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Objective: Intracerebral hematoma involves two mechanisms leading to brain injury: the mechanical disruption of adjacent brain tissue by the hematoma and delayed neurological injury. Delayed neurological injury involves perihematomal edema (PHE) formation. Infectious complications following intracerebral hemorrhage (ICH) are a significant contributor to post-ICH recovery. We sought to identify a correlation between PHE volumes and infectious complications following ICH. We also sought to explore the clinical impact of this association., Materials and Methods: This retrospective study included 143 patients with spontaneous ICH. CT scans were performed on admission, and 3 h, 24 h, and 72 h following admission. Hematoma and PHE volumes were calculated using a semi-automatic method. The absolute PHE volume at each time point and changes in PHE volume (ΔPHE) were calculated. Neutrophil to lymphocyte ratio (NLR) and serum C-reactive protein (CRP) levels were measured from the obtained blood samples. Neurological deterioration (ND) was assessed in all patients., Results: Infectious complications were associated with ΔPHE 72-24 (P < 0.01), whereas there was no association between infectious complications and ΔPHE 24-3 (P = 0.09) or ΔPHE 3-ad (P = 0.81). There was a positive correlation between ΔPHE 72-24 and NLR (r = 0.85, 95% CI: 0.79-0.90, P < 0.01) and between ΔPHE 72-24 and CRP levels (r = 0.89, 95% CI: 0.84-0.92, P < 0.01). The ND rate in the group of patients with infectious complications comorbid with high ΔPHE 72-24 was higher than the other patient groups (P < 0.01)., Conclusions: This study revealed a correlation between ΔPHE 72-24 and infectious complications after spontaneous ICH, which was associated with markers of systemic inflammation. This phenotype linkage is a negative cascade that drives ND., Competing Interests: Declaration of Competing Interest This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Object: Abnormal collateral channels, so-called moyamoya vessels, play a critical role to compensate cerebral ischemia, but carry the risk for hemorrhagic stroke in moyamoya disease (MMD). The present study was aimed to clarify if superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and encephalo-myo-duro-arterio-pericranial synangiosis (EDMAPS) can efficiently regress the abnormal collateral channels in MMD patients., Methods: This study included 92 hemispheres of 61 MMD patients who underwent STA-MCA anastomosis combined with EDMAPS between 2013 and 2019. There were 17 children and 44 adults. We retrospectively analyzed the findings on cerebral angiography before and 3 to 6 months after surgery, including Suzuki's angiographical stage, the development of surgical collaterals, and the extent of abnormal collateral channels such as lenticulostriate, thalamic, and choroidal channels., Results: Following surgery, no pediatric and adult patients experienced any stroke during follow-up periods (40.2±25.5 and 54.9±19.7 months, respectively). Suzuki's stage significantly advanced in both adult and pediatric patients after surgery (P=0.042 and P<0.001). In adult patients, all of the lenticulostriate, thalamic, and choroidal channels significantly regressed after surgery (P<0.001, P=0.012, and P=0.004, respectively). In pediatric patients, however, lenticulostriate and choroidal channels significantly regressed (P=0.005 and P=0.034, respectively). Correlation analysis revealed that the development of surgical collaterals determined the postoperative regression of choroidal channels (P<0.001)., Conclusion: STA-MCA anastomosis and EDMAPS may be one of the most effective procedures to widely provide surgical collaterals to the operated hemispheres and prevent not only ischemic but also hemorrhagic stroke by regressing the hemorrhage-prone abnormal collateral channels in MMD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Chronic systemic inflammation is prevalent in patients with chronic kidney disease (CKD) and is linked to the development of cerebrovascular disease. In this study, we explored the association between the unstable plaques and preoperative CKD in patients who underwent carotid endarterectomy (CEA)/carotid artery stenting (CAS). Furthermore, this study also aimed to explore whether there is a difference in the aggravation of renal function with the presence of stable or unstable plaques., Patients and Methods: The study included 90 patients who underwent CEA/CAS for carotid artery stenosis. Multivariate analysis was performed to determine the risk factors for CKD. Kaplan-Meier estimation was employed to evaluate the aggravation of renal function following CEA/CAS., Results: Multivariate analysis revealed that contralateral carotid occlusive disease (odds ratio [OR], 4.45; 95% confidence interval [CI], 1.36-14.6), and T1 high-intensity carotid plaque (OR, 3.26; 95% CI, 1.2-8.86) were independent factors of CKD. Kaplan-Meier estimation demonstrated a higher aggravation of renal function in the T1 high-intensity group compared to those in the iso-intensity (P =.03). Following CEA/CAS, the time until aggravation of renal insufficiency was 12.0 ± 9.4 months in the T1 high-intensity group and 24.5 ± 9.6 months in the iso-intensity group (P =.03)., Conclusions: This study demonstrated that contralateral carotid artery stenosis and T1 high-intensity plaques are more frequently observed in patients with CKD. T1 high-intensity carotid plaque is well linked to CKD development in future., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: There are a variety of collateral routes to compensate persistent cerebral ischemia in moyamoya disease. However, there is no report presenting the persistent primitive olfactory artery (POA) as a spontaneous collateral route to the anterior cerebral artery (ACA) in moyamoya disease., Methods: We precisely examined cerebral angiography in 84 patients with moyamoya disease to identify the collateral channel through the persistent POA. Its anatomy was evaluated on pre- and postoperative angiography., Results: Of 84 patients, four (4.8%) had spontaneous collateral channel through the persistent POA. All of these four hemispheres were categorized into Stage 5. In all four patients, the collateral blood flow arose from the ophthalmic artery and run to the persistent POA through the ethmoidal moyamoya. The persistent POA provided collateral blood flow from the ophthalmic artery to the ACA in all four patients. Superficial temporal artery to middle cerebral artery anastomosis and encephalo-duro-myo-arterio-pericranial synangiosis was performed in three of four patients. After surgery, the collateral channel through the persistent POA completely disappeared or markedly regressed, suggesting a significant improvement of cerebral hemodynamics in the territory of not only the MCA but also the ACA., Conclusion: The persistent POA can potentially provide collateral blood flow to the ACA in about 5% of patients with moyamoya disease, and should be recognized as a novel collateral channel in moyamoya disease. The persistent POA may be useful to evaluate therapeutic effects of surgical revascularization on the ACA territory., (Copyright © 2018. Published by Elsevier Inc.)

Object: Recent clinical studies have recently demonstrated a strong association between carotid artery stenosis and coronary artery disease (CAD). However, the clinical impact of carotid plaque composition on CAD remains unclear. This study was aimed to determine the relationship between carotid plaque composition and CAD in patients who underwent carotid endarterectomy (CEA) or carotid artery stenting (CAS)., Methods: This prospective cohort study included a total of 97 patients who were admitted to our institution between January 2012 and April 2016. Magnetic resonance (MR) imaging was performed to semi-quantitatively analyze the components of carotid plaques by calculating the ratio of plaque intensity to muscle intensity on T1-weighted image. Diagnosis of CAD was based on patient history and clinical examinations during preoperative, postoperative and follow-up periods. Multivariate logistic analysis was performed to determine the risk factors for CAD. The relationship between contralateral plaque composition and CAD was also investigated., Results: Of 97 patients, 33 were diagnosed as having 44 episodes of CAD. Multivariate logistic analysis revealed that ASO (odds ratio [OR], 5.7; 95% confidence interval [CI], 1.8-18.9), contralateral carotid occlusive disease (OR, 6.5; 95%CI, 1.7-22.9), and plaque/muscle ratio (OR, 3.0; 95%CI, 1.4-10.1) were independent factors for predicting CAD. The patients diagnosed as having CAD during the follow-up period had significantly higher plaque/muscle ratio than those with CAD on preoperative evaluations (2.29 ± .21vs. 1.97 ± .33, P < .01)., Conclusions: This study clearly demonstrates that ASO, contralateral carotid artery stenosis, and high-intensity carotid plaque on T1-weighted MRI independently predict CAD. Contralateral carotid plaque composition was also associated with concomitant CAD. Moreover, high-intensity carotid plaque may predict the future development of CAD. Therefore, unstable carotid plaque should be considered as the clinical phenotype of systemic inflammation and a novel, robust marker for future CAD., (Copyright © 2018. Published by Elsevier Inc.)

Background and Purpose: This study was aimed to assess the hypothesis that unstable plaque formation in the carotid artery is one of phenotypes of chronic and systemic inflammation., Methods: This study included 8 symptomatic patients with internal carotid stenosis (ICS) and 7 healthy controls. All subjects underwent 18 F-fluorodeoxyglucos positron emission tomography ( 18 F-FDG PET) of whole body. Plaque vulnerability was evaluated on magnetic resonance imaging (MRI). On 18 F-FDG PET, the maximum standardized uptake (SUVmax) value was measured in the carotid plaque, aorta, spleen, liver, and bone marrow. The SUVmax ratio of the spleen or bone marrow to the liver was also calculated. These values were compared between 2 groups. All 8 patients in ICS group underwent carotid endarterectomy, and surgical specimens were subjected to immunohistochemistry., Results: All 8 patients in ICS group had unstable plaque on MRI. The mean SUVmax of carotid plaque was 2.5 ± .2 in ICS group. The SUVmax of spleen was significantly higher in ICS group than in the controls (3.20 ±  .25 and 2.51 ±  .40, respectively; P = .003). The SUVmax ratio (spleen/liver) was also significantly higher in ICS group than in the controls (1.12 ±  .06 and .85 ±  .12, respectively; P = .001). The SUVmax of aorta was also significantly higher in ICS group than in the controls (2.16 ±  .27 and 1.48 ±  .15, respectively; P = .001). However, there were no significant differences in the SUVmax in the bone marrow and SUVmax ratio (bone marrow/liver) between the 2 groups (P = .811 and P = .731, respectively). Histological examination showed that the plaque strongly expressed endothelial progenitor cells, microvessels, and M1 macrophages., Conclusions: These data strongly suggest the inflammation coupling between the spleen and unstable carotid plaque, and may be useful to develop novel therapeutic strategies against systemic inflammation in patients with ICS., (Copyright © 2018. Published by Elsevier Inc.)

Background: Although the natural course of extracranial carotid artery aneurysms (ECAAs) is still unknown, they may cause stroke or cranial nerve dysfunction unless they are treated. In this report, we reviewed the clinical results of 6 patients who underwent endovascular and surgical treatments for ECAAs., Methods: A total of 6 patients underwent endovascular and surgical treatments for ECAAs for 9 years. The primary causes of ECAAs included Marfan syndrome (1 patient), infection (1 patient), trauma (2 patients), and unknown (2 patients). All 6 ECAAs were symptomatic., Results: One patient underwent surgical resection of the ECAA followed by end-to-end anastomosis of the internal carotid artery (ICA). Another patient underwent proximal ICA ligation combined with high-flow external carotid artery-to-middle cerebral artery bypass using a radial artery graft, because the patient also had a giant thrombosed aneurysm in the cavernous portion of the ipsilateral ICA. Endovascular treatment was selected in the other 4 patients using a covered stent or a bare metal stent combined with coil embolization. Of these patients, one required proximal ICA ligation followed by superficial temporal artery-to-middle cerebral artery anastomosis due to an anatomical problem for stent placement. There was no neurological deterioration at the discharge in all but 1 patient who suffered ischemic stroke during surgery., Conclusion: Surgical or endovascular treatment yielded a relatively satisfactory outcome in patients with ECAAs., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The authors describe herein the first adult case with moyamoya disease associated with protein Z deficiency. A 41-year-old woman was admitted to our hospital due to sudden onset of dysarthria and left extremity weakness 6 days after the delivery of her first baby. Previously, she repeated early fetal losses and was diagnosed with protein Z deficiency. Laboratory examination showed that the plasma concentration of protein Z was .73 µg/ml, being lower than the control. Radiological examination demonstrated typical findings of moyamoya disease with advanced stage on both sides. She successfully underwent surgical revascularization on both sides and was free from any cerebrovascular events during a follow-up period of 2 years. In addition to hemodynamic compromise, protein Z deficiency and hypercoagulation state after delivery might cause ischemic stroke in this case., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Quasi-moyamoya disease (MMD) or moyamoya syndrome is based on various underlying diseases and radiologically simulates MMD, but its disease entity is still unclear. Recent studies have proven specific shrinkage of the involved arteries in MMD. Using 3-dimensional constructive interference in steady state (3D-CISS), therefore, this study aimed to analyze the outer diameter of the involved arteries in quasi-MMD., Methods: This study included 9 patients with quasi-MMD (unilateral type, n = 2; bilateral type, n = 7). Using 3D-CISS, the outer diameter was quantified in the internal carotid artery distal to the posterior communicating artery (C1), the horizontal portion of the middle and anterior cerebral arteries (M1 and A1, respectively), and the basilar artery. Control values were obtained from 17 healthy subjects., Results: In 7 of 9 patients, the outer diameters of C1, M1, and A1 were significantly smaller than those of the controls. On the other hand, the values were normal in other 2 patients. There was no significant difference in the underlying disorders between the 2 groups. All 3 pediatric patients are categorized into the arterial shrinkage group, but 2 of 6 adult patients were not., Conclusions: These findings strongly suggest that quasi-MMD is not a uniform disease entity and includes at least 2 pathophysiologically different groups: the arterial shrinkage group and the nonarterial shrinkage group. A certain subgroup of MMD patients may be misdiagnosed as quasi-MMD because of the patients' comorbid disorders and mixed up with the patients who present angiographic findings similar to MMD in spite of the lack of arterial shrinkage., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Previously, we reported on the differentiation between patients with Alzheimer disease and normal controls using a quantitative electroencephalographic technique called neuronal activity topography (NAT). In this technique, cerebral neuronal activities are characterized by the signal intensity and coherence (sNAT and vNAT, respectively). In the present study, we examined 47 patients with vascular cognitive impairment in carotid stenosis and 52 normal controls. All subjects underwent electroencephalography in a resting state with closed eyes for 5 minutes. Electroencephalographic markers of the differential likelihood, that is, the sensitivity-versus-specificity characteristics, sL(x:VCI-NLc) and vL(x:VCI-NLc), were assessed with neuronal activity topography and were compared between the 2 groups. sL(x:VCI-NLc) and vL(x:VCI-NLc) crossed each other at a cutoff value of the differential likelihood. Separation of the patients and controls was made with a sensitivity of 92% and 88%, as well as a false-positive rate of 8% and 12% for sL(x:VCI-NLc) and vL(x:VCI-NLc), respectively. Using sNAT, we accurately differentiated 92% patients with vascular cognitive impairment. We recommend that sNAT, rather than vNAT, should be used in detecting vascular cognitive impaired patients., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Antiplatelet agents have an important role in the prevention of ischemic complications during endovascular treatment. The aim of this study was to identify correlations between the clinical outcomes of neurointervention. This study also aimed to determine the optimal cutoff for P2Y12 percent inhibition to prevent ischemic and bleeding complications and to confirm the accuracy of the cutoff value., Methods: A prospective study was conducted for all patients (n = 66) who received antiplatelet therapy during neurointervention at Toyama University Hospital during a 25-month period. Platelet reactivity was measured before the procedure using the VerifyNow and filter pressure methods. The primary outcome was the 30-day incidence of adverse clinical events, defined as ischemic or bleeding events, in relation to P2Y12 percent inhibition distribution., Results: Multivariate analysis showed that P2Y12 percent inhibition was an independent predictor for bleeding (P = .021, odds ratio [OR] = 3.45; 95% confidence interval [CI], 2.31-4.88) and ischemic (P = .045, OR = 3.63; 95% CI, 2.11-7.12) events. In receiver operating characteristic curve analysis, P2Y12 percent inhibition could significantly discriminate between patients with and without bleeding and ischemic events. The optimal cutoffs for bleeding (74%) and ischemic events (26%) were used to define 3 groups: those with poor response, sufficient response, and hyper-response. Ischemic and bleeding complications were significantly different among the 3 groups., Conclusions: Optimal threshold, measured using the VerifyNow P2Y12 assay, can be identified using specific thresholds (26% < percent inhibition < 74%) to define patients at lower risk for ischemic and bleeding events. The threshold for hyper-response can highly predict bleeding events in perioperative period. On the other hands, cutoff value for poor response may be affected by various factors., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to evaluate the efficacy of endovascular treatment (EVT) in elderly patients (≥ 75 years of age) with acute large-vessel occlusion (LVO)., Methods: A total of 229 patients with acute LVO treated by EVT in 2008 were registered from 68 medical centers in Japan. Among the total of 229 patients, 89 were elderly patients. We retrospectively investigated the treatment efficacy of EVT and patient outcome, and compared the parameters between the elderly and the nonelderly group., Results: Recanalization after EVT was equally obtained in both groups (P = .71). There was no significant difference in the favorable outcome (modified Rankin Scale [mRS] 0-2) between the elderly and nonelderly groups (30.3% vs 33.6%; P = .61), whereas poor outcome (mRS 5 and 6) was observed more in the elderly group than in the nonelderly group (48.3% vs 32.1%; P = .01). In patients with any recanalization (Thrombolysis in Myocardial Infarction grading system 1-3), the rates of favorable outcome in both groups were similar (39.7% vs 42.6%; P = .71). In contrast, in patients without recanalization, there was a significant difference in the poor outcome between the elderly and the nonelderly groups (76.2% vs 46.7%; P = .046). Symptomatic intracranial hemorrhage occurred in 6.7% in the elderly group and in 11.4% in the nonelderly group (P = .23)., Conclusions: The elderly population could achieve favorable outcomes comparable to the nonelderly population, especially when they achieve any recanalization by EVT. Elderly patients should not be excluded from recanalization therapy with EVT because of age., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Restenosis after carotid artery stenting (CAS) is a critical issue. Cilostazol can reduce restenosis after interventions in coronary or femoropopliteal arteries. We investigated whether periprocedural cilostazol treatment was related to the incidence of in-stent restenosis (ISR) or target vessel revascularization (TVR) after CAS. The study group comprised 553 of 580 patients who underwent CAS between April 2003 and August 2006 and were followed for 30 months after the procedure. ISR was defined as stenosis of at least 50% detected on angiography or ultrasonography. TVR was defined as revascularization of the treated carotid artery. During CAS, 207 patients (37.4%) were treated with cilostazol. Over 30 months, ISR occurred in 23 patients (4.2%), TVR occurred in 16 patients (2.9%), and either ISR or TVR occurred in 25 patients (4.5%). The incidence of ISR or TVR was significantly lower in the cilostazol-treated group than in the untreated group (1.4% vs 6.4%; log-rank P = .006). In a multivariate analysis, cilostazol treatment (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.08-0.95; P = .041) and stent diameter (HR, 0.73/1-mm increase; 95% CI, 0.54-0.99; P = .044) were independent factors for the occurrence of ISR or TVR. The incidence of a composite of events, including thromboembolism, hemorrhage, death, and TVR, tended to be lower in the cilostazol-treated group than in the untreated group (15.0% vs 19.9%; log-rank P = .17). Periprocedural cilostazol treatment was associated with lower rates of ISR and retreatment after CAS. A prospective randomized controlled trial is needed to clarify the effect of cilostazol on ISR after CAS., (Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.)