Utility of intraoperative magnetic resonance imaging for giant cell tumor of bone after denosumab treatment: a pilot study.

BACKGROUND: Giant cell tumor of bone (GCTB) is an intermediate but locally aggressive neoplasm. Current treatment of high-risk GCTB involves administration of denosumab, which inhibits bone destruction and promotes osteosclerosis. However, denosumab monotherapy is not a curative treatment for GCTB and surgical treatment remains required. Denosumab treatment complicates surgery, and the recurrence rate of GCTB is high (20%-30%). PURPOSE: To examine the utility of intraoperative magnetic resonance imaging (iMRI) for detection and reduction of residual tumor after denosumab treatment and to investigate the utility of iMRI, which is not yet widely used. MATERIAL AND METHODS: We enrolled five patients who received denosumab for a median period of eight months (range 6-12 months). Surgery was performed when the degree of osteosclerosis around the articular surface was deemed appropriate. We performed iMRI using a modified operation table to identify residual tumor after initial curettage and evaluated the rate of detection of residual tumor by iMRI, intraoperative and postoperative complications, exposure time of iMRI, and operation time. RESULTS: Suspected residual tumor tissue was identified in all five cases and was confirmed by histopathology after additional curettage. The rate of detection of residual tumor by iMRI was 100%. Residual tumor was located in sites which were difficult to remove due to osteosclerosis. The iMRI was performed safely and without trouble. During the median follow-up period of 10 months (range 6-24 months), no adverse events or recurrences occurred. CONCLUSION: Intraoperative MRI could contribute to the reduction of residual tumor tissue and it may prevent recurrence of GCTB after denosumab therapy.

Visualisation of the non-linear correlation between age and poor outcome in patients with aneurysmal subarachnoid haemorrhage.

OBJECTIVE: To visualise the non-linear correlation between age and poor outcome at discharge in patients with aneurysmal subarachnoid haemorrhage (SAH) while adjusting for covariates, and to address the heterogeneity of this correlation depending on disease severity by a registry-based design. METHODS: We extracted data from the Japanese Stroke Databank registry for patients with SAH treated via surgical clipping or endovascular coiling within 3 days of SAH onset between 2000 and 2017. Poor outcome was defined as a modified Rankin Scale Score ≥3 at discharge. Variable importance was calculated using machine learning (random forest) model. Correlations between age and poor outcome while adjusting for covariates were determined using generalised additive models in which spline-transformed age was fit to each neurological grade of World Federation of Neurological Societies (WFNS) and treatment. RESULTS: In total, 4149 patients were included in the analysis. WFNS grade and age had the largest and second largest variable importance in predicting the outcome. The non-linear correlation between age and poor outcome was visualised after adjusting for other covariates. For grades I-III, the risk slope for unit age was relatively smaller at younger ages and larger at older ages; for grade IV, the slope was steep even in younger ages; while for grade V, it was relatively smooth, but with high risk even at younger ages. CONCLUSIONS: The clear visualisation of the non-linear correlation between age and poor outcome in this study can aid clinical decision making and help inform patients with aneurysmal SAH and their families better.

The right hemisphere is important for driving-related cognitive function after stroke.

Considering quality of life (QOL) after stroke, car driving is one of the most important abilities for returning to the community. In this study, directed attention and sustained attention, which are thought to be crucial for driving, were examined. Identification of specific brain structure abnormalities associated with post-stroke cognitive dysfunction related to driving ability would help in determining fitness for car driving after stroke. Magnetic resonance imaging was performed in 57 post-stroke patients (51 men; mean age, 63 ± 11 years) who were assessed for attention deficit using a standardized test (the Clinical Assessment for Attention, CAT), which includes a Continuous Performance Test (CPT)-simple version (CPT-SRT), the Behavioral Inattention Test (BIT), and a driving simulator (handle task for dividing attention, and simple and selective reaction times for sustained attention). A statistical non-parametric map (SnPM) that displayed the association between lesion location and cognitive function for car driving was created. From the SnPM analysis, the overlay plots were localized to the right hemisphere during handling the hit task for bilateral sides (left hemisphere damage related to right-side neglect and right hemisphere damage related to left-side neglect) and during simple and selective reaction times (false recognition was related to damage of both hemispheres). A stepwise multiple linear regression analysis confirmed the importance of both hemispheres, especially the right hemisphere, for cognitive function and car driving ability. The present study demonstrated that the right hemisphere has a crucial role for maintaining directed attention and sustained attention, which maintain car driving ability, improving QOL for stroke survivors.

Genetic analysis in patients with newly diagnosed glioblastomas treated with interferon-beta plus temozolomide in comparison with temozolomide alone.

PURPOSE: This study aimed to explore the genetic alterations and to identify good responders in the experimental arm in the tumor samples from newly diagnosed glioblastoma (GBM) patients enrolled in JCOG0911; a randomized phase II trial was conducted to compare the efficacy of interferonß (IFNß) plus temozolomide (TMZ) with that of TMZ alone. EXPERIMENTAL: DESIGN: Of 122 tumors, we performed deep targeted sequencing to determine the somatic mutations, copy number variations, and tumor mutation burden; pyrosequencing for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation; Sanger sequencing for the telomerase reverse transcriptase (TERT) promoter; and microsatellite instability (MSI) testing in 95, 91, 91 and 72 tumors, respectively. We performed a multivariable Cox regression analysis using backward stepwise selection of variables including clinical factors (sex, age, performance status, residual tumor after resection, tumor location) and genetic alterations. RESULTS: Deep sequencing detected an IDH1 mutation in 13 tumors (14%). The MGMT promoter methylation by quantitative pyrosequencing was observed in 41% of the tumors. A mutation in the TERT promoter was observed in 69% of the tumors. While high tumor mutation burden (> 10 mutations per megabase) was seen in four tumors, none of the tumors displayed MSI-high. The clinical and genetic factors considered as independent favorable prognostic factors were gross total resection (hazard ratio [HR]: 0.49, 95% confidence interval, 0.30-0.81, P = 0.0049) and MGMT promoter methylation (HR: 0.43, 0.21-0.88, P = 0.023). However, tumor location at the temporal lobe (HR: 1.90, 1.22-2.95, P = 0.0046) was an independent unfavorable prognostic factor. No predictive factors specific to the TMZ + IFNß + Radiotherapy (RT) group were found. CONCLUSION: This additional sub-analytical study of JCOG0911 among patients with newly diagnosed GBM showed that tumor location at the temporal lobe, gross total resection, and MGMT promoter methylation were significant prognostic factors, although no factors specific to IFNß addition were identified.

Preoperative sensory aura predicts risk for seizure in temporal lobe epilepsy surgery.

BACKGROUND: Patients with temporal lobe epilepsy (TLE) often report viscerosensory and experiential auras, with substantial epilepsy localization. However, few previous studies have investigated the epileptic preoperative aura, particularly with regard to its effect on surgical outcomes in patients with drug-resistant epilepsy. OBJECTIVE: This study investigated the potential role of preoperative aura in predicting outcomes after surgery for TLE. MATERIAL AND METHODS: This study included consecutive patients diagnosed with TLE who underwent anterior temporal lobectomy (ATL) for drug-resistant TLE during the period from January 1999 to December 2017. Data pertaining to patient age at the time of surgery, sex, age at initial seizure onset, duration of epilepsy, presence of preoperative aura, comprehensive clinical semiology, side of surgery, and type of pathology were analyzed. Preoperative auras were classified as autonomic, sensory, mental and affective, or multiple manifestations. Patients were followed at 3 and 12 months after surgery and at regular intervals thereafter. RESULTS AND CONCLUSIONS: A total of 498 patients were included in the study. Positive preoperative aura was observed in 386 patients (77.51%). The correlation of each variable with seizure outcomes was analyzed, and the only variable found to correlate with seizure outcome was the presence of preoperative aura. Compared with those with negative preoperative aura, those with positive preoperative aura were 1.74-fold more likely to be seizure-free after surgery for TLE. The analysis of patient data suggested a later onset of initial seizure in those with positive preoperative aura, compared with those without (p = 0.04, 95% confidence interval (CI): 0.55-3.24). Patients with a shorter duration of disease prior to TLE surgery were more likely to achieve seizure-free status postoperatively. Preoperative sensory aura was a good predictor that a patient would be seizure-free during follow-up (p = 0.022).

Stenting for Innominate Artery Stenosis Under Double-Filter Protection of the Anterior and Posterior Circulation via the Right Brachial Artery.

Several protocols for angioplasty and stenting for stenosis of an innominate artery (IA) are reported, but the protocols are sometimes complicated and have disadvantages. We report a case of IA stenosis presenting ischemic symptoms in a 58-year-old woman. Stenting for the IA stenosis was performed through the right femoral artery. The cerebral protection was placed via the right brachial artery, with a filter at the right internal carotid artery and another filter at the right vertebral artery. The symptomatic IA stenosis was resolved without any complications. Regardless of the direction of blood flow, simultaneous protection of both the anterior and posterior cerebral circulation is necessary during IA stenting. Double-filter protection can provide excellent cerebral protection during an IA stenting procedure.

Pediatric pial arteriovenous fistula located at the bottom of the callosal sulcus presenting with intraventricular hemorrhage: a case report and literature review.

BACKGROUND: A pial arteriovenous fistula (pAVF) is a rare condition characterized by a direct connection between a cerebral artery and cerebral vein without an intervening nidus. The prognosis is poor in untreated cases with hemorrhagic manifestations, indicating that surgical treatment is desirable. We describe a successful endovascular treatment for a pediatric case of ruptured pAVF located at the bottom of the sulcus. CLINICAL DESCRIPTION: An 11-year-old girl presented with severe headache and mild disturbance of consciousness. Head computed tomography showed hemorrhage in the callosal sulcus and ventricle. Cerebral angiography showed an arteriovenous shunt without a nidus. The branching artery from the pericallosal artery was connected directly to the thalamostriate vein without varix, and the shunt point was located at the bottom of the callosal sulcus. The patient was diagnosed with pAVF involving a single feeder and single drainer. Emergency endovascular transarterial embolization was performed using 20% N-butyl cyanoacrylate, and the shunt disappeared completely without complications. The patient was discharged with no neurological deficits. CONCLUSION: Endovascular treatment is feasible, safe, and effective for pediatric cases of deeply located pAVF.

Bevacizumab for optic pathway glioma with worsening visual field in absence of imaging progression: 2 case reports and literature review.

Children with optic pathway gliomas (OPGs) frequently suffer from problems of visual function resulting from tumors. Previous reports showed that bevacizumab improved visual function in patients with OPG via tumor response to treatment. In these two case reports, we show that bevacizumab improved visual field without tumor response as seen in imaging. Both, a 10-year-old girl and a 6-year-old boy, had previous history of treatment with platinum-based chemotherapy. They had visual deterioration without tumor progression on MR imaging. Bevacizumab effectively and immediately improved visual field in both patients without imaging response of OPG. We emphasize that bevacizumab should be considered for patients with OPGs having visual deterioration without tumor progression.

In-hospital mortality and poor outcome after surgical clipping and endovascular coiling for aneurysmal subarachnoid hemorrhage using nationwide databases: a systematic review and meta-analysis.

There has never been evidence for aneurysmal subarachnoid hemorrhage (aSAH) by endovascular coiling compared to surgical clipping with all grade. The present study and meta-analysis aimed to clarify the in-hospital mortality and poor outcome in the nationwide databases of patients with all grade aSAH between them. The outcome of modified Rankin scale (mRS) at discharge was investigated according to the comprehensive nationwide database in Japan. The propensity score-matched analysis was conducted among patients with aSAH in this database registered between 2010 and 2015. Meta-analysis of studies was conducted based on the nationwide databases published from 2007 to 2018. According to this propensity score-matched analysis, no significant association for poor outcome of mRS > 2 was shown between surgical clipping and endovascular coiling (47.7% vs 48.3%, p = 0.48). However, significantly lower in-hospital mortality was revealed after surgical clipping than endovascular coiling (7.1% vs 12.2%, p < 0.001). Meta-analysis of propensity score-matched analysis in the nationwide database showed no significant association for poor outcome at discharge between them (odds ratio [OR], 1.08; 95% confidence interval [CI], 0.93 to 1.26; p = 0.31). Meta-analysis of propensity score-matched analysis for in-hospital mortality was lower after surgical clipping than after endovascular coiling, however, without significant difference (OR, 0.74; 95% CI, 0.52 to 1.04; p = 0.08). Further prospective randomized controlled study with all grade aSAH should be necessary to validate the in-hospital mortality and poor outcome.

Radiological and Immunostaining Characteristics of H3.3 G34R-Mutant Glioma: A Report of 3 Cases and Review of the Literature.

INTRODUCTION: H3.3 G34R/V mutation is predominantly identified in the supratentorial nonmidline tumors. However, this tumor is not yet categorized as an entity in 2016 WHO CNS classification. More information is necessary to further determine the characteristics of this tumor. CASE PRESENTATION: Three cases of adolescent hemispheric glioma were treated in our institution. All tumors showed the characteristics of huge tumor size with mild peritumoral edema on T2WI/FLAIR, hyperintense on DWI, and slight partial enhancement by gadolinium. The single-voxel proton MR spectroscopy revealed characteristics of high choline peak, marked decrease in N-acetyl aspartate peak, and small lactate peak. The histopathological diagnosis, based on 2007 WHO CNS classification, was high-grade glioma in 2 cases and a PNET. Immuno-staining revealed that the tumor cells were positive against H3.3 G34R, H3K27me3, and p53 antibodies and negative against H3K27M, IDH1-R132H, ATRX, and Olig2 antibodies. Pyrosequencing analysis confirmed H3.3 G34R mutation, IDH-wildtype, and BRAF-wildtype. CONCLUSION: Radiological and immunostaining findings are characteristic in our 3 cases of H3.3 G34-mutant glioma. It is essential to consider H3.3 G34-mutant glioma as a differential diagnosis particularly in pediatric and adolescents and young adult hemispheric tumors.

Early venous filling after reperfusion therapy in acute ischemic stroke.

BACKGROUND AND PURPOSE: Early venous filling after endovascular mechanical thrombectomy in acute ischemic stroke (AIS) is a specific finding that may serve as a biomarker for intracranial hemorrhage. However, the pathophysiology of early venous filling and postoperative hemorrhage remains unclear. The aim of this study was to investigate correlation between early venous filling and various factors involving patient demographics and perioperative imaging. METHODS: We prospectively analyzed 35 patients with AIS due to cardioembolism (CE) who underwent successful acute revascularization (TICI ≥2). Ischemic lesions were scored by magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI). Outcomes were assessed using the modified Rankin Scale (mRS) 90 days after stroke onset. Blood flow analysis was evaluated by MRI with arterial spin labeling (ASL). Early venous filling was assessed by digital subtraction angiography (DSA). Univariate analysis was performed to investigate correlations between early venous filling and patient demographics and imaging findings. RESULTS: Early venous filling was observed in 22 of 35 (66%) patients after reperfusion therapy. There was a significant correlation between early venous filling and DWI-ASPECTS (6.2 vs 8.8, p=0.0003), outcome (5 vs 9, p=0.006), hyperperfusion (17 vs 1, p< 0.0001), and hemorrhagic transformation (17 vs 1, p=0.005). CONCLUSIONS: This comprehensive study revealed that early venous filling after reperfusion therapy is associated with postoperative hyperperfusion. Early venous filling may be a marker of the process of hyperperfusion, leading to hemorrhage and an unfavorable outcome. Detection of early venous filling may be an important finding on DSA for subsequent intensive perioperative management.

Blood Flow Pattern Analysis for Carotid Plaque Evaluation.

BACKGROUND AND PURPOSE: Previous studies suggested that turbulent flow is closely related to plaque vulnerability. Two-dimensional (2D) flow analysis is a novel modality that enables real-time blood flow analysis by picturing particle movement in the contrast medium. We evaluated flow patterns in the carotid plaque to investigate the correlation between blood flow and plaque vulnerability. MATERIAL AND METHODS: A total of 36 consecutive patients with cervical carotid artery stenosis were evaluated. The flow pattern of carotid artery stenosis was evaluated using 2D real-time flow analysis in the digital subtraction angiography (DSA). The flow pattern was classified into either turbulent or laminar flow as vectors. Plaque vulnerability was evaluated on MR plaque imaging. Univariate analysis was performed to assess the correlation between the flow pattern and plaque features. RESULTS: The turbulent pattern was identified in 28 of 36 plaques (77.8%). Turbulence around plaques was significantly associated with Gadolinium enhancement (P = .0004). The maximum degree of stenosis (P = .0005) and concomitant ulceration (P = .02) were significantly associated with the turbulent pattern. There was no relationship between the turbulent pattern and clinical neurological symptoms. CONCLUSIONS: In the present study, the majority of carotid plaques exhibited a turbulent flow pattern, which was significantly associated with Gadolinium enhancement on MR plaque imaging and morphologic factors. Thus, real-time flow analysis may clarify the pathophysiology of plaque instability and the formation of ulceration.

Aging Changes of Aneurysmal Subarachnoid Hemorrhage: A 35-year, Hospital-Based Study.

BACKGROUND: The etiology and background factors which cause decreases in the size of ruptured intracranial aneurysms remain unclear. OBJECTIVE: To clarify the age- and sex-related differences in aneurysmal subarachnoid hemorrhage (SAH) based on a 35-year-old hospital database and demographic data. METHODS: A database of patients admitted to our hospital with aneurysmal SAH from 1983 to 2017 was split into 5-year intervals and analyzed. Demographic data of the general population were also analyzed for reference. RESULTS: Altogether, 1,523 aneurysmal SAH events were enrolled in the analysis. Age (p<0.001), proportion of elderly patients ≥ 65 years old (p<0.001), female sex (p=0.005), very small aneurysms less than 5 mm (p<0.001), and the yearly-averaged number of fatal events showed increasing trends. The proportion of aneurysm size of 10 mm or more (p = 0.011) and the yearly-averaged population of Shimane prefecture (p < 0.001) showed declining trends. In the subgroup analyses, the proportion of very small aneurysms was found to increase significantly in the non-elderly male and elderly female subgroups. The proportion of large aneurysms (10 mm or more) decreased in the non-elderly subgroup (p<0.05). As for the elderly subgroups, the yearly-averaged number of events did not show a significant tendency, although the yearly-averaged population of Shimane prefecture showed an increasing trend. CONCLUSION: We found an increasing trend in the prevalence of very small aneurysms in elderly females. Recent aging may contribute to this trend. The number of aneurysmal SAH events was confirmed to not increase, despite the increased aging population of Shimane prefecture.

Magnetic resonance vessel wall imaging predicts morphological deterioration in unruptured intracranial artery dissection.

OBJECTIVE: The mechanism involved in progression of unruptured intracranial artery dissection (IAD) is poorly understood. We investigated the relationship between contrast enhancement of dissecting lesions on magnetic resonance vessel wall imaging (MR-VWI) and unruptured IAD progression on the hypothesis that this finding might predict its instability. METHODS: A total of 49 unruptured IADs were investigated retrospectively. Three-dimensional T1-weighted fast spin-echo sequences were obtained before and after injection of contrast medium, and the dissecting lesion/pituitary stalk contrast enhancement ratio (CRstalk) was calculated. Unruptured IAD progression was defined as morphological deterioration; progressive dilatation or stenosis. The relations between unruptured IAD progression and potential risk factors were statistically investigated. RESULTS: Morphological deterioration was demonstrated in eleven of 49 unruptured IADs (22 %). The CRstalk value and male predominance was significantly higher in progressed IADs than stable ones (1.0 vs. 0.65; p = 0.0035, 82% vs 37%; p= 0.015, respectively). On stepwise multivariable logistic regression analysis, the CRstalk value was independently associated with unruptured IAD progression with odds ratio of 102.5 (95% CI, 2.59-4059, P=0.0013). The optimal cutoff value of CRstalk to estimate IADs with progression was 0.87 (sensitivity, 0.82; specificity, 0.74). Multimodalic images showed contrast enhancement on VWI corresponded to residual stagnant flow in dissecting lesions. CONCLUSIONS: Quantitative analysis of contrast enhancement on VWI could predict instability of unruptured IADs. Contrast enhancement in dissecting lesions would be a clue to understand the mechanism of unruptured IAD progression.

Vessel Wall Imaging of Evolving Unruptured Intracranial Aneurysms.

Background and Purpose- Unruptured intracranial aneurysms (UIAs) have various scenarios of growth and rupture. Magnetic resonance vessel wall imaging can detect aneurysmal wall thickening with inflammation and neovascularization. This study was performed to explore the vessel wall imaging findings of UIAs with consecutive follow-up. Methods- A total of 60 aneurysms with serial angiography over 2 years (mean period, 49 months, range, 24-192 months) were evaluated by vessel wall imaging. UIAs were morphologically categorized into 3 patterns: stable, whole sac expansion, or daughter sac formation. Aneurysm wall enhancement (AWE) was evaluated after administration of gadolinium. Results- Thirty-three of the 60 UIAs (55%) demonstrated no morphological changes, whereas 16 UIAS (27%) showed whole sac expansion and 11 UIAs (18%) demonstrated daughter sac formation. AWE was significantly less frequent in stable UIAs compared with UIAs showing morphological changes ( P<0.01). Aneurysms with daughter sac formation showed a significantly higher frequency of AWE than those demonstrating whole sac expansion. In the majority of UIAs with daughter sac formation, AWE was detected in the main aneurysm and not in the developing component. Conclusions- UIAs demonstrate various modes of growth. The pattern of AWE might be useful for identifying unfavorable morphological changes of UIAs.

Neointimal formation after carotid artery stenting: phantom and clinical evaluation of model-based iterative reconstruction (MBIR).

OBJECTIVES: The objective of this study was to investigate the usefulness of model-based iterative reconstruction (IR) for detecting neointimal formations after carotid artery stenting. METHODS: In a cervical phantom harbouring carotid artery stents, we placed simulated neointimal formations measuring 0.40, 0.60, 0.80 and 1.00 mm along the stent wall. The thickness of in-stent neointimal formations was measured on images reconstructed with filtered-back projection (FBP), hybrid IR (AIDR 3D), and model-based IR (FIRST). The clinical study included 43 patients with carotid stents. Cervical computed tomography (CT) images obtained on a 320-slice scanner were reconstructed with AIDR 3D and FIRST. Five blinded observers visually graded the likelihood of neointimal formations on AIDR 3D and AIDR 3D plus FIRST images. Carotid ultrasound images were the reference standard. We analysed results of visual grading by using a Jack-knife type receiver observer characteristics analysis software. RESULTS: In the phantom study, the difference between the measured and the true diameter of the neointimal formations was smaller on FIRST than FBP or AIDR 3D images. In the clinical study, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of AIDR 3D were 58%, 88%, 83%, 67% and 73%, respectively. For AIDR 3D plus FIRST images they were 84%, 78%, 80%, 82% and 81%, respectively. The mean area under the curve was significantly higher on AIDR 3D plus FIRST than AIDR 3D images (0.82 vs 0.72; p < 0.01). CONCLUSIONS: The model-based IR algorithm helped to improve diagnostic performance for the detection of neointimal formations after carotid artery stenting. KEY POINTS: • Neointimal formations can be visualised more accurately with model-based IR. • Model-based IR improves the detection of neointimal formations after carotid artery stenting. • Model-based IR is suitable for follow up after carotid artery stenting.

Immunostaining of Increased Expression of Enhancer of Zeste Homolog 2 (EZH2) in Diffuse Midline Glioma H3K27M-Mutant Patients with Poor Survival.

INTRODUCTION: The interaction of K27M mutation in histone H3 (H3K27M mutation) with polycomb repressive complex 2 (PRC2) is facilitated by the enhancer of zeste homolog 2 (EZH2). Subsequently, this interaction leads to the global reduction level of H3K27me3. We analyzed the EZH2 expression level in H3K27M mutation-positive tumors and revealed the association of high EZH2 expression with poor survival. METHODS: Our study included 12 patients, with an age range of 6-56 years and treated between 2007 and 2016. All patients underwent MRI study for nonenhanced T1, T2, diffusion, gadolinium-enhanced T1-weighted imaging, and fluid-attenuated inversion recovery (FLAIR). Immunohistochemical staining was performed against H3K27M, H3K27me3, EZH2, EED, mutant isocitrate dehydrogenase 1 (IDH1), α-thalassemia X-linked intellectual disability (ATRX), p53, O6-methylguanine-DNA methyltransferase (MGMT), and Ki-67 antibodies. RESULTS: All patients were negative for IDH1R132H and H3K27me3, but H3K27M-positive. Staining against EZH2 was negative in all histological features of grade II cases (3/12) and positive in grade III and IV cases; EZH2 positivity is associated with poor prognosis (p = 0.0082). EZH2 positivity was not associated with EED positivity. Retained ATRX staining was found mostly in grade III and IV cases (6/12). P53 was predominantly positive in cases of astrocytoma and glioblastoma (8/12). The labeling index of Ki-67 was 1.2-31.4% for grade II and III histological features and 11.2-24.8% for grade IV. CONCLUSION: We suggest that the expression of EZH2 is not associated with the PRC2 pathway and increases in patients with H3K27M-mutant diffuse midline glioma and a poor prognosis. Further studies are necessary to understand the mechanism involved.

Hyperperfusion after Endovascular Reperfusion Therapy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Patients with acute ischemic stroke (AIS) may display prolonged neurological deficits and conscious disturbance even after successful endovascular thrombectomy. We hypothesized that hemodynamic change after reperfusion might influence outcomes. This study investigated the factors causing hyperperfusion and outcomes. METHODS: We retrospectively analyzed 27 patients with AIS who underwent successful acute revascularization (TICI: Thrombolysis in Cerebral Infarction 2b + 3). Changes of the neurological status were precisely assessed by using the National Institutes of Health Stroke Scale (NIHSS). Ischemic lesions were scored by MRI with diffusion-weighted imaging (DWI), and blood flow in the middle cerebral artery territory was assessed by MRI with arterial spin labeling. Univariate analysis was performed to investigate correlations between hyperperfusion and demographic factors or the functional prognosis. RESULTS: Thirteen of the 27 (48%) patients developed hyperperfusion after reperfusion. A significant correlation was seen between hyperperfusion and the improvement of NIHSS at 24 hours (P < .0001), the duration of disturbance of consciousness (days) (P < .0001), DWI-ASPECTS (P = .001), hemorrhagic transformation (P = .007), and mRS less than or equal to 2 at 90 days (P = .007). CONCLUSIONS: The present findings suggested that some patients with AIS will develop hyperperfusion after successful acute revascularization. The status of hyperperfusion could prolong conscious disturbance and affect outcomes. Since the mechanism of hyperperfusion after revascularization depends on stroke etiology, diagnosing the type of ischemic stroke in the acute stage is important for managing postoperative treatment.

Decreased Antiatherogenic Protein Levels are Associated with Aneurysm Structure Alterations in MR Vessel Wall Imaging.

OBJECTIVE: Thickened intracranial aneurysm wall with atherosclerotic remodeling is a part of its degenerative scenario. Current magnetic resonance (MR)-vessel wall imaging enables the detection of atherosclerotic wall thickening as aneurysm wall enhancement. The purpose of this study was to examine the correlation between identified atherosclerotic remodeling in vessel wall imaging, and systemic atherosclerosis-related risk factors. METHODS: A total of 39 aneurysms in 38 consecutive patients scheduled to undergo microsurgical clipping or endovascular coiling of intracranial aneurysms were prospectively evaluated. All patients underwent aneurysm MR-vessel wall imaging and the presence of aneurysm wall enhancement on contrast-enhanced vessel wall imaging was evaluated. The relationship between aneurysm wall enhancement and patient demographic data, aneurysm morphology and atherosclerosis-related risk factors including blood laboratory data were assessed. RESULTS: Aneurysm wall enhancement was detected in 19 of 39 intracranial aneurysms (48.7%). The maximum diameter of the intracranial aneurysm (P < .01), apolipoprotein A2 (P < .01) and apolipoprotein C2 (P = .01) was significantly associated with the presence of aneurysm wall enhancement. In multivariate logistic regression analyses, the maximum diameter of the intracranial aneurysm (odds ratio: 1.67, 95% confidence interval: 1.17-3.05) and decreased apolipoprotein A2 (odds ratio: 0.62, 95% confidence interval: 0.34-0.97) was significantly correlated with aneurysm wall enhancement. CONCLUSIONS: Rather than atherosclerotic factors, antiatherogenic proteins reduction was associated with aneurysm wall enhancement in vessel wall imaging. To elucidate antiatherogenic factors might to help find out promoting factor of unruptured intracranial aneurysms instability.

[Weekly Vinblastine in Pediatric Optic Pathway/Hypothalamic Glioma:2 Cases Report].

It is reported that vinblastine monotherapy has promising activity in patients with pediatric optic pathway/hypothalamic glioma(OPHG)who experienced treatment failure after initial treatment with standard chemotherapy. However, there have been no reports on vinblastine monotherapy against OPHG in Japan. Since vinblastine is an unauthorized drug under the Ministry of Health and Welfare, we used it after completing an in-hospital institutional review board application for each case. In the first case, a 6-year-old boy with recurrent OPHG with hydrocephalus was referred to our hospital. Weekly vinblastine was started at a dose of 6mg/m2 and was then reduced to 5mg/m2 and 4mg/m2 sequentially due to hematotoxicity. After 11 cycles of vinblastine, improvement in hydrocephalus was observed. After 22 cycles of vinblastine, the best response was observed, and we continued treatment up to 35 cycles. Progression of the disease was observed after 47 cycles and then we changed treatment to another regimen after 48 cycles of vinblastine. In the second case, a 6-year-old boy with chemotherapy-naïve recurrent OPHG underwent chemotherapy with vincristine and carboplatin. After 9 treatment cycles with carboplatin, hypersensitivity was observed. Subsequently, he was treated using weekly vinblastine as per the same protocol as that in our first case. A moderate response was observed after 18 cycles of vinblastine. After 48 cycles of vinblastine, the best response was observed, and we completed treatment. In both cases, severe adverse events were not observed and the treatment was well-tolerated. Vinblastine administered once per week is well-tolerated and maintains quality of life in children with OPHG.