an unidentified cause (n = 1, 3.2%), and parent artery occlusion with stent thrombosis (n = 1, 3.2%). Balloon angioplasty was performed in eight (25.8%) cases. On post-procedure MRI, a DWI-positive lesion was detected in three (9.7%) cases. After multivariate adjustment, the SE group was independently associated with less procedural time of ≥ 90 min (adjusted OR, 0.09; 95% CI, 0.03-0.29; p < 0.001), balloon angioplasty (adjusted OR, 0.22; 95% CI, 0.07-0.75; p = 0.015), and DWI-positive lesions (adjusted OR, 0.04; 95% CI, 0.01-0.19; p < 0.001). CONCLUSION: The SE is safe and easy to deploy.

TAB-TICI Score: Successful Recanalization Score After Endovascular Thrombectomy in Acute Stroke.

Background and Purpose: Successful reperfusion therapy is supposed to be comprehensive and validated beyond the grade of recanalization. This study aimed to develop a novel scoring system for defining the successful recanalization after endovascular thrombectomy. Methods: We analyzed the data of consecutive acute stroke patients who were eligible to undergo reperfusion therapy within 24 h of onset and who underwent mechanical thrombectomy using a nationwide multicenter stroke registry. A new score was produced using the predictors which were directly linked to the procedure to evaluate the performance of the thrombectomy procedure. Results: In total, 446 patients in the training population and 222 patients in the validation population were analyzed. From the potential components of the score, four items were selected: Emergency Room-to-puncture time (T), adjuvant devices used (A), procedural intracranial bleeding (B), and post-thrombectomy reperfusion status [Thrombolysis in Cerebral Infarction (TICI)]. Using these items, the TAB-TICI score was developed, which showed good performance in terms of discriminating early neurological aggravation [AUC 0.73, 95% confidence interval (CI) 0.67-0.78, P < 0.01] and favorable outcomes (AUC 0.69, 95% CI 0.64-0.75, P < 0.01) in the training population. The stability of the TAB-TICI score was confirmed by external validation and sensitivity analyses. The TAB-TICI score and its derived grade of successful recanalization were significantly associated with the volume of thrombectomy cases at each site and in each admission year. Conclusion: The TAB-TICI score is a valid and easy-to-use tool to more comprehensively define successful recanalization after endovascular thrombectomy in acute stroke patients with large vessel occlusion.

Identification of de novo EP300 and PLAU variants in a patient with Rubinstein-Taybi syndrome-related arterial vasculopathy and skeletal anomaly.

Rubinstein-Taybi syndrome (RSTS) is a human genetic disorder characterized by distinctive craniofacial features, broad thumbs and halluces, and intellectual disability. Mutations in the CREB binding protein (CREBBP) and E1A binding protein p300 (EP300) are the known causes of RSTS disease. EP300 regulates transcription via chromatin remodeling and plays an important role in cell proliferation and differentiation. Plasminogen activator, urokinase (PLAU) encodes a serine protease that converts plasminogen to plasmin and is involved in several biological processes such as the proteolysis of extracellular matrix-remodeling proteins and the promotion of vascular permeability and angiogenesis. Recently, we discovered a patient who presented with RSTS-related skeletal anomaly and peripheral arterial vasculopathy. To investigate the genetic cause of the disease, we performed trio whole genome sequencing of the genomic DNA from the proband and the proband's parents. We identified two de novo variants coined c.1760T>G (p.Leu587Arg) and c.664G>A (p.Ala222Thr) in EP300 and PLAU, respectively. Furthermore, functional loss of EP300a and PLAUb in zebrafish synergistically affected the intersegmental vessel formation and resulted in the vascular occlusion phenotype. Therefore, we hypothesize that the de novo EP300 variant may have caused RSTS, while both the identified EP300 and PLAU variants may have contributed to the patient's vascular phenotype.

Treatment Outcomes After Single-Device Flow Diversion for Large or Giant Aneurysms.

OBJECTIVE: We aimed to evaluate the efficacy and safety of single-device flow diversion in patients with aneurysms measuring ≥15 mm in diameter. METHODS: For this retrospective study, we extracted medical record data for patients with unruptured intracranial aneurysms, who underwent flow diversion, at the authors' institution between July 2014 and August 2019. The primary effectiveness outcome was defined as angiographic occlusion of the target aneurysm within 18 months without major (>50%) parent artery stenosis, major adverse events, or additional treatment. RESULTS: Thirty-five aneurysms in 35 patients were analyzed. Most aneurysms (n = 29, 82.9%) involved the anterior circulation. The median aneurysmal diameter was 18.3 mm, and the median neck size was 7.6 mm. Eleven (31.4%) aneurysms were considered giant (≥25 mm). The primary effectiveness outcome was achieved in 20 (57.1%) patients at a median of 10 months (interquartile range, 4.3-12.5) after flow diversion. Major adverse events occurred in 6 (17.1%) patients, including remote intraparenchymal hemorrhages (n = 2), a major ischemic stroke (n = 1), a delayed rupture of the target aneurysm (n = 1), and clinical deterioration caused by aggravated mass effect (n = 2). Multivariate logistic regression analysis found 2 independent predictors of the primary effectiveness outcome: the aneurysmal diameter (odds ratio, 0.71; 95% confidence interval, 0.54-0.86; P = 0.004) and the parent-vessel angle (odds ratio, 0.97; 95% confidence interval, 0.93-0.99; P = 0.017). CONCLUSIONS: Single-device flow diversion was shown to be ineffective for large or giant intracranial aneurysms with a high parent vessel angle.

How Cerebral Vessel Tortuosity Affects Development and Recurrence of Aneurysm: Outer Curvature versus Bifurcation Type.

BACKGROUND AND PURPOSE: Previous studies have assessed the relationship between cerebral vessel tortuosity and intracranial aneurysm (IA) based on two-dimensional brain image analysis. We evaluated the relationship between cerebral vessel tortuosity and IA according to the hemodynamic location using three-dimensional (3D) analysis and studied the effect of tortuosity on the recurrence of treated IA. METHODS: We collected clinical and imaging data from patients with IA and disease-free controls. IAs were categorized into outer curvature and bifurcation types. Computerized analysis of the images provided information on the length of the arterial segment and tortuosity of the cerebral arteries in 3D space. RESULTS: Data from 95 patients with IA and 95 controls were analyzed. Regarding parent vessel tortuosity index (TI; P<0.01), average TI (P<0.01), basilar artery (BA; P=0.02), left posterior cerebral artery (P=0.03), both vertebral arteries (VAs; P<0.01), and right internal carotid artery (P<0.01), there was a significant difference only in the outer curvature type compared with the control group. The outer curvature type was analyzed, and the occurrence of an IA was associated with increased TI of the parent vessel, average, BA, right middle cerebral artery, and both VAs in the logistic regression analysis. However, in all aneurysm cases, recanalization of the treated aneurysm was inversely associated with increased TI of the parent vessels. CONCLUSIONS: TIs of intracranial arteries are associated with the occurrence of IA, especially in the outer curvature type. IAs with a high TI in the parent vessel showed good outcomes with endovascular treatment.

White matter hyperintensity determines ischemic stroke severity in symptomatic carotid artery stenosis.

INTRODUCTION: The aim of this study is to investigate the influence of white matter hyperintensity (WMH) on stroke severity and prognosis in patients with symptomatic carotid artery stenosis. METHODS: Patients with symptomatic carotid artery stenosis were retrieved from the Samsung Medical Center stroke registry from January 2011 to December 2016. Stroke severity was categorized into three levels according to National Institutes of Health Stroke Scale (NIHSS): transient ischemic attack (TIA) or transient symptoms with infarction (TSI), mild stroke, and moderate to severe stroke. WMH volume was measured with medical image processing and visualization. The clinical outcome was assessed using the modified Rankin scale on the 90th day from which the latest onset of the neurological symptom. Logistic regression was used to predict stroke severity, and ordinal regression was used to compare the clinical outcome. RESULTS: Among 158 patients, the numbers of patients with TIA or TSI, mild stroke, and moderate to severe stroke were 48 (30.4%), 59 (37.3%), and 51 (32.3%), respectively. The larger WMH volume was associated with moderate to severe strokes (TIA/TSI vs. moderate to severe strokes, odds ratio (OR) 2.318, 95% confidence interval (CI) 1.194-4.502, p = 0.007; mild vs. moderate to severe strokes, OR 1.972, 95% CI 1.118-3.479, p = 0.013). Patients with larger volume of WMH showed poorer clinical outcome (cutoff value: 9.71 cm3, OR 2.099, 95% CI 1.030-4.311, p = 0.042). CONCLUSION: Our study showed that larger WMH volume is associated with more severe stroke and poorer prognosis in patients with symptomatic carotid artery stenosis.

Diffuse Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage in a 15-Year-Old Girl: A Case Report.

Diffuse cerebral vasospasm after subarachnoid hemorrhage (SAH) is a complication resulting in an ischemic condition presenting with altered mentality and followed by motor or speech impairment. It is uncommon in pediatric population and requires differential diagnosis from Moyamoya disease, which is relatively common in Korea. We report a case of a 15-year-old girl who was presented with a seizure and subsequent headache, poor oral intake, and altered mentality, who was finally diagnosed with sporadic vasospasm followed by multiple aneurysm ruptures. The patient had recurrent seizures and persistent headache at the time of transfer. On the second day after transfer, she showed focal motor weakness and dysarthria, and her symptoms gradually progressed, showing paraplegia and aphasia on the third hospitalization day. Brain magnetic resonance imaging and magnetic resonance angiography demonstrated diffuse narrowing cerebral vasospasm of bilateral middle cerebral arteries, anterior cerebral arteries, and distal internal carotid arteries and three unruptured aneurysms. The patient was treated with intravenous hydration and nimodipine to expand the narrowed vessels. After confirming that the vessels were enlarged, we successfully executed the endovascular coil embolization. Her neurological deficits were improved through medical, interventional, and rehabilitation treatments and fully restored 11 months after discharge.

Perfusion recovery on TTP maps after endovascular stroke treatment might predict favorable neurological outcomes.

OBJECTIVES: Early recanalization and adequate collateral blood flow are surrogates for functional recovery in endovascular stroke treatment (EVT). We evaluated the prognostic value of pre- and immediate post-thrombectomy perfusion-weighted magnetic resonance imaging (PWI) parameters. METHODS: Consecutive patients with acute ischemic stroke who underwent EVT were enrolled. Lesion volumes and their corresponding changes on diffusion-weighted (DWI) and PWI were assessed. Outcome was measured with modified Rankin Scale (mRS) at 90 days, and early neurological improvement (> 8 points improvement on National Institutes of Health Stroke Scale [NIHSS] or 0 to 1) at 7 days. RESULTS: Fifty-two patients were enrolled. After control of initial NIHSS and recanalization status, post-thrombectomy time-to-peak (TTP) hypoperfused volume and TTP hypoperfused volume change remained independent predictors of favorable functional outcome (odds ratio [OR] = 0.13, 95% confidence interval [CI] = 0.03-0.54, p = 0.005; OR = 1.018, 95% CI = 1.00-1.03, p = 0.017), and early neurological improvement (OR = 0.20, 95% CI 0.07-0.58, p = 0.003; OR = 1.02, 95% CI = 1.00-1.03, p = 0.010). The areas under the curve of post-thrombectomy TTP hypoperfused volume and TTP hypoperfused volume change were 0.90 and 0.82 (cutoff 68 mL and 56 mL) for favorable outcome and 0.86 and 0.82 (cutoff 76 mL and 58 mL) for early neurological improvement, which had better prognostic values than other MR parameters and recanalization grades. CONCLUSIONS: These results suggest a large amount of perfusion recovery on TTP is associated with favorable outcome as well as early neurological improvement after EVT, and may be a useful prognostic marker. KEY POINTS: • A large amount of perfusion recovery on TTP map is associated with favorable outcome and early neurological improvement after EVT. • The best cutoff value for favorable functional outcome was 68 mL for post-EVT TTP hypoperfused volume and 56 mL decrease for TTP hypoperfused volume. • Amount of perfusion recovery on TTP map has better performance on the prediction of favorable functional recovery and early neurological improvement than other diffusion- and perfusion-weighted MRI parameters and recanalization grades.

Novel Estimation of Penumbra Zone Based on Infarct Growth Using Machine Learning Techniques in Acute Ischemic Stroke.

While the penumbra zone is traditionally assessed based on perfusion-diffusion mismatch, it can be assessed based on machine learning (ML) prediction of infarct growth. The purpose of this work was to develop and validate an ML method for the prediction of infarct growth distribution and volume, in cases of successful (SR) and unsuccessful recanalization (UR). Pre-treatment perfusion-weighted, diffusion-weighted imaging (DWI) data, and final infarct lesions annotated from day-7 DWI from patients with middle cerebral artery occlusion were utilized to develop and validate two ML models for prediction of tissue fate. SR and UR models were developed from data in patients with modified treatment in cerebral infarction (mTICI) scores of 2b-3 and 0-2a, respectively. When compared to manual infarct annotation, ML-based infarct volume predictions resulted in an intraclass correlation coefficient (ICC) of 0.73 (95% CI = 0.31-0.91, p < 0.01) for UR, and an ICC of 0.87 (95% CI = 0.73-0.94, p < 0.001) for SR. Favorable outcomes for mismatch presence and absence in SR were 50% and 36%, respectively, while they were 61%, 56%, and 25%, respectively, for the low, intermediate, and high infarct growth groups. The presented method can offer novel and alternative insights into selecting patients for recanalization therapy and predicting functional outcome.

Intracranial Aneurysms in Young Adult Patients: Surgical and Endovascular Treatment Outcomes.

BACKGROUND: Despite its relative rarity, the potential for loss of productive years makes aneurysmal subarachnoid hemorrhage (SAH) a considerably important entity in young adult patients (20-39 years of age). This study aimed to analyze outcomes of microsurgery (MS) and endovascular treatment (EVT) for saccular intracranial aneurysms (IAs) in young adult patients. METHODS: A total of 276 young adult patients with 315 IAs, treated with MS or EVT between January 2001 and December 2015, were studied. Major recurrence and treatment-related complications were the primary outcome measures. Functional outcomes in patients with SAH were also assessed. RESULTS: Major recurrence occurred in 21 cases (6.7%). Younger age (adjusted hazard ratio [aHR], 3.77; 95% confidence interval [CI], 1.45-9.83; P = 0.007), ruptured IA (aHR, 6.44; 95% CI, 2.09-19.89; P = 0.001), size (aHR, 1.84; 95% CI, 1.06-3.18; P = 0.030), and EVT (aHR, 7.21; 95% CI, 2.44-21.35; P < 0.001) were independently related to major recurrence. Treatment-related complications occurred in 5 cases (1.6%) and did not differ between the MS and EVT groups (P > 0.999). Unfavorable outcomes (modified Rankin scale score ≥2) were identified in 30 patients (19.6%) with SAH, and only Hunt and Hess grade was independently associated with unfavorable functional outcome. CONCLUSIONS: Both MS and EVT are safe for treating IAs in young adult patients. MS showed better durability of treatment and may be preferred over EVT in young patients in view of their longer life expectancy compared with older patients.

Identification of High Risk Carotid Artery Stenosis: A Multimodal Vascular and Perfusion Imaging Study.

Background: Risk stratification of asymptomatic carotid artery stenosis (ACAS) is still an issue for carotid revascularization. We sought to identify factors associated with symptomatic carotid artery stenosis (SCAS) using multimodal imaging techniques. Methods: We retrospectively collected data on patients who underwent carotid artery revascularization. Results from duplex sonography, computerized tomography angiography, brain magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), perfusion-weighted imaging, and demographic profiles were compared between ACAS and SCAS patients. Differences in baseline characteristics between the two groups were balanced by the propensity matching score method. Multivariable regression analysis was performed to identify factors associated with symptomaticity of carotid artery stenosis. We compared the strength of associations between significant imaging factors and symptomatic carotid stenosis using C statistics. Results: A total of 259 patients (asymptomatic 57.1%, symptomatic 42.9%) with carotid stenosis were included. After 1:1 propensity score matching, the multivariable regression analysis revealed that the absence of plaque calcification [Odds ratio 0.41, 95% confidence interval (CI) 0.182-0.870, p = 0.023], deep white matter hyperintensity (DWMH; Odds ratio 3.46, 95% CI 1.842-6.682, p < 0.001), susceptibility vessel sign seen on gradient-echo MRI (Odds ratio 2.35, 95% CI 1.113-5.107, p = 0.027), and increased cerebral blood volume (CBV) seen on perfusion-weighted MRI (CBV; Odds ratio 2.17, 95% CI 1.075-4.454, p = 0.032) were associated with SCAS. The combination of these variables had a fair accuracy to classify SCAS (Area under the curve 0.733, 95% CI 0.662-0.803). Conclusions: We identified several multimodal imaging markers independently associated with SCAS. These markers may provide information to identify ACAS patients with high risk of ischemic stroke. Future studies are needed to predict SCAS using our findings in other independent cohorts.

Comparison of Clopidogrel and Ticlopidine/Ginkgo Biloba in Patients With Clopidogrel Resistance and Carotid Stenting.

Background and Purpose: Patients undergoing carotid artery stenting (CAS) who show low responsiveness to clopidogrel may have a higher risk of peri-procedural embolic events. This study aimed to compare the effectiveness and safety of clopidogrel and ticlopidine plus Ginkgo biloba in clopidogrel-resistant patients undergoing CAS. Methods: In this multi-center, randomized, controlled trial, we used platelet reactivity test to select patients undergoing CAS who showed clopidogrel resistance, and compared treatments using clopidogrel and ticlopidine plus ginkgo. The primary outcome was the incidence of new ischemic lesion in the ipsilateral hemisphere of CAS. Detection of microembolic signal on transcranial Doppler was the secondary outcome. The clinical outcomes were also monitored. Results: This trial was discontinued after 42 patients were randomized after preplanned interim sample size re-estimation indicated an impractical sample size. The primary endpoint occurred in 12/22 patients (54.5%) in the clopidogrel group and 13/20 patients (65.0%) in the ticlopidine-ginkgo group (P = 0.610). No significant differences in the presence of microembolic signal (15.0 vs. 11.8%, P = 0.580), clinical outcomes (ischemic stroke or transient ischemic attack, 0.0 vs. 5.5%; acute myocardial infarction 0.0 vs. 0.0%; all-cause death, 4.5 vs. 0.0%), or incidence of adverse events were found in the two groups. In terms of resistance to clopidogrel, treatment with ticlopidine-ginkgo significantly increased the P2Y12 Reaction Units (difference, 0.0 [-0.3-3.0] vs. 21.0 [6.0-35.0], P < 0.001). Conclusions: In patients who showed clopidogrel resistance, ticlopidine-ginkgo treatment was safe and increased P2Y12 Reaction Units; however, compared to clopidogrel, it failed to improve surrogate and clinical endpoints in patients undergoing CAS. This multimodal biomarker-based clinical trial is feasible in neurointerventional research. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT02133989.

Cav-1 (Caveolin-1) and Arterial Remodeling in Adult Moyamoya Disease.

Background and Purpose- Moyamoya disease (MMD) is a unique cerebrovascular occlusive disease characterized by progressive stenosis and negative remodeling of the distal internal carotid artery (ICA). We hypothesized that cav-1 (caveolin-1)-a protein that controls the regulation of endothelial vesicular trafficking and signal transduction-is associated with negative remodeling in MMD. Methods- We prospectively recruited 77 consecutive patients with MMD diagnosed via conventional angiography. Seventeen patients with intracranial atherosclerotic stroke and no RNF213 mutation served as controls. The outer distal ICA diameters were examined using high-resolution magnetic resonance imaging. We evaluated whether the degree of negative remodeling in the patients with MMD was associated with RNF213 polymorphism, cav-1 levels, or various clinical and vascular risk factors. We also investigated whether the derived factor was associated with negative remodeling at the cellular level using the tube formation and apoptosis assays. Results- The serum cav-1 level was lower in the patients with MMD than in the controls (0.47±0.29 versus 0.86±0.68 ng/mL; P=0.034). The mean ICA diameter was 2.48±0.98 mm for the 126 affected distal ICAs in patients with MMD and 3.84±0.42 mm for the asymptomatic ICAs in the controls ( P<0.001). After adjusting for confounders, cav-1 levels (coefficient, 1.018; P<0.001) were independently associated with the distal ICA diameter in patients with MMD. In vitro analysis showed that cav-1 downregulation suppressed angiogenesis in the endothelial cells and induced apoptosis in the smooth muscle cells. Conclusions- Our findings suggest that cav-1 may play a major role in negative arterial remodeling in MMD.

Treatment Outcomes with Selective Coil Embolization for Large or Giant Aneurysms : Prognostic Implications of Incomplete Occlusion.

OBJECTIVE: The objectives of this study were to evaluate the immediate and long-term efficacy and safety of coil embolization for large or giant aneurysms. METHODS: One hundred and fifty large or giant aneurysm cases treated with endovascular coil embolization between January 2005 and February 2014 at a single institute were included in this study. Medical records and imaging findings were reviewed. Statistical analysis was performed to evaluate prognostic factors associated with major recurrence (major recanalization or rupture) and delayed thromboembolism after selective coil embolization. RESULTS: Procedure-related symptomatic complications occurred in five (3.3%) patients. The mean clinical and radiological follow-up periods were 38 months (range, 2-110) and 26 months (range, 6-108), respectively. During the follow-up period, the estimated recurrence rate was 4.6% per year. Multivariate analysis using Cox regression showed the degree of occlusion to be the only factor associated with recurrence (p=0.008, hazard ratio 3.15, 95% confidence interval 1.34-7.41). The patient's history of rupture in addition to the size and location of the aneurysm were not associated with recurrence in this study. Delayed infarction occurred in eight cases, and all were incompletely occluded. CONCLUSION: Although immediate postprocedural safety profiles were reasonable, longterm results showed recanalization and thromboembolic events to occur continuously, especially in patients with incomplete occlusion. In addition, incomplete occlusion was associated with delayed thromboembolic complications. Patients with incomplete occlusions should be followed carefully for delayed recurrence or delayed thromboembolic events.