Predicting impaired cerebrovascular reactivity and risk of hyperperfusion syndrome in carotid artery stenosis using BeamSAT magnetic resonance imaging.

Pencil-beam presaturation (BeamSAT) magnetic resonance imaging (MRI) produces selective magnetic resonance angiography (MRA) images of specific arteries, including the unilateral internal carotid artery (ICA-selective MRA) or vertebral artery (VA-selective MRA). We evaluate the influence of flow pattern, visualized using BeamSAT MRI, on preoperative cerebral hemodynamic status and postoperative hyperperfusion syndrome (HPS). Patients undergoing carotid artery stenting or carotid endarterectomy were categorized into two groups to evaluate flow pattern. Patients with neither crossflow on BeamSAT MRI nor mismatch in middle cerebral artery (MCA) signal intensity between ICA-selective and conventional MRA were classified into Group I, comprising 29 patients. Group II included all other patients comprising 19 patients, who were suspected of experiencing changes in intracranial flow patterns. Cerebral blood flow and cerebrovascular reactivity (CVR) were assessed using single-photon emission computed tomography, and potential HPS symptoms were retrospectively assessed by chart review. Preoperative ipsilateral CVR was significantly lower in Group II than in Group I (18.0% ± 20.0% vs. 48.3% ± 19.5%; P < 0.0001). Group II showed significantly impaired CVR (odds ratio 17.7, 95% confidence interval 1.82-171; P = 0.013) in multivariate analysis. The partial areas under the curve of the BeamSAT logistic model (0.843) were significantly larger than those of the conventional logistic model (0.626) over the range of high sensitivity (0.6-1) (P = 0.04). The incidence of postoperative HPS symptoms was significantly higher in Group II than in Group I (8/19 vs. 1/29; P = 0.001). BeamSAT MRI may be a valuable and non-invasive tool for assessing cerebral hemodynamics and predicting postoperative HPS.

Successful shrinkage of a recurrent partially thrombosed symptomatic large basilar tip aneurysm using a Target 3D Coil.

Background: Standalone coil embolization is often less effective for partially thrombosed intracerebral aneurysms (PTIA) because of the risk of frequent recurrence if the coil migrates into the thrombus. This report describes a case of PTIA at the basilar tip in which simple coil embolization using a Target 3D Coil resulted in sustained remission without recurrence during long-term follow-up. Case Description: The patient was a 63-year-old male who presented with right oculomotor nerve palsy after having undergone direct surgery for a basilar artery aneurysm 15 years earlier. Recurrence with partial thrombosis of the basilar artery aneurysm was diagnosed. Target 3D Coil embolization with frame construction in the aneurysmal sac was performed, resulting in the complete disappearance of the aneurysm and improvement of the oculomotor nerve palsy. Magnetic resonance imaging at five years postoperatively confirmed that the thrombus had completely disappeared, and there was no recurrence of the aneurysm. The closed loops in the Target 3D Coil may have contributed to the cohesive mass of coils remaining in the sac of the PTIA, potentially leading to healing. Conclusion: The characteristics of the Target 3D Coil may have prevented migration of the coil into the thrombus, potentially contributing to the successful resolution of the aneurysm.

Incidence and Outcomes of Aneurysmal Subarachnoid Hemorrhage: A Multicenter Retrospective Registry-based Descriptive Trial in Kobe City.

The current study aims to evaluate the incidence and results of aneurysmal subarachnoid hemorrhage (aSAH) throughout Kobe City. Based on a multicenter retrospective registry-based descriptive trial involving all 13 primary stroke centers in Kobe City, patients with aSAH treated between October 2017 and September 2019 were studied. A total of 334 patients were included, with an estimated age-adjusted incidence of 11.12 per 100,000 person-years. Curative treatment was given to 94% of patients, with endovascular treatment (51%) preferred over surgical treatment (43%). Of the patients, 12% were treated by shunt surgery for sequential hydrocephalus with a worse outcome at 30 days or discharge (14% vs. 46%, odds ratio (OR): 0.19, 95% confidence interval (CI): 0.088-0.39, p-value <0.001). As for vasospasm and delayed cerebral ischemia, most patients were given intravenous fasudil infusion (73%), with endovascular treatment for vasospasm in 24 cases (7.2%). The fasudil group had more good outcomes (42% vs. 30%, OR: 1.64, 95% CI: 0.95-2.87, p-value = 0.075) and significantly less death (3.3% vs. 35%, OR: 0.064, 95% CI: 0.024-0.15, p-value <0.001) at 30 days or discharge. Mortality rose from 12% at 30 days or discharge to 17% at 1 year, but neurological function distribution improved over time (modified Rankin Scale 0-2 was 39% at 30 days or discharge, 53% at 60 days, and 63% at 1 year). Our retrospective registered trial presented various statistics on aSAH, summarizing the current treatment status and prognosis.

Effects of carotid revascularization on cognitive function and brain functional connectivity in carotid stenosis patients with cognitive impairment: a pilot study.

OBJECTIVE: Carotid stenosis can lead to both cognitive impairment (CI) and ischemic stroke. Although carotid revascularization surgery, which includes carotid endarterectomy (CEA) and carotid artery stenting (CAS), can prevent future strokes, its effect on cognitive function is controversial. In this study, the authors examined resting-state functional connectivity (FC) in carotid stenosis patients with CI undergoing revascularization surgery, with a particular focus on the default mode network (DMN). METHODS: Twenty-seven patients with carotid stenosis who were scheduled to undergo CEA or CAS between April 2016 and December 2020 were prospectively enrolled. A cognitive assessment, including the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Japanese version of the Montreal Cognitive Assessment (MoCA), as well as resting-state functional MRI, was performed 1 week preoperatively and 3 months postoperatively. For FC analysis, a seed was placed in the region associated with the DMN. The patients were divided into two groups according to the preoperative MoCA score: a normal cognition (NC) group (MoCA score ≥ 26) and a CI group (MoCA score < 26). The difference in cognitive function and FC between the NC and CI groups was investigated first, and then the change in cognitive function and FC after carotid revascularization was investigated in the CI group. RESULTS: There were 11 and 16 patients in the NC and CI groups, respectively. The FC of the medial prefrontal cortex with the precuneus and that of the left lateral parietal cortex (LLP) with the right cerebellum were significantly lower in the CI group than in the NC group. In the CI group, significant improvements were found in MMSE (25.3 vs 26.8, p = 0.02), FAB (14.4 vs 15.6, p = 0.01), and MoCA scores (20.1 vs 23.9, p = 0.0001) after revascularization surgery. Significantly increased FC of the LLP with the right intracalcarine cortex, right lingual gyrus, and precuneus was observed after carotid revascularization. In addition, there was a significant positive correlation between the increased FC of the LLP with the precuneus and improvement in the MoCA score after carotid revascularization. CONCLUSIONS: These findings suggest that carotid revascularization, including CEA and CAS, might improve cognitive function based on brain FC in the DMN in carotid stenosis patients with CI.

Von Hippel-Lindau disease with intracranial hemorrhage due to arteriovenous anastomosis via multiple spinal hemangioblastomas: illustrative case.

BACKGROUND: Some spinal hemangioblastomas (HBLs) resemble spinal vascular malformations. Intracranial subarachnoid hemorrhage (SAH) secondary to spinal HBL has rarely been reported. OBSERVATIONS: A 67-year-old man with a prolonged von Hippel-Lindau disease (VHL) history presented with sudden headache and vomiting. Cranial and cervical computed tomography (CT) revealed severe infratentorial, supratentorial, and cervical SAH. Cranial CT angiography and magnetic resonance imaging revealed a mismatch in hemorrhage and intracranial tumor localization, with no vascular lesions that could lead to intracranial SAH. Cervical CT angiography revealed abnormal blood vessels originating from 5 spinal tumors suspected to be HBLs. We considered that the SAH was caused by venous reflex from vascular malformation-like spinal HBLs. Transarterial embolization (TAE) of the feeding artery of HBLs was performed to improve symptoms and reduce rebleeding risk. Nine months after TAE, angiography showed no venous reflux into the intracranial space. Ten months later, the authors excised the T1-2 tumor because the patient complained of progressive paralysis of the right upper extremity. LESSONS: In HBL with prolonged VHL, intracranial hemorrhage due to venous regurgitation via a mimicked vascular malformation may occur. Reducing venous reflux with TAE may improve symptoms and prevent rebleeding.

Pseudo-continuous arterial spin labeling with short post-labeling delay time sensitively reflects the hemodynamics of symptomatic patients with permanent large vessel occlusion before and after revascularization.

BACKGROUND AND PURPOSE: This study evaluated the feasibility of arterial spin labeling (ASL) for diagnosing hemodynamic stroke due to permanent anterior circulation large vessel occlusion. METHODS: Three-dimensional pseudo-continuous ASL data at two post-labeling delay (PLD) times (1.5 and 2.5 s) in patients with unilateral permanent middle cerebral artery (MCA) segment 1 (M1) or internal cerebral artery (ICA) occlusion were acquired during routine magnetic resonance angiography. Sixty-one patients with symptomatic occlusion (M1, 24; ICA, 37) and 69 patients with asymptomatic occlusion (M1, 21; ICA, 48) were enrolled. Regions of interest were automatically placed in the MCA region using a template. The respective scans were compared with asymptomatic M1 or ICA occlusion scans. The ratio of signal intensity (occlusion side/non-occlusion side) in the perfusion area of MCA (asymmetry index [AI]) was compared between both groups. RESULTS: In both PLD groups, AI was significantly lower in symptomatic patients than in asymptomatic patients. The receiver operating characteristic curve showed moderate capacity for the prediction of symptomatic AI in both groups (area under the curve, 0.739 and 0.712, respectively). As a result of extracranial-intracranial bypass operation in 28 symptomatic (M1, eight; ICA, 20) patients, AI was significantly higher postoperatively in the PLD 1.5 s group than in the PLD 2.5 s group. CONCLUSION: In symptomatic patients with permanent large vessel occlusion, the signal intensity ratio of pseudo-continuous ASL with short PLD sensitively reflects the hemodynamics before and after revascularization; therefore, this technique may be an alternative method in situations where PET or SPECT cannot be performed.

Successful Thrombectomy for Endocarditis-Related Stroke in a Very Young Patient: Illustrative Case.

Objective: Unlike in older adults, ischemic stroke in young patients occurs secondary to preexisting conditions. Infective endocarditis (IE) is among the most important causes of stroke in young adults and has a severe prognosis. There are few reports of mechanical thrombectomy (MT) for IE-induced large-vessel occlusion (LVO). This paper reports a case of acute IE-induced LVO in a young patient who was successfully treated with MT. Case Presentation: An 18-year-old woman presented to our hospital with severe headache, high fever, and left fingertip pain. She was admitted to the Department of Neurology for conservative treatment of suspected meningitis. On day 2 of admission, she developed acute left hemiparesis, left hemispatial neglect, and dysarthria. MRA showed occlusion of the right M1 segment of the middle cerebral artery, and the patient immediately underwent MT. After a single pass, we achieved thrombolysis in cerebral infarction 2b. A white clot was diagnosed as a vegetation on pathological examination. As transesophageal echocardiography showed a vegetation on the mitral valve, the patient was diagnosed with IE and underwent cardiovascular surgery. The patient recovered well and underwent additional treatment and rehabilitation. Conclusion: Although rare, IE-induced septic emboli may occur in young patients with LVO, necessitating MT and pathological diagnosis of the clot.

Potential of machine learning to predict early ischemic events after carotid endarterectomy or stenting: a comparison with surgeon predictions.

Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are recommended for high stroke-risk patients with carotid artery stenosis to reduce ischemic events. However, we often face difficulty in determining the best treatment strategy. We aimed to develop an accurate post-CEA/CAS outcome prediction model using machine learning that will serve as a basis for a new decision support tool for patient-specific treatment planning. Retrospectively collected data from 165 consecutive patients with carotid stenosis underwent CEA or CAS and were divided into training and test samples. The following five machine learning algorithms were tuned, and their predictive performance was evaluated by comparison with surgeon predictions: an artificial neural network, logistic regression, support vector machine, random forest, and extreme gradient boosting (XGBoost). Seventeen clinical factors were introduced into the models. Outcome was defined as any ischemic stroke within 30 days after treatment including asymptomatic diffusion-weighted imaging abnormalities. The XGBoost model performed the best in the evaluation; its sensitivity, specificity, positive predictive value, and accuracy were 31.9%, 94.6%, 47.2%, and 86.2%, respectively. These statistical measures were comparable to those of surgeons. Internal carotid artery peak systolic velocity, low-density lipoprotein cholesterol, and procedure (CEA or CAS) were the most contributing factors according to the XGBoost algorithm. We were able to develop a post-procedural outcome prediction model comparable to surgeons in performance. The accurate outcome prediction model will make it possible to make a more appropriate patient-specific selection of CEA or CAS for the treatment of carotid artery stenosis.

Contribution of Endoplasmic Reticulum Stress to the Clinical Instability of Carotid Plaques in Human Carotid Stenosis.

Endoplasmic reticulum (ER) stress is an important process during the progression of atherosclerosis. The aim of this study was to elucidate the association of ER stress and clinical instability of carotid plaque. One hundred ninety-three patients with carotid stenosis undergoing carotid endarterectomies (CEAs) were enrolled. We classified the patients into 3 groups: the asymptomatic, symptomatic, and cTIA (crescendo transient ischemic attack)/SIE (stroke in evolution) groups. Immunohistological staining was performed to assess ER stress and apoptosis. The correlation between ER stress marker expression and clinical instability was analyzed by Tukey-Kramer test and ordinal logistic regression. From the 193 CEAs, 24 asymptomatic plaques and 24 symptomatic plaques were randomly selected, and all 7 plaques in the cTIA/SIE group were selected. Glycophorin A staining demonstrated significant correlation between intraplaque hemorrhage and clinical instability (odds ratio [OR], 1.27; 95%CI, 1.14-1.41). The expression of ER stress markers (glucose-regulated protein 78 [GRP78] and C/EBP homologous protein [CHOP]) exhibited a significant correlation with clinical instability (GRP78: OR, 1.25; 95%CI, 1.14-1.38, CHOP: OR, 1.39; 95%CI, 1.16-1.66). Double-label immunofluorescence demonstrated ER stress markers were detected in CD68-positive cells and smooth muscle actin (SMA)-positive cells. The coexpression of the ER stress markers exhibited a significant correlation with clinical instability (CD68/GRP78: OR, 1.13; 95%CI, 1.05-1.20, CD68/CHOP: OR, 1.092; 95%CI, 1.04-1.14, SMA/CHOP: OR, 1.082; 95%CI, 1.04-1.13). However, the colocalization of CHOP and cleaved caspase-3 (apoptosis marker) did not correlate with clinical instability. These findings indicated that the ER stress pathway may be a potential therapeutic target in the prevention of stroke.

Geranylgeranylacetone attenuates cerebral ischemia-reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study.

BACKGROUND: We previously reported that heat shock protein 27 (HSP27) phosphorylation plays an important role in the activation of glucose-6-phosphate dehydrogenase (G6PD), resulting in the upregulation of the pentose phosphate pathway and antioxidant effects against cerebral ischemia-reperfusion injury. The present study investigated the effect of geranylgeranylacetone, an inducer of HSP27, on ischemia-reperfusion injury in male rats as a preliminary study to see if further research of the effects of geranylgeranylacetone on the ischemic stroke was warranted. METHODS: In all experiments, male Wistar rats were used. First, we conducted pathway activity profiling based on a gas chromatography-mass spectrometry to identify ischemia-reperfusion-related metabolic pathways. Next, we investigated the effects of geranylgeranylacetone on the pentose phosphate pathway and ischemia-reperfusion injury by real-time polymerase chain reaction (RT-PCR), immunoblotting, and G6PD activity, protein carbonylation and infarct volume analysis. Geranylgeranylacetone or vehicle was injected intracerebroventricularly 3 h prior to middle cerebral artery occlusion or sham operation. RESULTS: Pathway activity profiling demonstrated that changes in the metabolic state depended on reperfusion time and that the pentose phosphate pathway and taurine-hypotaurine metabolism pathway were the most strongly related to reperfusion among 137 metabolic pathways. RT-PCR demonstrated that geranylgeranylacetone did not significantly affect the increase in HSP27 transcript levels after ischemia-reperfusion. Immunoblotting showed that geranylgeranylacetone did not significantly affect the elevation of HSP27 protein levels. However, geranylgeranylacetone significantly increase the elevation of phosphorylation of HSP27 after ischemia-reperfusion. In addition, geranylgeranylacetone significantly affected the increase in G6PD activity, and reduced the increase in protein carbonylation after ischemia-reperfusion. Accordingly, geranylgeranylacetone significantly reduced the infarct size (median 31.3% vs 19.9%, p = 0.0013). CONCLUSIONS: As a preliminary study, these findings suggest that geranylgeranylacetone may be a promising agent for the treatment of ischemic stroke and would be worthy of further study. Further studies are required to clearly delineate the mechanism of geranylgeranylacetone-induced HSP27 phosphorylation in antioxidant effects, which may guide the development of new approaches for minimizing the impact of cerebral ischemia-reperfusion injury.

Glioma cells require one-carbon metabolism to survive glutamine starvation.

Cancer cells optimize nutrient utilization to supply energetic and biosynthetic pathways. This metabolic process also includes redox maintenance and epigenetic regulation through nucleic acid and protein methylation, which enhance tumorigenicity and clinical resistance. However, less is known about how cancer cells exhibit metabolic flexibility to sustain cell growth and survival from nutrient starvation. Here, we find that serine and glycine levels were higher in low-nutrient regions of tumors in glioblastoma multiforme (GBM) patients than they were in other regions. Metabolic and functional studies in GBM cells demonstrated that serine availability and one-carbon metabolism support glioma cell survival following glutamine deprivation. Serine synthesis was mediated through autophagy rather than glycolysis. Gene expression analysis identified upregulation of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) to regulate one-carbon metabolism. In clinical samples, MTHFD2 expression was highest in the nutrient-poor areas around "pseudopalisading necrosis." Genetic suppression of MTHFD2 and autophagy inhibition caused tumor cell death and growth inhibition of glioma cells upon glutamine deprivation. These results highlight a critical role for serine-dependent one-carbon metabolism in surviving glutamine starvation and suggest new therapeutic targets for glioma cells adapting to a low-nutrient microenvironment.

Successful multiple burr hole openings for limb-shaking transient ischemic attack due to moyamoya disease: illustrative case.

BACKGROUND: Limb-shaking transient ischemic attacks (LS-TIAs) are a rare form of TIAs that present as involuntary movements of the limbs and indicate severe cerebral hypoperfusion. LS-TIAs are often reported in patients with carotid artery stenosis but can also affect patients with intracranial artery stenosis and moyamoya disease (MMD). OBSERVATIONS: A 72-year-old woman presented with repeated episodes of involuntary shaking movements of the right upper limb. Cerebral angiography revealed complete occlusion of the M1 segment of the left middle cerebral artery (MCA), and the left hemisphere was supplied by moyamoya vessels. She was treated with left direct revascularization without complications, and her involuntary movements subsided. However, she demonstrated involuntary shaking movements of the right lower limb 2 months postoperatively. Cerebral angiography revealed complete occlusion of the A1 segment of the left anterior cerebral artery (ACA). The multiple burr hole opening (MBHO) procedure was performed to improve perfusion in the left ACA territory and after 3 months, the patient's symptoms resolved. LESSONS: This case demonstrated that LS-TIAs can also develop as ischemic symptoms due to MMD. Moreover, instances of LS-TIA of the upper and lower limbs developed separately in the same patient. The patient's symptoms improved with direct revascularization and MBHO.

Stroke Systems of Care During the COVID-19 Epidemic in Kobe City.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) outbreak raised concerns over healthcare systems' ability to provide suitable care to stroke patients. In the present study, we examined the provision of stroke care in Kobe City during the COVID-19 epidemic, where some major stroke centers ceased to provide emergency care. METHODS: This was a cross-sectional study. The Kobe Stroke Network surveyed the number of stroke patients admitted to all primary stroke centers (PSCs) in the city between March 1 and May 23, 2020, and between March 3 and May 25, 2019. In addition, online meetings between all PSC directors were held regularly to share information. The survey items included emergency response system characteristics, number of patients with stroke hospitalized within 7 days of onset, administered treatment types (IV rt-PA, mechanical thrombectomy, surgery, and endovascular therapy), and stroke patients with confirmed COVID-19. RESULTS: During the period of interest in 2020, the number of stroke patients hospitalized across 13 PSCs was 813, which was 15.5% lower than that during the same period of 2019 (p = 0.285). The number of patients admitted with cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage decreased by 15.4% (p = 0.245), 16.1% (p = 0.659), and 14.0% (p = 0.715), respectively. However, the rates of mechanical thrombectomy and surgery for intracerebral hemorrhage were slightly increased by 12.1% (p = 0.754) and 5.0% (p = 0.538), respectively. PSCs that ceased to provide emergency care reported a decrease in the number of stroke cases of 65.7% compared with the same period in 2019, while other PSCs reported an increase of 0.8%. No case of a patient with stroke and confirmed COVID-19 was reported during the study period. CONCLUSION: Kobe City was able to maintain operation of its stroke care systems thanks to close cooperation among all city PSCs and a temporal decrease in the total number of stroke cases.

Impact of introducing endovascular treatment on acute ischemic stroke outcomes: A shift from an era of medical management to thrombectomy in Japan.

BACKGROUND: Endovascular treatment (EVT) has increasingly become the standard treatment of acute cerebral large vessel occlusion (LVO). We evaluated the impact of introducing EVT on LVO therapy in a single center where intravenous thrombolysis (IVT) had been the only recanalization therapy. MATERIALS AND METHODS: Between April 2013 and March 2017, 354 consecutive patients with LVO admitted to our institution were analyzed. We compared outcomes between two chronological groups before (Pre-EVT group) and after (Post-EVT group) introducing EVT in April 2015. We assessed prognostic factors for favorable outcomes (modified Rankin scale score ≤2 at 90 days). RESULTS: In the Pre-EVT group, all 140 patients were treated medically, including 30 patients (21%) undergoing IVT. In the Post-EVT group, 118 patients (55%) underwent EVT, and the remaining 96 patients treated medically, including six patients (3%) undergoing IVT. The proportion undergoing recanalization therapy with IVT or EVT significantly increased after introducing EVT (21% versus 58%, p < 0.001). The rate of patients achieving favorable outcomes also significantly increased (14% versus 31%, p < 0.001). In multivariate regression analysis, introducing EVT was an independent predictive factor after adjusting for age, stroke severity and extent, and time (p = 0.005). The arrival time in patients with helicopter transport was significantly shorter than that with ground ambulance for a distance of more than 10 km (p < 0.001). CONCLUSIONS: This study demonstrated that the introduction of EVT improved outcomes of acute LVO patients, increasing the opportunity to receive recanalization therapy. Further efforts to establish medical systems to provide EVT are required throughout the country.

Outcome and effect of endovascular treatment in stroke associated with acute extracranial internal carotid artery occlusion: Single-center experience in Japan.

BACKGROUND: Positive data from several randomized controlled trials (RCTs) of endovascular treatment (EVT) for acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion (ACLVO) have emerged. However, little evidence exists on EVT for acute extracranial internal carotid artery (EC-ICA) occlusion. We therefore analysed the outcome and effect of EVT on AIS due to ACLVO caused by EC-ICA occlusion, including tandem occlusion compared with that caused by pure intracranial artery occlusion. METHODS: A total of 135 consecutive AIS patients with ACLVO between July 2014 and December 2017 were identified. We retrospectively analysed the efficacy of EVT for ACLVO after introducing a stent retriever (SR). We classified ACLVO into the following categories: group A, intracranial artery occlusion without EC-ICA occlusion (pure intracranial artery occlusion), and group B, ipsilateral EC-ICA occlusion with/without intracranial artery occlusion. RESULTS: In total, 65 patients were enrolled. Group A comprised 71% (46/65) of all cases. No difference was observed in terms of age, National Institute of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early Computed Tomography Score-Diffusion Weighted imaging (ASPECTS-DWI), several clinical time intervals, rate of successful revascularization (74% versus 84%), and rate of functional independence (42% versus 39%) between groups A and B. In all patients, an ASPECTS-DWI ≥6 and an onset-to-door time ≤6 h were associated with good outcome, whereas intracranial artery occlusion without EC-ICA occlusion (pure intracranial artery occlusion) was not. CONCLUSIONS: The outcomes support the efficacy of EVT in stroke associated with acute EC-ICA occlusion. In the EVT of AIS due to ACLVO, there was no significant difference in the results between ipsilateral EC-ICA occlusion with/without intracranial artery occlusion and intracranial artery occlusion without EC-ICA occlusion (pure intracranial artery occlusion).

Pencil Beam Presaturation Magnetic Resonance Imaging Helps to Identify Patients at Risk for Intolerance to Temporary Internal Carotid Artery Occlusion During Carotid Endarterectomy and Carotid Artery Stenting.

BACKGROUND: There has been no effective method to predict ischemic intolerance to temporary internal carotid artery (ICA) occlusion during carotid artery reconstruction. Pencil beam presaturation (BeamSAT) pulse suppresses the flow signal of the target vessel in magnetic resonance angiography (MRA). Applying this method, we constructed ICA-selective MRA images. The aim of this study was to identify patients at risk for ischemic intolerance by ICA-selective MRA. METHODS: By evaluating flow of anterior communicating artery (Acom) and A1 portion of anterior cerebral artery with ICA-selective MRA and posterior communicating artery (Pcom) with conventional MRA, we investigated associations of these collateral flow patterns with ischemic intolerance and decrease of regional cerebral oxygen saturation. RESULTS: The study included 58 patients who underwent carotid endarterectomy or carotid artery stenting. Six of 7 patients without Acom flow and Pcom flow demonstrated ischemic intolerance, whereas all patients (n = 51) with Acom and/or Pcom flow demonstrated tolerance. The accuracy of this prediction model according to Acom and Pcom flow patterns for ischemic intolerance was 0.98 (P = 0.01, binomial test). Regional cerebral oxygen saturation decrease after ICA occlusion was significantly larger in patients without Acom flow and Pcom flow (12.0% ± 6.0%) than in patients with Acom flow and Pcom flow (3.0% ± 3.1%, P < 0.01) and in patients with Acom flow but no Pcom flow (2.4% ± 5.2%, P < 0.01). CONCLUSIONS: These findings support the importance of Acom flow as a collateral route. ICA-selective MRA enables prediction of ischemic intolerance to temporary ICA occlusion during carotid endarterectomy or carotid artery stenting. This method provides valuable information regarding probability of an ischemic complication.

MicroRNA regulating stanniocalcin-1 is a metastasis and dissemination promoting factor in glioblastoma.

BACKGROUND: MicroRNAs (miRs) regulate many biological processes, such as invasion, angiogenesis, and metastasis. Glioblastoma (GBM) patients with metastasis/metastatic dissemination have a very poor prognosis; therefore, inhibiting metastasis/metastatic dissemination has become an important therapeutic strategy for GBM treatment. METHODS: Using 76 GBM tissues, we examined the expression levels of 23 GBM-related miRs and compared the miRs' expression levels between GBMs with metastasis/metastatic dissemination and GBMs without metastasis/metastatic dissemination. Using the bioinformatics web site, we searched the target genes of miRs. To analyze the function of target gene, several biological assays and survival analysis by the Kaplan-Meier method were performed. RESULTS: We found that eight miRs were significantly decreased in GBM with metastasis/metastatic dissemination. By the bioinformatics analysis, we identified stanniocalcin-1 (STC1) as the most probable target gene against the combination of these miRs. Four miRs (miR-29B, miR-34a, miR-101, and miR-137) have predictive binding sites in STC1 mRNA, and mRNA expression of STC1 was downregulated by mimics of these miRs. Also, mimics of these miRs and knockdown of STC1 by siRNA suppressed invasion in GBM cells. GBM with metastasis/metastatic dissemination had significantly higher levels of STC1 than GBM without metastasis/metastatic dissemination. Finally, Kaplan-Meier analysis demonstrated that GBMs with high STC1 level had significantly shorter survival than GBMs with low STC1 level. CONCLUSIONS: STC1 may be a novel metastasis/metastatic dissemination promoting factor regulated by several miRs in GBM. Because STC1 is a secreted glycoprotein and functions via the autocrine/paracrine signals, inhibiting STC1 signal may become a novel therapeutic strategy for GBM.

Detection of Hemodynamic Characteristics Before Growth in Growing Cerebral Aneurysms by Analyzing Time-of-Flight Magnetic Resonance Angiography Images Alone: Preliminary Results.

OBJECTIVE: Cerebral aneurysm growth often precedes rupture. Definite contributors to aneurysm growth have not been determined even by means of recently developed commercially available computational fluid dynamics (CFD) software. We developed an original CFD tool that can analyze data from time-of-flight magnetic resonance angiography (TOF-MRA) before growth in the growing aneurysms and investigate possible factors for aneurysm growth in the near future. METHODS: We retrospectively reviewed unruptured aneurysms that were treated at our institute because of aneurysm growth (growing group) between April 2013 and March 2017. Stable aneurysms that had demonstrated no growth for more than 5 years were selected (stable group). TOF-MRA data of these aneurysms were retrospectively converted to 3-dimensional vessel geometric data; 3 hemodynamic indices including streamline, wall shear stress (WSS), and oscillatory shear index were calculated by our original CFD tool using the lattice Boltzmann method to quantitatively compare the 2 groups. RESULTS: Six growing aneurysms and 6 stable aneurysms were analyzed. Of the 6 growing aneurysms, WSS on the focal aneurysmal sac increased temporally in the vicinity of the constant low WSS area at the peak systolic phase. By contrast, WSS did not increase during any part of the cardiac cycle in 3 of the 6 stable aneurysms. The peak values of WSS were significantly different between the 2 groups. CONCLUSIONS: A focal increase in WSS in the peak systolic phase may be a risk factor for aneurysm enlargement in the near future.

Pentose phosphate pathway activation via HSP27 phosphorylation by ATM kinase: A putative endogenous antioxidant defense mechanism during cerebral ischemia-reperfusion.

Molecular mechanism underlying ischemic stroke remains poorly understood. We previously reported glucose 6-phosphate dehydrogenase (G6PD) activity in pentose phosphate pathway (PPP) is activated via heat shock protein 27 (HSP27) phosphorylation at serine 85 (S85) by ataxia telangiectasia mutated (ATM) kinase during cerebral ischemia. This mechanism seems to be endogenous antioxidative system. To determine whether this system also works during reperfusion, we performed comparative metabolic analysis of reperfusion effect on metabolism in rat cortex using middle cerebral artery occlusion (MCAO). Metabolic profiling using gas-chromatography/mass-spectrometry analysis showed changes in metabolic state that depended on reperfusion time. Enrichment analysis showed PPP was significantly upregulated during ischemia-reperfusion. Significant increases in fructose 6-phosphate and ribulose 5-phosphate after reperfusion also suggested enhancement of PPP. In relation to PPP, ischemia-reperfusion induced an increase of up to 69-fold in HSP27 transcripts after 24-h reperfusion. Immunoblotting showed gradual increase in HSP27 protein and marked increase in HSP27 phosphorylation (S85) that were time-dependent (4.5-fold after 24-h reperfusion). G6PD activity was significantly elevated after 1-h MCAO (20%), reduced after 1-h reperfusion, increased gradually thereafter and significantly elevated after 24-h reperfusion. The NADPH/NAD+ ratio displayed similar increasing pattern. Intracerebroventricular injection of ATM kinase inhibitor (KU-55933) significantly reduced HSP27 phosphorylation and G6PD activity, significantly increased protein carbonyl, and resulted in increase in infarct size (100%) 24-h after reperfusion following 90-min MCAO. Consequently, G6PD activation via HSP27 phosphorylation by ATM kinase may be part of endogenous antioxidant defense neuroprotection mechanism that is activated during ischemia-reperfusion. These findings have important implications for treatment of stroke.

Novel Segmentation of Placed Coils in the Treatment of Cavernous Sinus Dural Arteriovenous Fistulas Provides a Reliable Predictor of the Long-Term Outcome in Abducens Nerve Palsy.

OBJECTIVE: Abducens nerve palsy (ANP) after transvenous embolization (TVE) for cavernous sinus (CS) dural arteriovenous fistulas (DAVFs) sometimes persists. The aim of this study was to assess the correlation between the coil mass and the long-term outcome of ANP after TVE. METHODS: Between January 2008 and July 2016, 33 patients with a CS DAVF underwent TVE at our institute. On the basis of the relationship to the internal carotid artery (ICA), we divided the lateral part of the CS into the following 3 portions: anterolateral, anterolateral to the anterior bend of the ICA; middle-lateral (ML), lateral to the horizontal segment of the ICA; and posterolateral, posterolateral to the posterior bend of the ICA. RESULTS: ANP persisted in 4 patients. The number of coils (35.3 vs. 21.9 coils; P = 0.04), coil volume (198.4 vs. 103.6 mm3; P = 0.03), and coil volume in the ML (54.9 vs. 20.3 mm3; P = 0.01) were significantly greater in the ANP group than in the non-ANP group. In the logistic regression analysis, only the ML coil volume was significantly associated with the persistence of ANP (P = 0.04). Based on the receiver operating characteristic curve, the optimal cutoff value of the ML coil volume was 27.9 mm3 (sensitivity, 100%; specificity, 72.4%). CONCLUSIONS: Overpacking in the ML of the CS should be avoided to prevent persistent ANP. The cutoff value of the ML coil volume may provide a good guide for the practical use of TVE for CS DAVFs.