Characteristics and clinical outcomes in atrial fibrillation patients classified using cluster analysis: the Fushimi AF Registry.

AIMS: The risk of adverse events in atrial fibrillation (AF) patients was commonly stratified by risk factors or clinical risk scores. Risk factors often do not occur in isolation and are often found in multimorbidity 'clusters' which may have prognostic implications. We aimed to perform cluster analysis in a cohort of AF patients and to assess the outcomes and prognostic implications of the identified comorbidity cluster phenotypes. METHODS AND RESULTS: The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, Japan. Hierarchical cluster analysis was performed on 4304 patients (mean age: 73.6 years, female; 40.3%, mean CHA2DS2-VASc score 3.37 ± 1.69), using 42 baseline clinical characteristics. On hierarchical cluster analysis, AF patients could be categorized into six statistically driven comorbidity clusters: (i) younger ages (mean age: 48.3 years) with low prevalence of risk factors and comorbidities (n = 209); (ii) elderly (mean age: 74.0 years) with low prevalence of risk factors and comorbidities (n = 1301); (iii) those with high prevalence of atherosclerotic risk factors, but without atherosclerotic disease (n = 1411); (iv) those with atherosclerotic comorbidities (n = 440); (v) those with history of any-cause stroke (n = 681); and (vi) the very elderly (mean age: 83.4 years) (n = 262). Rates of all-cause mortality and major adverse cardiovascular or neurological events can be stratified by these six identified clusters (log-rank test; P < 0.001 and P < 0.001, respectively). CONCLUSIONS: We identified six clinically relevant phenotypes of AF patients on cluster analysis. These phenotypes can be associated with various types of comorbidities and associated with the incidence of clinical outcomes. CLINICAL TRIAL REGISTRATION INFORMATION: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000005834.

History of the European-Japanese Cerebrovascular Congress.

The European-Japanese Cerebrovascular Congress originally started as a Swiss-Japanese joint conference on cerebral aneurysm. The Congress was held in Zürich, Switzerland, from 5-7 May 2001 with Prof. Y. Yonekawa of Zürich and Prof. Y. Sakurai of Sendai as the presidents.Three years later, in July of 2004, the second meeting was held at Zürich again with wide-ranging conference topics on cerebral stroke surgery.The third meeting at Zürich in 2006 was the key congress for future development. The conference was expanded to the European-Japanese Joint Conference for Stroke Surgery.As the year of 2006 was the 70th Anniversary of the Department of Neurosurgery, University Hospital Zürich, Prof. Krayenbühl, Prof. Yasargil, and Prof. Yonekawa introduced the impressive history of the Department of Neurosurgery at the conference.At the fourth European-Japanese Joint Conference on Stroke Surgery we moved from Zürich to the Nordic city of Helsinki, with Prof. Juha Hernesniemi as the conference president.The fifth joint conference was held at Düsseldolf am Rein with Prof. Hans-Jakob Steiger as the Conference president.The sixth conference, named "The European-Japanese Stroke Surgery Conference" (EJSSC), was held in Utrecht, The Netherlands. Professor Luca Regli and Prof. Gabriel Rinkel were the conference presidents.The seventh European-Japanese Stroke Surgery Conference (EJSSC) was held in Verona, Italy with the presidents Prof. Alberto Pasqualin and Prof. Giampietro Pinna.The eighth European-Japanese Cerebrovascular Congress (EJCVC) came back to Zürich in the year 2016 with Prof. Luca Regli as the president.The ninth European-Japanese Cerebrovascular Congress (EJCVC) was held in the historical room of Grande Ospedale Metropolitano Niguarda Milan, Italy, with Prof. Marco Cenzato as the president.The tenth European-Japanese Cerebrovascular Congress (EJCVC) will be held in Kyoto. It will be the first meeting of the EJCVC in Japan.Publication of the proceeding books of the conference as supplements of ACTA Neurochirurgica is one of the main reasons that we have been able to continue this conference for almost 20 years. We sincerely thank Prof. Steiger for his continuous and generous cooperation as the series Editor of ACTA Neurochirurgica.

When Is Diagnostic Subtraction Angiography Indicated Before Clipping of Unruptured and Ruptured Intracranial Aneurysms? An International Survey of Current Practice.

INTRODUCTION: The goal of this survey is to investigate the indications for preoperative digital subtraction angiography (DSA) before clipping of ruptured and unruptured intracranial aneurysms in an international panel of neurovascular specialists. METHODS: An anonymous survey of 23 multiple-choice questions relating to indications for DSA before clipping of an intracranial aneurysm was distributed to the international panel of attendees of the European-Japanese Cerebrovascular Congress (EJCVC), which took place in Milan, Italy on 7-9 June 2018. The survey was collected during the same conference. Descriptive statistics were used to analyze the data. RESULTS: A total of 93 surveys were distributed, and 67 (72%) completed surveys were returned by responders from 13 different countries. Eighty-five percent of all responders were neurosurgeons. For unruptured and ruptured middle cerebral artery (MCA) aneurysms without life-threatening hematoma, approximately 60% of responders perform surgery without preoperative DSA. For aneurysms in other locations than MCA, microsurgery is done without preoperative DSA in 68% of unruptured and in 73% of ruptured cases. In cases of ruptured MCA or ruptured non-MCA aneurysms with life-threatening hematoma, surgery is performed without DSA in 97% and 96% of patients, respectively. Factors which lead to preoperative DSA being performed were: aneurysmal shape (fusiform, dissecting), etiology (infectious), size (>25 mm), possible presence of perforators or efferent vessels arising from the aneurysm, intra-aneurysmal thrombus, previous treatment, location (posterior circulation and paraclinoid aneurysm) and flow-replacement bypass contemplated for final aneurysm treatment. These are all factors that qualify an aneurysm as a complex aneurysm. CONCLUSION: There is still a high variability in the surgeons' preoperative workup regarding the indication for DSA before clipping of ruptured and unruptured intracranial aneurysms, except for ruptured aneurysms with life-threatening hematoma. There is a general consensus among cerebrovascular specialists that any angioanatomical feature indicating a complex aneurysm should lead to a more detailed workup including preoperative DSA.

Pretreatment Blood Pressure is a Simple Predictor of Hemorrhagic Infarction after Intravenous Recombinant Tissue Plasminogen Activator (rt-PA) Therapy.

BACKGROUND: Hemorrhagic infarction (HI) is among the most severe complications that can occur following the administration of intravenous recombinant tissue plasminogen activator (rt-PA). In the present study, we aimed to determine the optimal cut-off points of blood pressure (BP) for HI after rt-PA treatment, and to compare our findings with those for other prediction models. METHODS: We analyzed data from 109 consecutive patients with stroke treated at our hospital between 2009 and 2016. HI was confirmed via computed tomography or magnetic resonance imaging. Patients were classified into a symptomatic HI group, an asymptomatic HI group, and a non-HI group. BP was measured on admission and before rt-PA treatment. Glucose Race Age Sex Pressure Stroke Severity (GRASPS) and Totaled Health Risks in Vascular Events (THRIVE) scores were also calculated. Receiver operating characteristic (ROC) analysis was used to determine factors associated with symptomatic and asymptomatic HI. RESULTS: Among the 109 total patients, 25 patients developed symptomatic HI, while 22 patients developed asymptomatic HI. ROC analysis for predicting symptomatic and asymptomatic HI revealed that the area under the curve for pretreatment systolic BP (SBP) was .88 (95% confidence interval[CI]: .83-.94), while those for GRASPS and THRIVE scores were .75 (95% CI: .66-.85) and .69 (95% CI: .59-.79), respectively. We identified an optimal cut-off point of 160 mm Hg (sensitivity: 82.3%; specificity: 76.6%; diagnostic accuracy: 80.0%; positive predictive value: 76.6%; negative predictive value: 82.5%). CONCLUSIONS: Pre-treatment SBP may be a simple predictor of symptomatic and asymptomatic HI in patients with stroke undergoing rt-PA treatment.

Surgical Treatment of Carotid Artery Stenosis.

BACKGROUND AND PURPOSE: The indications for carotid endarterectomy (CEA) and carotid artery stenting (CAS) have not been established. CEA is more appropriate than CAS if soft atherosclerotic plaques are included in the stenotic lesion, since such soft plaques are associated with a high incidence of ischemic complications during CAS. This report presents our surgical methods and the clinical results of CEA and CAS, and suggests an appropriate treatment strategy using plaque diagnosis, especially for high-risk patients. MATERIALS AND METHODS: From January 2001 until December 2013 we surgically treated carotid stenosis in 241 lesions by CEA, and 309 lesions by CAS. The average age of the patients was 70.5 in CEA and 71.4 in CAS. The symptomatic stenosis rate was 67 % and the average stenotic rate was 82 % in CEA; these were 61 % and 66 %, respectively, in CAS. RESULTS: Stenosis of carotid arteries was relieved in all cases after CEA or CAS. Peri-operative mortality with CEA and CAS was 0.4 % (1/241) and 0.3 % (1/309), respectively. Morbidity by ischemic stroke with CEA and CAS was 2.9 % (7/241) and 1.6 % (5/309), respectively. Surgical morbidity was not high in patients with medical risk factors. CONCLUSIONS: Carotid stenotic lesions can be treated with comparably low morbidity and mortality rates using CEA and/or CAS even with high risks when appropriate surgical methods are selected, considering each characteristic of carotid stenosis using plaque diagnosis.

Association between metabolic syndrome and multiple lesions of intracranial atherothrombotic stroke: a hospital-based study.

BACKGROUND: With the increasing trend of metabolic syndrome (MetS) and atherothrombotic stroke (which can manifest as stroke lesion multiplicity), studies on the association between MetS and the clinical aspects of atherothrombotic stroke are of great interest. The present study aimed to investigate the association between MetS and multiple atherothrombotic strokes in patients with intracranial atherothrombotic stroke. METHODS: A retrospective study based on medical charts was conducted among patients (n = 202: 137 men/65 women) who were symptomatically admitted to the hospital with the first-ever atherothrombotic stroke. For the occurrence of multiple lesions of stroke, odds ratio [OR: 95% confidence interval (CI)] of MetS or its respective components was calculated using logistic regression models. RESULTS: Fifty-one percent of the men and 38% of women with stroke presented multiple regions. MetS was a significant factor that was associated with an increased risk of multiple regions in women [OR 4.3 (95% CI 1.4-13.5)], but not in men. According to the components of MetS, dyslipidemia was a significant factor that was positively associated with multiple regions in both men [OR 2.0 (95% CI 1.1-3.7)] and women [OR 3.2 (95% CI 1.1-9.1)]. CONCLUSION: MetS may be pathophysiologically associated with intracranial atherothrombotic stroke multiplicity in women in particular. Future studies are warranted to confirm the findings.

Follow-up after undersized dilatation of targeted lesions in carotid artery stenting.

BACKGROUND AND PURPOSE: We assessed whether intentional undersized dilatation of targeted lesions during carotid artery stenting (CAS) carried a higher risk of in-stent restenosis (ISR) and correlation to subsequent ischemic stroke in qualifying arteries in the follow-up period. METHODS: Consecutive patients undergoing CAS between April 2003 and May 2010 were retrospectively reviewed. The use of a filter device as a distal embolic protection device (EPD) was first approved by Japanese governmental health insurance in April 2008; previously, transient balloon occlusion was used off-label. Until March 2008 (Group A), the target diameter of balloon dilatation was 80-100% of the normal vessel diameter just distal to the stenotic lesion. Moderately undersized dilatation (70-80% of the normal vessel diameter) using the distal EPD was adopted in April 2008 (Group B) in an attempt to reduce the amount of released plaque debris. RESULTS: We analyzed 132 CAS procedures (125 patients) in Group A and 53 CAS procedures (52 patients) in Group B. The mean follow-up period was 35.4 months (35.3 months in Group A and 36.0 months in Group B). Eight lesions (4.3%; 7 in Group A and 1 in Group B) developed ISR. None of the patients had symptomatic ISR, and ISR did not increase in Group B (odds ratio, 0.34; 95% confidence interval, 0.04-2.86; p = 0.32). CONCLUSIONS: Undersized dilatation of targeted lesions did not increase the risk of developing ISR, and we suggest it as a viable treatment option to prevent ischemic events during CAS.

Endovascular treatment for intracranial vertebrobasilar artery stenosis.

PURPOSE: We describe our experience with endovascular treatment for symptomatic intracranial vertebrobasilar artery stenosis. MATERIALS AND METHODS: Forty-four patients with intracranial vertebrobasilar artery stenosis (37 vertebral arteries, 7 basilar arteries) were treated with endovascular surgery. Indication criteria for the treatment were (1) medically refractory symptomatic patients; (2) angiographic stenosis of more than 60 %; and (3) short lesion (<15 mm). Under local anesthesia, balloon angioplasty was first performed in all patients. Stenting was performed only in cases with insufficient dilatation, dissection, or restenosis after balloon angioplasty. The degree of stenosis, which was 83 % before treatment, was reduced to 23 % after treatment. The rate of stroke and death within 30 days was 2.3 %. Nine patients (20.5 %) developed restenosis within 6 months. Of these, four patients were symptomatic. All symptomatic patients with restenosis were successfully treated with balloon angioplasty or stenting. CONCLUSION: Endovascular treatment for vertebrobasilar artery stenoses is feasible and safe in selected patients. Restenosis may be an important cause of recurrent stroke. Therefore, close clinical and neuroradiological follow-ups are essential for patients treated with endovascular surgery to improve long-term results.

Percutaneous transluminal angioplasty for atherosclerotic stenosis of the subclavian or innominate artery: angiographic and clinical outcomes in 36 patients.

The purpose of the study was to evaluate stenting and percutaneous transluminal angioplasty (PTA) for the treatment of stenotic lesions of the subclavian or innominate artery based on surgical results and long-term follow-up with 36 patients. In particular, we evaluated the efficacy of self-expanding stents compared to balloon-expandable stents. Between February 2000 and March 2008 at the Kyoto Medical Center, 36 patients underwent both stenting and PTA of the subclavian or innominate artery. Twenty-four patients had severe subclavian stenotic disease, ten patients had total occlusion of the subclavian artery, and two patients had stenoses of the innominate artery. Successful dilatation (less than 30% residual stenosis) was obtained in 34 of the 36 cases. In two cases (20%) of total subclavian occlusion, the guidewires were not able to penetrate the lesions, although the success rate was 100% for stenoses. All patients had no signs of neurological side effects with the exception of two pseudoaneurysms of the femoral arteries that required surgical intervention. In the first 30 days after treatment, there were no strokes or deaths. Outpatient follow-up was done with 30 patients (83.3%) after a mean of 30.9 months (range 3-114). Among these 30 patients, four patients (13.3%) developed restenoses of over 50%. Restenoses occurred in 4 of 20 individuals (20%) who received balloon-expandable stents but were not observed in those who received self-expanding stents. Endovascular therapy for the subclavian and innominate arteries is less invasive and safer than open surgery, making it the preferable option. In this clinical period, the rate of restenosis using self-expanding stents was lower than the rate using balloon-expandable stents.

Predicting cerebral infarction in patients with atrial fibrillation using machine learning: The Fushimi AF registry.

The CHADS2 and CHA2DS2-VASc scores are widely used to assess ischemic risk in the patients with atrial fibrillation (AF). However, the discrimination performance of these scores is limited. Using the data from a community-based prospective cohort study, we sought to construct a machine learning-based prediction model for cerebral infarction in patients with AF, and to compare its performance with the existing scores. All consecutive patients with AF treated at 81 study institutions from March 2011 to May 2017 were enrolled (n = 4396). The whole dataset was divided into a derivation cohort (n = 1005) and validation cohort (n = 752) after excluding the patients with valvular AF and anticoagulation therapy. Using the derivation cohort dataset, a machine learning model based on gradient boosting tree algorithm (ML) was built to predict cerebral infarction. In the validation cohort, the receiver operating characteristic area under the curve of the ML model was higher than those of the existing models according to the Hanley and McNeil method: ML, 0.72 (95%CI, 0.66-0.79); CHADS2, 0.61 (95%CI, 0.53-0.69); CHA2DS2-VASc, 0.62 (95%CI, 0.54-0.70). As a conclusion, machine learning algorithm have the potential to perform better than the CHADS2 and CHA2DS2-VASc scores for predicting cerebral infarction in patients with non-valvular AF.

Hemodynamic Risk Factors for the Development of Carotid Stenosis in Patients with Unilateral Carotid Stenosis.

BACKGROUND: It is difficult to predict the development of carotid stenosis by means of the known risk factors. Using a computational fluid dynamics analysis, we examined the hemodynamic risks for carotid stenosis, focusing on wall shear stress (WSS) disturbances. METHODS: In 59 patients with unilateral carotid stenosis, the plaque was removed from the original three-dimensional computed tomography angiographic images, and the vessel shape before stenosis was artificially reproduced. A multivariate regression analysis was performed to determine the associations between the degree of area stenosis and hemodynamic and morphologic factors after adjustment for 6 known risk factors. RESULTS: Metrics for WSS disturbances were higher at and distal to a bifurcation in the carotid arteries after plaque removal compared with the normal carotid arteries, and metrics for WSS magnitudes were lower. In the plaque-removed arteries, the degree of stenosis was significantly negatively correlated with the ratio of stenotic to distal values of metrics for WSS disturbances and the diameter ratio of the external to common carotid artery, and positively correlated with the ratio of proximal to stenotic values of metrics for WSS magnitudes. CONCLUSIONS: Rapid increases in WSS from the common carotid artery toward the bifurcation, rapid decreases in WSS disturbance from the bifurcation toward the internal carotid artery, and lower diameter ratio of the external to common carotid artery are more likely than other risk factors to cause future severe stenosis. In patients with these hemodynamic risks, underlying diseases should be controlled more strictly, with imaging examinations at shorter intervals.

Characteristics of carotid plaque findings on ultrasonography and black blood magnetic resonance imaging in comparison with pathological findings.

BACKGROUND: Criteria to decide whether carotid endarterectomy (CEA) or carotid artery stenting (CAS) is the best mode of therapy in a specific case of cervical carotid stenosis have not been established. Overall, recent randomized clinical trials have reported that the effect on the prevention of stroke is not significantly different between CEA and CAS. CEA is more appropriate than CAS for soft atherosclerotic plaques, since such soft plaques are associated with a high incidence of ischemic complications during CAS. Therefore identification of the plaque type with noninvasive preoperative examinations plays an important role for selecting the suitable surgical method, CEA or CAS. OBJECTIVE: The objective of this study was to evaluate the association among findings of carotid ultrasonography (carotid US), black blood magnetic resonance imaging (BB-MRI), and the histopathological findings of plaque specimens removed during CEA, and secondly to consider whether these diagnostic tools are useful to predict the characteristics of carotid plaques. METHOD: We investigated a total of 25 consecutive patients who underwent CEA from November 2008 to June 2010 at Kyoto Medical Center. We examined carotid plaque in 17 patients employing both carotid US and BB-MRI, 7 patients by carotid US, and 1 patient by BB-MRI. The plaque echogenicity was qualitatively assessed as low, intermediate, or high, and the MR signal intensity of the carotid plaque was classified as low or high compared with the intensity of the ipsilateral sternocleidomastoid muscle. The plaque specimens were macroscopically and pathophysiologically classified as soft or hard plaque. RESULTS: All low-echogenic plaques on carotid US were histologically soft plaques. The high-intensity plaques on T1-weighted imaging (T1WI) showed a tendency toward soft plaque. Thirteen of 14 plaques with high signal intensity on T1WI were morphologically soft. Eleven of 14 plaques with an intermediate echogenicity on carotid US were also morphologically soft. CONCLUSION: The findings of carotid ultrasonography and BB-MRI are closely associated with the CEA specimen's morphology. Ultrasonography alone is insufficient to diagnose the plaque type accurately in some patients. Employing both carotid US and BB-MRI is useful for evaluating the characteristics of carotid plaque.

Indication for surgical treatment of carotid arterial stenosis in high-risk patients.

The indication for carotid endarterectomy (CEA) or carotid artery stenting (CAS) has not been established, although the beneficial effects of these surgical treatments for severe cervical carotid stenosis have been confirmed by clinical trial studies. We report our clinical results of CAS and CEA and suggest an appropriate treatment strategy, especially for high-risk patients. From January 2001 to December 2009, we treated 171 carotid lesions by CEA and 251 lesions by CAS. Stenosis was symptomatic in 68%, and the average stenotic rate was 83% in the CEA group. In the CAS group, stenosis was symptomatic in 62%, and the average stenotic rate was 65%. Stenosis was relieved in all cases after CEA or CAS. Surgical mortality with CEA and CAS was 0.6% (1/171) and 0.4% (1/251), respectively. Surgical morbidity by ischemic stroke with CEA and CAS was 2.9% (5/171) and 1.2% (3/251), respectively. Surgical morbidity was not increased in patients with medical risk factors. The long-term outcome after CAS was not inferior to that after CEA. In conclusion, carotid stenosis can be treated with comparably low morbidity and mortality rates using CEA or CAS even in high-risk patients when the method is appropriately selected considering the characteristics of the carotid stenosis.

Overview of spontaneous cervicocephalic arterial dissection in Japan.

Spontaneous cervicocephalic arterial dissection (SCAD) has been recognized as an uncommon cause of cerebral stroke. Although it has been viewed as an important cause of stroke, especially in juvenile cases, its natural course and pathophysiology have yet to be fully clarified, and no treatment criteria have been established. Recent studies have suggested that clinical features of SCAD in Japan are different from those in European countries. Herein, we reviewed the current status of the management of SCAD in Japan, and clarified its clinical characteristics to establish an appropriate treatment.

Long-term results of carotid endarterectomy and carotid stenting.

INTRODUCTION: We report the long-term results of surgery for carotid stenosis in our institute, and suggest a better treatment strategy for high-risk patients. MATERIALS AND METHODS: Our series of 352 carotid surgeries conducted between April 1998 and May 2007 were investigated. CEA comprised 134 (38%), whereas CAS comprised 218 (62%). In August 2007, we sent questionnaires to all patients, and analyzed responses up to May 2008. For patients undergoing regular follow-up, the data were gathered from the medical records. The questions were: (1) mRS at that time, (2) the cause of death if the patient was deceased, (3) newly diagnosed stroke, and (4) newly diagnosed coronary heart disease. RESULTS: The response rate was 68.8%. The average follow-up period was 31.2 months. The average differences in mRS pre- and postoperation were -0.33 and -0.48 in CEA and CAS, respectively. The mortality rate at >30days was 8.2% in CEA, and 5.0% in CAS. The leading cause of death was heart disease (31.8%). CONCLUSION: Our report suggests that CAS is not inferior to CEA, and both procedures can be managed safely if all characteristics of the carotid lesions are considered.

Endovascular treatment of acute ischaemic stroke in octogenarians and nonagenarians compared with younger patients.

Purpose: Endovascular therapy for emergent large vessel occlusion has been established as the standard approach for acute ischaemic stroke. However, the effectiveness and safety of endovascular therapy in the very elderly population has not been proved. Objective: To determine the safety and effectiveness of endovascular therapy in octogenarians and nonagenarians. Methods: We retrospectively reviewed all patients who underwent endovascular therapy at two stroke centres between April 2012 and July 2018. Functional outcome was assessed using the modified Rankin scale at 90 days after stroke or at discharge. A favourable outcome was defined as a modified Rankin scale score of 0-2 or not worsening of the modified Rankin scale score before stroke. Outcome was compared between younger patients (aged 46-79 years, n = 40) and octogenarians and nonagenarians (aged 80-97 years, n = 19). Results: Octogenarian and nonagenarian patients had pre-stroke functional deficit (modified Rankin scale score >1) more frequently than younger patients (57.9% vs. 20.0%, respectively, P = 0.0059). No difference was observed between very elderly and younger patients in the rate of successful reperfusion (89.5% vs. 67.5%, respectively, P = 0.11), favourable functional outcome (47.4% vs. 45.0%, respectively, P = 1.00) and mortality (21.1% vs. 27.5%, respectively, P = 1.00). On multiple regression analysis, successful reperfusion, concomitant use of intravenous thrombolysis, and out-of-hospital onset were independent predictors of favourable outcome (P = 0.0003, 0.015 and 0.028, respectively). Conclusions: Successful reperfusion, concomitant use of intravenous thrombolysis, and out-of-hospital onset were clinical predictors of favourable outcome. However, we did not observe an age-dependent effect of clinical outcome after endovascular therapy.

Postoperative ischemic events in patients undergoing carotid artery stenting using algorithmic selection for embolic protection.

PURPOSE: Carotid artery stenting (CAS) is a valuable alternative to carotid endarterectomy, especially in high-risk patients. However, the reported incidences of perioperative stroke and death remain higher than for carotid endarterectomy, even when using embolic protection devices (EPDs) during CAS. Our purpose was to evaluate 30-day major adverse events after CAS when selecting the most appropriate EPD. METHODS: We reviewed the clinical outcomes of 61 patients with 64 lesions who underwent CAS with EPDs. Patients who underwent CAS associated with thrombectomy and who had a preoperative modified Rankin scale score >3 were excluded from the analysis. The EPD was selected based on symptoms, carotid wall magnetic resonance imaging and lesion length, and we analyzed combined 30-day complication rates (transient ischemic attack, minor stroke, major stroke or death). RESULTS: Forty-nine patients were men and 12 were women. The median age was 72 years (range: 59-89 years) and 44 lesions were asymptomatic. A filter-type EPD was selected in 23 procedures, distal-balloon protection in 14 procedures and proximal-occlusive protection in 27 procedures. Two patients (3.1%) experienced a transient ischemic attack and one patient (1.6%) had a minor stroke within 30 days of the procedure. No patients experienced procedure-related morbidities (modified Rankin score >2) or death. CONCLUSIONS: The perioperative stoke rate was low when we selected a proximal-occlusive-type EPD in high-risk patients with vulnerable carotid artery disease. Our algorithm for EPD selection was an effective tool in the perioperative management of carotid artery stenosis.

Disruption of P2X4 purinoceptor and suppression of the inflammation associated with cerebral aneurysm formation.

OBJECTIVE: There are no effective therapeutic drugs for cerebral aneurysms, partly because the pathogenesis remains unresolved. Chronic inflammation of the cerebral arterial wall plays an important role in aneurysm formation, but it is not clear what triggers the inflammation. The authors have observed that vascular endothelial P2X4 purinoceptor is involved in flow-sensitive mechanisms that regulate vascular remodeling. They have thus hypothesized that shear stress-associated hemodynamic stress on the endothelium causes the inflammatory process in the cerebral aneurysm development. METHODS: To test their hypothesis, the authors examined the role of P2X4 in cerebral aneurysm development by using P2X4-/- mice and rats that were treated with a P2X4 inhibitor, paroxetine, and subjected to aneurysm-inducing surgery. Cerebral aneurysms were induced by unilateral carotid artery ligation and renovascular hypertension. RESULTS: The frequency of aneurysm induction evaluated by light microscopy was significantly lower in the P2X4-/- mice (p = 0.0488) and in the paroxetine-treated male (p = 0.0253) and female (p = 0.0204) rats compared to control mice and rats, respectively. In addition, application of paroxetine from 2 weeks after surgery led to a significant reduction in aneurysm size in the rats euthanized 3 weeks after aneurysm-inducing surgery (p = 0.0145), indicating that paroxetine suppressed enlargement of formed aneurysms. The mRNA and protein expression levels of known inflammatory contributors to aneurysm formation (monocyte chemoattractant protein-1 [MCP-1], interleukin-1ß [IL-1ß], tumor necrosis factor-α [TNFα], inducible nitric oxide synthase [iNOS], and cyclooxygenase-2 [COX-2]) were all significantly elevated in the rats that underwent the aneurysm-inducing surgery compared to the nonsurgical group, and the values in the surgical group were all significantly decreased by paroxetine administration according to quantitative polymerase chain reaction techniques and Western blotting. Although immunolabeling densities for COX-2, iNOS, and MCP-1 were not readily observed in the nonsurgical mouse groups, such densities were clearly seen in the arterial wall of P2X4+/+ mice after aneurysm-inducing surgery. In contrast, in the P2X4-/- mice after the surgery, immunolabeling of COX-2 and iNOS was not observed in the arterial wall, whereas that of MCP-1 was readily observed in the adventitia, but not the intima. CONCLUSIONS: These data suggest that P2X4 is required for the inflammation that contributes to both cerebral aneurysm formation and growth. Enhanced shear stress-associated hemodynamic stress on the vascular endothelium may trigger cerebral aneurysm development. Paroxetine may have potential for the clinical treatment of cerebral aneurysms, given that this agent exhibits efficacy as a clinical antidepressant.

Pazopanib-mediated Long-term Disease Stabilization after Local Recurrence and Distant Metastasis of Primary Intracranial Leiomyosarcoma: A Case Report on the Efficacy of Pazopanib as a Salvage Therapy.

Primary intracranial leiomyosarcoma (LMS) is an extremely rare tumor of the central nervous system. Only sporadic case reports have been published, and therefore data regarding long-term prognosis remain scarce. A 76-year-old woman presented with a right parietal mass, which had grown rapidly in the month prior to admission. Neuroimaging showed a resemblance to intraosseous meningioma. Gross total resection of the tumor was achieved, and histological diagnosis confirmed LMS. Because positron emission tomography (PET) with fluorodeoxyglucose (FDG) just after the resection showed no abnormal uptake, we diagnosed the tumor as primary intracranial LMS. Follow-up PET at 16 months after treatment showed two foci of FDG uptake in the bilateral lungs. Histological diagnosis by surgical resection identified the lesions as lung metastases of LMS. In addition, follow-up head magnetic resonance imaging (MRI) at 31 months showed local recurrence, and we conducted salvage therapy using CyberKnife system (Accuray incorporated) and pazopanib. To date, for 15 months after local recurrence, she is alive with intracranial recurrent disease remained inactive.

Predictors of Cardioembolic Stroke in Japanese Patients with Atrial Fibrillation in the Fushimi AF Registry.

BACKGROUND: Large-scale clinical trials have analyzed risk factors for any ischemic stroke in patients with atrial fibrillation (AF). However, the risk factors for cardioembolic stroke (CES), specifically, have not been reported. To clarify the risk factors for CES and clinically significant cardioembolic infarction, we examined the incidence of CES and larger infarct volume (IV) (> 30 mL) CES, employing the Fushimi AF Registry, a community-based prospective cohort of AF patients in the Fushimi ward, Kyoto, Japan. METHODS: A total of 4,182 Fushimi AF patients were enrolled from March 2011 to December 2014. The risk factors for CES were evaluated using multivariate analysis. RESULTS: Of 4,182 patients enrolled, 3,749 patients were observed for ≥1 year. During the follow-up period (mean duration, 979 ± 7.7 days), 91/3,749 patients experienced a CES (2.43%). Significant risk factors associated with CES were older age (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.01-1.72; p = 0.046), low body weight (OR, 1.30; 95% CI, 1.03-1.65; p = 0.033), sustained AF (OR, 1.67; 95% CI, 1.05-2.71; p = 0.034), and previous stroke or transient ischemic attack (TIA) (OR, 1.94; 95% CI, 1.22-3.06; p = 0.004). Predictors of a large IV were chronic kidney disease (CKD) (OR, 2.08; 95% CI, 1.09-4.05; p = 0.027) and previous stroke/TIA (OR, 2.27; 95% CI, 1.19-4.24; p = 0.011). CONCLUSIONS: In this population-based cohort of Japanese patients with AF, in addition to previous stroke/TIA and older age, sustained AF and low body weight emerged as risk factors for CES, as opposed to any stroke, which may have a different risk profile. Patients with CKD or previous stroke/TIA who developed cardioembolic infarction exhibited more advanced severity. There is a need for direct oral anticoagulants that can be used safely in patients with comorbid AF and CKD.