Ulceration location is associated with clinical course in carotid stenosis.

OBJECTIVE: Plaque ulceration in carotid artery stenosis is a risk factor for cerebral ischemic events; however, the characteristics that determine plaque vulnerability are not fully understood. We thus assessed the association between plaque ulceration sites and cerebrovascular ischemic attack. METHODS: We retrospectively collected the clinical data of 72 consecutive patients diagnosed with carotid artery stenosis with plaque ulcers. After excluding patients with pseudo-occlusion, a history of previous carotid endarterectomy or carotid artery stenting before the ulcer was first discovered, follow-up data of less than 1 month, or carotid endarterectomy or carotid artery stenting performed within 1 month after the ulcer was first discovered, 60 patients were ultimately included. Patients were divided into proximal and distal groups based on the ulcer location relative to the most stenotic point. The primary endpoints were ipsilateral cerebrovascular ischemic events ("ischemic events"), such as amaurosis fugax, transient ischemic attack, or ischemic stroke due to carotid artery stenosis with plaque ulceration. The association between ulcer location and ischemic events was also assessed. RESULTS: In the patients with plaque ulcer, more patients had proximal than distal plaque ulcers (39 vs 21; P = .028). The median follow-up duration was 3.8 years (interquartile range, 1.5-6.2 years). Nineteen patients (32%) experienced ischemic event. Ischemic events occurred more frequently in the distal than in the proximal group (18% vs 59%; P = .005). Kaplan-Meier curves demonstrated a significantly shorter event-free time in the distal group (log-rank P = .021). In univariate analysis, distal ulcer location was associated with ischemic events (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.13-7.65; P = .03). Multivariate analysis using two different models also showed that distal ulcer location was independently associated with ischemic events (Model 1: OR, 3.85; 95% CI, 1.26-11.78; P = .03; Model 2: OR, 4.31; 95% CI, 1.49-12.49; P = .009). CONCLUSIONS: Patients with carotid artery stenosis and plaque ulcers located distal to the most stenotic point are more likely to experience cerebrovascular ischemic attacks. Therefore, carotid plaques with ulcers located distal to the most stenotic point may be a potential indication for surgical treatment.

Irreversible postoperative cognitive impairment after unruptured intracranial aneurysm treatment in the elderly.

PURPOSE: Postoperative cognitive dysfunction and recovery remain unclear in older patients undergoing interventional therapies for unruptured intracranial aneurysms (UIAs). This study aimed to compare changes in postoperative cognitive function between younger and older patients and to detect factors associated with non-recovery from postoperative cognitive dysfunction. METHODS: This study reviewed 59 consecutive patients with UIAs who underwent interventional therapies, including microsurgical clipping or endovascular treatment, from 2021 to 2022. All patients were divided into the older (aged ≥ 70 years) and younger (aged < 70 years) groups. Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) were performed within 2 months before interventions, at 1 week postoperatively (POW1), and 3-6 months postoperatively (POM3-6). RESULTS: MMSE and FAB scores decreased more frequently in the older group than in the younger group at POW1 (older vs. younger: MMSE: 48% vs. 21%, p < 0.05; FAB: 56% vs. 18%, p < 0.01). In the older group, the FAB Z-score decreased in POW1 and recovered by POM3-6 (p < 0.01), while the MMSE Z-score continued to decrease (p = 0.04). Age and the preoperative MSME Z-score were significantly associated with non-recovery from decreased MMSE score at POM3-6 (recovery vs. non-recovery, age: 62 years old vs. 72 years old, p = 0.03, preoperative MMSE Z-score: 0.16 vs. - 0.90, p < 0.01). CONCLUSIONS: This retrospective study found that older patients were more likely to have a postoperative cognitive decline after UIA treatment and implicated that global cognitive function tended to decline more than executive function in the long term. In addition, this study demonstrated that lower preoperative cognitive function was associated with inadequate postoperative cognitive recovery. The findings potentially contribute to the establishment of indications for treating UIAs in older patients.

Pathological changes in the lenticulostriate artery indicate the mechanisms leading to intracranial hemorrhage in Moyamoya disease: a case report.

This case report details the pathological findings of a vessel wall identified as the bleeding point for intracranial hemorrhage associated with Moyamoya disease. A 29-year-old woman experienced intracranial hemorrhage unrelated to hyperperfusion following superficial temporal artery-middle cerebral artery bypass surgery. A pseudoaneurysm on the lenticulostriate artery (LSA) was identified as the causative vessel and subsequently excised. Examination of the excised pseudoaneurysm revealed a fragment of the LSA, with a disrupted internal elastic lamina and media degeneration. These pathological findings in a perforating artery, akin to the circle of Willis, provide insights into the underlying mechanisms of hemorrhage in Moyamoya disease.

[Japanese National Plan for Promotion of Measures against Stroke and Cardiovascular Diseases and Data-Based Health Management Initiatives].

This review outlines the recent advances in stroke and cardiovascular diseases control and direction of national data health reform. Since the enactment of the Basic Act on Countermeasures against Cardiovascular Diseases, the national government and related academic societies have collaborated to promote countermeasures based on five key pillars; medical systems development, registration projects promotion, human resource development, public awareness, and research promotion. Simultaneously, the government is intensively promoting data health reform to compensate for the delay in digital medicine that became evident in the new coronary infection. Data health reform has four major pillars; promotion of using genomic medicine and artificial intelligence(AI), promotion of personal health records(PHR), promotion of information utilization in medical and nursing care settings, and promotion of effective database utilization. Five years have passed since the Basic Act on Countermeasures for Cardiovascular Diseases was enacted, and it is important that the Japanese Stroke Association, Japanese Cardiovascular Society and other related academic societies, government, prefectures, and National Cardiovascular Center collaborate to vigorously promote the cardiovascular disease countermeasures.

Impact of tailored multimodal treatment for unruptured brain arteriovenous malformation: comparison with a randomized trial of unruptured brain arteriovenous malformations.

PURPOSE: The first randomized controlled study on unruptured brain arteriovenous malformations (bAVM), the ARUBA trial, demonstrate the superiority of medical management; however, it failed to completely rule out the efficacy of therapeutic interventions due to several limitations. This study aimed to examine the outcomes of multimodal interventional treatment for bAVM in terms of safety and efficacy. METHODS: We reviewed 226 consecutive patients with unruptured bAVM admitted to our institute between 2002 and 2022. Treatment methods were divided into medical management and therapeutic intervention, including microsurgery, stereotactic surgery, and endovascular intervention. First, the choice of therapeutic modalities was assessed in the pre-ARUBA (before February 2014) and post-ARUBA (after March 2014) eras. Second, the incidence of symptomatic stroke or death and functional prognosis with a modified Rankin scale (mRS) score of ≥2 at 5 years was compared between the medical management and therapeutic intervention. RESULTS: In the pre- and post-ARUBA groups, 73% and 84% of patients underwent therapeutic interventions, respectively (p = 0.053). The rate of symptomatic stroke or death was lower in patients who underwent interventional therapies than in those who underwent medical management (9.7% vs. 22%, p = 0.022); however, the opposite was observed in the ARUBA trial (31% vs. 10%). The annual incidence of stroke or death was also lower in the interventional therapy group (4.3%/y vs. 1.8%/year, hazard ratio = 0.45, 95% confidence interval: 0.18-1.08, p = 0.032). The rate of mRS score of ≥2 after a 5-year follow-up was 18% and 6% in the medical treatment and intervention groups (p = 0.14). CONCLUSIONS: The therapeutic intervention rate did not decrease, even after the publication of the ARUBA trial. The rate of stroke or death was lower in the intervention group, indicating that a tailored choice of multimodality is safe and effective for managing unruptured bAVM.

[Changes in Gamma Knife Radiosurgery(GKRS)in Patients with Metastatic Brain Tumors before and after COVID-19].

The spread of coronavirus disease 2019(COVID-19)is a concern as it may delay the detection of malignant tumors due to delayed medical checkups. We examined changes in the treatment of metastatic brain tumors before and after COVID- 19. A retrospective review of 211 patients with metastatic brain tumors who underwent initial gamma knife radiosurgery between July 2019 and December 2021 was conducted. Data collected include patient age, gender, the Karnofsky performance status(KPS), primary tumor control, number, total volume, and outcome during the COVID-19 emergency declaration period and outside of it. The patient number was 164 outside of the emergency period and 47 during the period. Symptomatic cases(KPS<90)and poor control of the primary site increased during the COVID-19 period. The treatment number and volume of brain metastasis did not change. Metastatic control after 4 months of treatment also showed no difference. The number of symptomatic patients increased during the emergency declaration period, suggesting that COVID- 19 may have reduced the rate of asymptomatic patients being seen. However, these were not enough to affect the prognosis at 4 months. Overall, the COVID-19 pandemic had a small impact on the provision of stereotactic radiotherapy for metastatic brain tumors.

Associations Between Adherence to Evidence-Based, Stroke Quality Indicators and Outcomes of Acute Reperfusion Therapy.

BACKGROUND: Quality indicators (QIs) are an accepted tool for measuring a hospital's performance in routine care. We examined national trends in adherence to the QIs developed by the Close The Gap-Stroke program by combining data from the health insurance claims database and electronic medical records, and the association between adherence to these QIs and early outcomes in patients with acute ischemic stroke in Japan. METHODS: In the present study, patients with acute ischemic stroke who received acute reperfusion therapy in 351 Close The Gap-Stroke-participating hospitals were analyzed retrospectively. The primary outcomes were changes in trends for adherence to the defined QIs by difference-in-difference analysis and the effects of adherence to distinct QIs on in-hospital outcomes at the individual level. A mixed logistic regression model was adjusted for patient and hospital characteristics (eg, age, sex, number of beds) and hospital units as random effects. RESULTS: Between 2013 and 2017, 21 651 patients (median age, 77 years; 43.0% female) were assessed. Of the 25 defined measures, marked and sustainable improvement in the adherence rates was observed for door-to-needle time, door-to-puncture time, proper use of endovascular thrombectomy, and successful revascularization. The in-hospital mortality rate was 11.6%. Adherence to 14 QIs lowered the odds of in-hospital mortality (odds ratio [95% CI], door-to-needle <60 min, 0.80 [0.69-0.93], door-to-puncture <90 min, 0.80 [0.67-0.96], successful revascularization, 0.40 [0.34-0.48]), and adherence to 11 QIs increased the odds of functional independence (modified Rankin Scale score 0-2) at discharge. CONCLUSIONS: We demonstrated national marked and sustainable improvement in adherence to door-to-needle time, door-to-puncture time, and successful reperfusion from 2013 to 2017 in Japan in patients with acute ischemic stroke. Adhering to the key QIs substantially affected in-hospital outcomes, underlining the importance of monitoring the quality of care using evidence-based QIs and the nationwide Close The Gap-Stroke program.

Joint effect of cognitive decline and walking ability on incidence of wandering behavior in older adults with dementia: A cohort study.

OBJECTIVES: Wandering behavior is one of the most troublesome behavioral disturbances in dementia. Inconsistent associations between physical function and wandering behavior were reported, and the effect of cognitive decline may be different according to walking ability. The purposes of this study are to investigate whether high walking ability is a risk factor for wandering behavior and to investigate the interaction of walking ability and cognitive function with wandering behavior in older adults with dementia. METHODS: This retrospective cohort study included 3979 elderly adults with dementia. The association of cognitive function and walking ability with incidence of wandering behavior during a 5-year follow-up period were examined using a generalized linear model, and relative excess risk due to interaction (RERI) was calculated. RESULTS: Severe cognitive decline and high walking ability were associated with a higher risk for wandering behavior. Additionally, some joint effects of cognitive decline and walking ability decline were higher than the sum of its individual effects (RERI [95% confidence interval], severe cognitive decline × 'walk with help': 1.58 [0.35, 2.81]; severe cognitive decline × 'independent': 3.09 [1.05, 5.14]). CONCLUSIONS: Effects of cognitive decline and walking ability on incidence of wandering behavior were observed, and the effects varied depending on their combination.

Molecular diagnosis of diffuse glioma using a chip-based digital PCR system to analyze IDH, TERT, and H3 mutations in the cerebrospinal fluid.

PURPOSE: Conventional genetic analyzers require surgically obtained tumor tissues to confirm the molecular diagnosis of diffuse glioma. Recent technical breakthroughs have enabled increased utilization of cell-free tumor DNA (ctDNA) in body fluids as a reliable resource for molecular diagnosis in various cancers. Here, we tested the application of a chip-based digital PCR system for the less invasive diagnosis (i.e., liquid biopsy) of diffuse glioma using the cerebrospinal fluid (CSF). METHODS: CSF samples from 34 patients with diffuse glioma were collected from the surgical field during craniotomy. Preoperative lumbar CSF collection was also performed in 11 patients. Extracted ctDNA was used to analyze diagnostic point mutations in IDH1 R132H, TERT promoter (C228T and C250T), and H3F3A (K27M) on the QuantStudio® 3D Digital PCR System. These results were compared with their corresponding tumor DNA samples. RESULTS: We detected either of the diagnostic mutations in tumor DNA samples from 28 of 34 patients. Among them, we achieved precise molecular diagnoses using intracranial CSF in 20 (71%). Univariate analyses revealed that the World Health Organization (WHO) grade (p = 0.0034), radiographic enhancement (p = 0.0006), and Mib1 index (p = 0.01) were significant predictors of precise CSF-based molecular diagnosis. We precisely diagnosed WHO grade III or IV diffuse gliomas using lumbar CSF obtained from 6 (87%) of 7 patients with tumors harboring any mutation. CONCLUSION: We established a novel, non-invasive molecular diagnostic method using a chip-based digital PCR system targeting ctDNA derived from CSF with high sensitivity and specificity, especially for high-grade gliomas.

Diagnostic accuracy for the epileptogenic zone detection in focal epilepsy could be higher in FDG-PET/MRI than in FDG-PET/CT.

OBJECTIVES: To examine the utility of FDG-PET/MRI in patients with epilepsy by comparing the diagnostic accuracy of PET/MRI and PET/CT in epileptogenic zone (EZ) detection. METHODS: This prospective study included 31 patients (17 males, 14 females) who underwent surgical resection for EZ. All patients were first scanned using FDG-PET/CT followed immediately with FDG-PET/MRI. Two series of PET plus standalone MR images were interpreted independently by five board-certified radiologists. A 4-point visual score was used to assess image quality. Sensitivities and visual scores from both PETs and standalone MRI were compared using the McNemar test with Bonferroni correction and Dunn's multiple comparisons test. RESULTS: The EZs were confirmed histopathologically via resection as hippocampal sclerosis (n = 11, 35.5%), gliosis (n = 8, 25.8%), focal cortical dysplasia (n = 6, 19.4%), and brain tumours (n = 6, 19.4%) including cavernous haemangioma (n = 3), dysembryoplastic neuroepithelial tumour (n = 1), ganglioglioma (n = 1), and polymorphous low-grade neuroepithelial tumour of the young (n = 1). The sensitivity of FDG-PET/MRI was significantly higher than that of FDG-PET/CT and standalone MRI (FDG-PET/MRI vs. FDG-PET/CT vs. standalone MRI; 77.4-90.3% vs. 58.1-64.5% vs. 45.2-80.6%, p < 0.0001, respectively). The visual scores derived from FDG-PET/MRI were significantly higher than those of FDG-PET/CT, as well as standalone MRI (2.8 ± 1.2 vs. 2.0 ± 1.1 vs. 2.1 ± 1.2, p < 0.0001, respectively). Compared to FDG-PET/CT, FDG-PET/MRI increased the visual score (51.9%, increased visual scores of 2 and 3). CONCLUSIONS: The diagnostic accuracy for the EZ detection in focal epilepsy could be higher in FDG-PET/MRI than in FDG-PET/CT. KEY POINTS: • Sensitivity of FDG-PET/MRI was significantly higher than that of FDG-PET/CT and standalone MRI (FDG-PET/MRI vs. FDG-PET/CT vs. standalone MRI; 77.4-90.3% vs. 58.1-64.5% vs. 45.2-80.6%, p < 0.0001, respectively). • Visual scores derived from FDG-PET/MRI were significantly higher than those of FDG-PET/CT and standalone MRI (2.8 ± 1.2 vs. 2.0 ± 1.1 vs. 2.1 ± 1.2, p < 0.0001, respectively). • Compared to FDG-PET/CT, FDG-PET/MRI increased the visual score (51.9%, increased visual scores of 2 and 3).

A Novel Hyperspectral Imaging System for Intraoperative Prediction of Cerebral Hyperperfusion Syndrome after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis in Patients with Moyamoya Disease.

BACKGROUND: Postoperative cerebral hyperperfusion syndrome (CHS) may occur after superficial temporal artery (STA)-middle cerebral artery (MCA) bypass for moyamoya disease (MMD). Predicting postoperative CHS is challenging; however, we previously reported the feasibility of using a hyperspectral camera (HSC) for monitoring intraoperative changes in brain surface hemodynamics during STA-MCA bypass. OBJECTIVE: To investigate the utility of HSC to predict postoperative CHS during STA-MCA bypass for patients with MMD. METHODS: Hyperspectral images of the cerebral cortex of 29 patients with MMD who underwent STA-MCA bypass were acquired by using an HSC before and after anastomosis. We then analyzed the changes in oxygen saturation after anastomosis and assessed its correlation with CHS. RESULTS: Five patients experienced transient neurological deterioration several days after surgery. 123I-N-Isopropyl-iodoamphetamine single-photon emission computed tomography scan results revealed an intense, focal increase in cerebral blood flow at the site of anastomosis without any cerebral infarction. Patients with CHS showed significantly increased oxygen saturation (SO2) in the cerebral cortex after anastomosis relative to those without CHS (33 ± 28 vs. 8 ± 14%, p < 0.0001). Receiver operating characteristic analysis results show that postoperative CHS likely occurs when the increase rate of cortical SO2 value is >15% (sensitivity, 85.0%; specificity, 81.3%; area under curve, 0.871). CONCLUSIONS: This study indicates that hyperspectral imaging of the cerebral cortex may be used to predict postoperative CHS in patients with MMD undergoing STA-MCA bypass.

Impact of Physician Volume and Specialty on In-Hospital Mortality of Ischemic and Hemorrhagic Stroke.

BACKGROUND: The degree of association between mortality and case volume/physician volume is well known for many surgical procedures and medical conditions. However, the link between physician volume and death rate in patients hospitalized for stroke remains unclear. This study analyzed the correlation between in-hospital stroke mortality and physician volume per hospital, considering board certification status.Methods and Results:For this retrospective registry-based cohort study, data were obtained from the Japanese nationwide registry on patients hospitalized for ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) between 2010 and 2016. The number of stroke care physicians and relevant board-certified physicians was also obtained. Odd ratios (ORs) of 30-day in-hospital mortality were estimated after adjusting for institutional and patient differences using generalized mixed logistic regression. From 295,150 (ischemic stroke), 98,657 (ICH), and 36,174 (SAH) patients, 30-day in-hospital mortality rates were 4.4%, 16.0%, and 26.6%, respectively. There was a correlation between case volume and physician volume. A higher number of stroke care physicians was associated with a reduction in 30-day mortality after adjusting for stroke case volume and comorbidities for all stroke types (all P for trend<0.05). CONCLUSIONS: An increased number of stroke care physicians was associated with reduced in-hospital mortality for all types of stroke. The volume threshold of board-certified physicians depends on the specialty and stroke type.

Measuring Quality of Care for Ischemic Stroke Treated With Acute Reperfusion Therapy in Japan　- The Close The Gap-Stroke.

BACKGROUND: In Japan there is no consensus on how to efficiently measure quality indicators (QIs), defined as a standard of care, for acute ischemic stroke (AIS). Using information from a health insurance claims database and electronic medical records, we evaluated the feasibility and validity of measuring QIs for AIS patients who received intravenous recombinant tissue plasminogen activator (IV rt-PA) or endovascular therapy (EVT).Methods and Results:AIS patients receiving rt-PA or EVT between 2013 and 2015 were identified. We selected 17 AIS QI measures for primary stroke centers (PSCs) and 8 for comprehensive stroke centers (CSCs). Defined QIs were calculated for each hospital and then averaged. In total, the data of 8,206 patients (rt-PA 83.7%, EVT 34.9%) from 172 hospitals were obtained. Median National Institute of Health Stroke Scale score at admission was 14, and 37.7% of the patients were functionally independent at discharge. All target QIs were successfully measured with fewer missing values, and the accuracy of preset data was about 90%. Adherence rates were low (<50%) in 5 QI measures among PSCs, including door-to-needle time ≤1 h, and in 1 QI measure among CSCs (door-to-brain and vascular imaging time ≤30 min). CONCLUSIONS: Measuring QIs for AIS by this novel approach was feasible and reliable in the provision of a national benchmark.

Mesenchymal glioblastoma-induced mature de-novo vessel formation of vascular endothelial cells in a microfluidic device.

High vascularization is a biological characteristic of glioblastoma (GBM); however, an in-vitro experimental model to verify the mechanism and physiological role of vasculogenesis in GBM is not well-established. Recently, we established a self-organizing vasculogenic model using human umbilical vein endothelial cells (HUVECs) co-cultivated with human lung fibroblasts (hLFs). Here, we exploited this system to establish a realistic model of vasculogenesis in GBM. We developed two polydimethylsiloxane (PDMS) devices, a doughnut-hole dish and a 5-lane microfluidic device to observe the contact-independent effects of glioblastoma cells on HUVECs. We tested five patient-derived and five widely used GBM cell lines. Confocal fluorescence microscopy was used to observe the morphological changes in Red Fluorescent Protein (RFP)-HUVECs and fluorescein isothiocyanate (FITC)-dextran perfusion. The genetic and expression properties of GBM cell lines were analyzed. The doughnut-hole dish assay revealed KNS1451 as the only cells to induce HUVEC transformation to vessel-like structures, similar to hLFs. The 5-lane device assay demonstrated that KNS1451 promoted the formation of a vascular network that was fully perfused, revealing the functioning luminal construction. Microarray analysis revealed that KNS1451 is a mesenchymal subtype of GBM. Using a patient-derived mesenchymal GBM cell line, mature de-novo vessel formation could be induced in HUVECs by contact-independent co-culture with GBM in a microfluidic device. These results support the development of a novel in vitro research model and provide novel insights in the neovasculogenic mechanism of GBM and may potentially facilitate the future detection of unknown molecular targets.

Current trend in treatment of glioblastoma in Japan: a national survey using the diagnostic procedure combination database (J-ASPECT study-glioblastoma).

BACKGROUND: In the treatment for glioblastoma (GBM), treatment modalities, such as bevacizumab (BEV) and carmustine wafers implants have been approved in Japan since 2013. However, it is unclear whether such a trend in treatment complexity can accelerate treatment centralization. The aim of this study was to reveal the current trend in the treatment of GBM in Japan. METHODS: We used diagnostic procedure combination (DPC) database to analyze the data of 1,774 patients from 305 institutions between April 2016 and March 2019. To analyze the situations associated with first-line BEV use during concurrent TMZ (temozolomide)-radiotherapy, we compared TMZ alone and TMZ-BEV groups. RESULTS: Of the 1,774 patients with GBM, tumor removal by craniotomy was performed in 1,572 (88.6%) patients, and stereotactic biopsy was performed in 156 (8.8%) patients. A total of 1,229 (69.3%) patients underwent radiotherapy, and 1,287 (72.5%) patients underwent chemotherapy. TMZ alone was administered to 878 (68.2%) and TMZ combined with BEV in 381 (29.6%) patients. In the TMZ-BEV group, as compared to the TMZ-alone group, the rate of discharge to home was significantly lower (P = 0.0044), and the rate of stereotactic biopsy was significantly higher (P < 0.0001). No significant difference was observed in the distribution of patients between the TMZ alone and TMZ-BEV groups depending on the scale of institution (P = 0.1240). CONCLUSION: First-line BEV administration seems to be selected properly regardless of the institutional scale. This Japan-wide study of GBM treatment revealed that high level and newly introduced treatments have been steadily generalized in Japanese institutions.

AI-Assisted In-House Power Monitoring for the Detection of Cognitive Impairment in Older Adults.

In-home monitoring systems have been used to detect cognitive decline in older adults by allowing continuous monitoring of routine activities. In this study, we investigated whether unobtrusive in-house power monitoring technologies could be used to predict cognitive impairment. A total of 94 older adults aged ≥65 years were enrolled in this study. Generalized linear mixed models with subject-specific random intercepts were used to evaluate differences in the usage time of home appliances between people with and without cognitive impairment. Three independent power monitoring parameters representing activity behavior were found to be associated with cognitive impairment. Representative values of mean differences between those with cognitive impairment relative to those without were -13.5 min for induction heating in the spring, -1.80 min for microwave oven in the winter, and -0.82 h for air conditioner in the winter. We developed two prediction models for cognitive impairment, one with power monitoring data and the other without, and found that the former had better predictive ability (accuracy, 0.82; sensitivity, 0.48; specificity, 0.96) compared to the latter (accuracy, 0.76; sensitivity, 0.30; specificity, 0.95). In summary, in-house power monitoring technologies can be used to detect cognitive impairment.

First-line bevacizumab contributes to survival improvement in glioblastoma patients complementary to temozolomide.

INTRODUCTION: First-line bevacizumab (BEV) is now available as a treatment option for glioblastoma patients with severe clinical conditions in Japan. However, the survival benefits remain controversial. To elucidate these potential survival benefits, we retrospectively analyzed survival in glioblastoma patients receiving BEV. METHODS: We analyzed survival in 120 patients with IDH-wild type glioblastoma treated from 2002 to 2018. Overall survival (OS) was assessed in three treatment era subgroups [pre-temozolomide (TMZ), TMZ, and TMZ-BEV], and the correlations of prognostic factors with survival were evaluated. RESULTS: An improvement in survival was observed after BEV approval (median OS in the pre-TMZ, TMZ, and TMZ-BEV eras: 14.6, 14.9, and 22.1 months, respectively). A Cox proportional hazards model identified extent of resection and MGMT methylation status as significant prognostic factors in the TMZ era; however, these factors were not significant in the TMZ-BEV era. In subgroup analyses, patients with MGMT methylation had improved OS after TMZ introduction (pre-TMZ vs. TMZ, 18.5 vs. 28.1 months; P = 0.13), and those without MGMT methylation had significantly increased OS after BEV approval (TMZ vs. TMZ-BEV, 12.2 vs. 16.7 months; P = 0.04). CONCLUSIONS: Our findings imply that optional first-line administration of BEV can overcome the impact of conventional risk factors and prolong survival complementary to TMZ. The patient subgroups benefitting from TMZ and BEV did not seem to overlap, and stratification based on risk factors, including MGMT methylation status, might be effective for selecting patients in whom BEV should be preferentially used as a first-line therapy.

Vessel-selective 4D-MR angiography using super-selective pseudo-continuous arterial spin labeling may be a useful tool for assessing brain AVM hemodynamics.

OBJECTIVES: To evaluate the usefulness of 4D-MR angiography based on super-selective pseudo-continuous ASL combined with keyhole and view-sharing (4D-S-PACK) for vessel-selective visualization and to examine the ability of this technique to visualize brain arteriovenous malformations (AVMs). METHODS: In this retrospective study, 15 patients (ten men and five women, mean age 44.0 ± 16.9 years) with brain AVMs were enrolled. All patients were imaged with 4D-PACK (non-selective), 4D-S-PACK, and digital subtraction angiography (DSA). Observers evaluated vessel selectivity, identification of feeding arteries and venous drainage patterns, visualization scores, and contrast-to-noise ratio (CNR) for each AVM component. Measurements were compared between the MR methods. RESULTS: Vessel selectivity was graded 4 in 43/45 (95.6%, observer 1) and 42/45 (93.3%, observer 2) territories and graded 3 in two (observer 1) and three (observer 2) territories. The sensitivity and specificity for identification of feeding arteries for both observers was 88.9% and 100% on 4D-PACK, and 100% and 100% on 4D-S-PACK, respectively. For venous drainage, the sensitivity and specificity was 100% on both methods for observer 1. The sensitivity and specificity for observer 2 was 94.4% and 83.3% on 4D-PACK, and 94.4% and 91.7% on 4D-S-PACK, respectively. The CNRs at the timepoint of 1600 ms were slightly lower in 4D-S-PACK than in 4D-PACK for all AVM components (Feeding artery, p = .02; nidus, p = .001; and draining artery, p = .02). The visualization scores for both observers were not significantly different between 4D-PACK and 4D-S-PACK for all components. CONCLUSIONS: 4D-S-PACK could be a useful non-invasive clinical tool for assessing hemodynamics in brain AVMs. KEY POINTS: • The 4D-MR angiography based on super-selective pseudo-continuous arterial spin labeling combined with CENTRA-keyhole and view-sharing (4D-S-PACK) enabled excellent vessel selectivity. • The 4D-S-PACK enabled the perfect identification of feeding arteries of brain arteriovenous malformation (AVM). • 4D-S-PACK could be a non-invasive clinical tool for assessing hemodynamics in brain AVMs.

Differentiation of high-grade from low-grade diffuse gliomas using diffusion-weighted imaging: a comparative study of mono-, bi-, and stretched-exponential diffusion models.

PURPOSE: Diffusion-weighted imaging (DWI) plays an important role in the preoperative assessment of gliomas; however, the diagnostic performance of histogram-derived parameters from mono-, bi-, and stretched-exponential DWI models in the grading of gliomas has not been fully investigated. Therefore, we compared these models' ability to differentiate between high-grade and low-grade gliomas. METHODS: This retrospective study included 22 patients with diffuse gliomas (age, 23-74 years; 12 males; 11 high-grade and 11 low-grade gliomas) who underwent preoperative 3 T-magnetic resonance imaging from October 2014 to August 2019. The apparent diffusion coefficient was calculated from the mono-exponential model. Using 13 b-values, the true-diffusion coefficient, pseudo-diffusion coefficient, and perfusion fraction were obtained from the bi-exponential model, and the distributed-diffusion coefficient and heterogeneity index were obtained from the stretched-exponential model. Region-of-interests were drawn on each imaging parameter map for subsequent histogram analyses. RESULTS: The skewness of the apparent diffusion, true-diffusion, and distributed-diffusion coefficients was significantly higher in high-grade than in low-grade gliomas (0.67 ± 0.67 vs. - 0.18 ± 0.63, 0.68 ± 0.74 vs. - 0.08 ± 0.66, 0.63 ± 0.72 vs. - 0.15 ± 0.73; P = 0.0066, 0.0192, and 0.0128, respectively). The 10th percentile of the heterogeneity index was significantly lower (0.77 ± 0.08 vs. 0.88 ± 0.04; P = 0.0004), and the 90th percentile of the perfusion fraction was significantly higher (12.64 ± 3.44 vs. 7.14 ± 1.70%: P < 0.0001), in high-grade than in low-grade gliomas. The combination of the 10th percentile of the true-diffusion coefficient and 90th percentile of the perfusion fraction showed the best area under the receiver operating characteristic curve (0.96). CONCLUSION: The bi-exponential model exhibited the best diagnostic performance for differentiating high-grade from low-grade gliomas.

A case of diffuse midline glioma, H3 K27M mutant mimicking a hemispheric malignant glioma in an elderly patient.

Diffuse midline glioma, H3 K27M mutant arises from midline structures of the central nervous system and predominately affects pediatric patients. However, this disease entity was only recently established, and the clinical phenotypic spectrum remains largely unclear. We herein report a rare case of diffuse midline glioma, H3 K27M mutant with an unusual distribution in an elderly woman who presented with a diffuse glioma that invaded both sides of the thalami, and left hippocampus and frontoparietal lobes, thus mimicking a hemispheric malignant glioma. A biopsy of the lobular lesion led to a molecular diagnostic confirmation of diffuse midline glioma, H3 K27M mutant. The patient received concurrent bevacizumab and temozolomide therapy with radiation therapy and survived for 30 months. This case highlights the possibility that a glioma with cerebral hemispheric spread in an elderly patient may harbor the H3 K27M mutation.