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Background and Objectives: Some reports suggest that older patients with traumatic brain injury (TBI) are more likely to experience acute intracranial hemorrhage, resulting in poor outcomes. However, the association between precise chronological age and use of antithrombotic agents with acute intracranial hemorrhage in these patients remains unknown. The aim of this study was to determine factors associated with acute intracranial hemorrhage and poor outcomes in patients with TBI, including chronological age and use of antithrombotic agents., Methods: Patients hospitalized for TBI between January 2006 and December 2021 were included. Patients were categorized by age groups of <65 years, 65 to 74 years, 75 to 84 years, and ≥85 years. Associations between each age group and acute intracranial hemorrhage, a poor outcome at discharge, and in-hospital mortality were evaluated., Results: The cohort included 1086 patients, with 713 (65.7%) in the ≥65 age group. Although chronological age was associated with acute intracranial hemorrhage in patients aged <65 years (odds ratio [OR] 1.02; 95% CI 1.01-1.03), it was not associated with patients aged ≥65 years. None of the antithrombotic agents investigated were associated with acute intracranial hemorrhage in the group aged ≥65 years. Although chronological age was associated with a poor outcome in patients aged <65 years (OR 1.03; 95% CI 1.01-1.07), it was not associated in those aged ≥65 years. The ≥85 year age group (OR 2.30; 95% CI 1.18-4.51) compared with <65 years were significantly associated with a poor outcome. None of the antithrombotic agents investigated were associated with a poor outcome in the group aged ≥65 years., Conclusion: Our findings confirmed the lack of an association of chronological age and antithrombotic agents with acute intracranial hemorrhage in the group of older adults with TBI. Our findings suggest that antithrombotic agents may be safely used, even in older adults., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Introduction: Cerebral small-vessel disease (CSVD) is a common cause of cognitive decline and stroke. Several studies have shown that smoking is a risk factor for CSVD progression. However, the extent to which smoking exacerbates CSVD lesions remains unclear. In this study, we aimed to clarify the association between total smoking exposure and the severity of CSVD in healthy participants., Methods: We analyzed the data of participants aged ≥50 years who underwent brain screening. The participants' age, sex, body mass index, alcohol consumption history, and medical history (hypertension, diabetes mellitus, and dyslipidemia) were investigated. Smoking status was assessed in pack-years, and smokers were classified as current or past smokers. CSVD findings on magnetic resonance imaging were used to evaluate the severity of periventricular hyperintensity (PVH), deep subcortical white matter hyperintensity (DSWMH), and enlarged perivascular spaces (EPVSs). The EPVSs were measured in the basal ganglia and centrum semiovale regions. Multivariable ordinal logistic regression analyses were performed to evaluate the effect of smoking, adjusted for the participants' baseline characteristics., Results: A total of 2,137 participants were included in this study. The mean age of the participants was 58.7 years. The mean pack-years were 20.5 for past smokers and 26.8 for current smokers. Among current smokers, increased pack-years were significantly associated with a high EPVS burden in the basal ganglia (odds ratio: 1.14, 95% confidence interval: 1.00-1.28), whereas no such significant association was found for past smokers. No statistically significant association was found between pack-years and the risks of PVH, DSWMH, or EPVS in the centrum semiovale., Conclusion: Current smoking was associated with a dose-dependent risk of EPVS in the basal ganglia in healthy participants., (© 2024 S. Karger AG, Basel.)

The incidence of subarachnoid hemorrhages (SAHs) in Japan has recently decreased. However, trends in the annual rates of unruptured cerebral aneurysms (UCAs) are unclear because calculations based on follow-up periods are limited to patients with ruptured cerebral aneurysms. We aimed to clarify current trends in the estimated annual rupture rates of UCAs in Japan and to identify the most relevant contributing factors. We analyzed data from the Japanese Ministry of Health, Labour and Welfare and records of the Japan Neurosurgical Society. The estimated annual rupture rates of UCAs between 2003 and 2018 were calculated according to age-adjusted mortality rates of SAH and number of treated ruptured cerebral aneurysms (RCAs). We estimated trends in annual rupture rates using sensitivity analysis and assessed associations between estimated annual rupture rates and the prevalences of hypertension and current smoking. The estimated annual rupture rate of UCAs significantly decreased from 1.44 to 0.87% and from 0.92 to 0.76%, respectively, in terms of age-adjusted mortality rates of SAH and number of treated RCAs (p < 0.001). The range of changes in estimated annual rupture rates of UCAs was - 1.13%‒0.83%, representing a declining UCA trend of 88%. The estimated annual rupture rates of UCAs declined by 0.02-0.10% and 0.01-0.05% with every percent decrease in hypertension and current smoking prevalence, respectively. The estimated annual rupture rate of UCAs has recently decreased in Japan, possibly due to a decrease in the prevalence of hypertension rather than smoking., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/Objective : No guidelines indicate surgical risk factors for the elderly because of the lack of data from general neurosurgeons. To better understand the management of surgical risk in elderly patients with meningiomas based on a national database in Japan. Methods : Results of surgically treated meningiomas were explored in 8138 patients registered in the Diagnosis Procedure Combination database in Japan during 2010-2015. Age (<65, 65-74, and ≥75 years), sex, Barthel index (BI), medical history, tumor location, oral medication prescriptions on admission, and stroke complications were evaluated. Multivariate logistic regression analysis identified risk factors for stroke complications, BI deterioration between admission and discharge, and in-hospital mortality. Results : Advanced age was the prominent risk factor for BI deterioration (odds ratio: 3.26; 95% confidence interval: 2.69-3.95) but not for in-hospital mortality. Lower BI (60-80) on admission increased the risk of BI deterioration in all age groups; however, BI < 60 demonstrated a significant inverse risk (0.47; 0.32-0.69) in the elderly (≥75 years). Location (falx, parasagittal, and deep) and anticoagulants were not significant risk factors for BI deterioration in patients aged ≥ 75 years, despite being significant risk factors in patients aged <65 and/or 65-74 years. Conclusions : Although advanced age could lead to postoperative functional decline at discharge, it was not sufficiently significant enough to be associated with in-hospital mortality. Because of the possibility of recovery even in elderly patients with severe disabilities, appropriate surgical selection and optimal management may lead to favorable functional outcomes in elderly patients with meningiomas.

We aimed to develop a new artificial intelligence software that can automatically extract and measure the volume of white matter hyperintensities (WMHs) in head magnetic resonance imaging (MRI) using only thick-slice fluid-attenuated inversion recovery (FLAIR) sequences from multiple centers. We enrolled 1092 participants in Japan, comprising the thick-slice Private Dataset. Based on 207 randomly selected participants, neuroradiologists annotated WMHs using predefined guidelines. The annotated images of participants were divided into training (n = 138) and test (n = 69) datasets. The WMH segmentation model comprised a U-Net ensemble and was trained using the Private Dataset. Two other models were trained for validation using either both thin- and thick-slice MRI datasets or the thin-slice dataset alone. The voxel-wise Dice similarity coefficient (DSC) was used as the evaluation metric. The model trained using only thick-slice MRI showed a DSC of 0.820 for the test dataset, which is comparable to the accuracy of human readers. The model trained with the additional thin-slice dataset showed only a slightly improved DSC of 0.822. This automatic WMH segmentation model comprising a U-Net ensemble trained on a thick-slice FLAIR MRI dataset is a promising new method. Despite some limitations, this model may be applicable in clinical practice., (© 2024. The Author(s).)

Neurosurgeons of the future must possess the ability to engage in preoperative simulation. However, given the changing medical practices and redistribution of tasks among physicians, the significance of radiological technologists is increasing. In this article, we describe the collaboration between radiological technologists and the hospital system to simplify preoperative simulation for young physicians. Preparation for preoperative simulation is a collaborative process with radiological technologists, aiming to facilitate mutual learning and risk management. It involves recognizing and utilizing the expertise of certified radiological technologists for imaging and additional surgical support, with due consideration given to the additional fees. The creation of an in-hospital arrangement system for preoperative simulation ensures more efficient and safer workflow.

Importance: Cell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow-derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke., Objective: To assess the efficacy and safety of MultiStem when administered within 18 to 36 hours of ischemic stroke onset., Design, Setting, and Participants: The Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized clinical trial was conducted at 44 academic and clinical centers in Japan between November 15, 2017, and March 29, 2022. Inclusion criteria were age 20 years or older, presence of acute ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 8-20 at baseline), confirmed acute infarction involving the cerebral cortex and measuring more than 2 cm on the major axis (determined with diffusion-weighted magnetic resonance imaging), and a modified Rankin Scale (mRS) score of 0 or 1 before stroke onset. Data analysis was performed between May 9 and August 15, 2022., Exposure: Patients were randomly assigned to either intravenous MultiStem in 1 single unit of 1.2 billion cells or intravenous placebo within 18 to 36 hours of ischemic stroke onset., Main Outcomes and Measures: The primary end points were safety and excellent outcome at day 90, measured as a composite of a modified Rankin Scale (mRS) score of 1 or less, a NIHSS score of 1 or less, and a Barthel index score of 95 or greater. The secondary end points were excellent outcome at day 365, mRS score distribution at days 90 and 365, and mRS score of 0 to 1 and 0 to 2 at day 90. Statistical analysis of efficacy was performed using the Cochran-Mantel-Haenszel test., Results: This study included 206 patients (104 received MultiStem and 102 received placebo). Their mean age was 76.5 (range, 35-95) years, and more than half of patients were men (112 [54.4%]). There were no between-group differences in primary and secondary end points. The proportion of excellent outcomes at day 90 did not differ significantly between the MultiStem and placebo groups (12 [11.5%] vs 10 [9.8%], P = .90; adjusted risk difference, 0.5% [95% CI, -7.3% to 8.3%]). The frequency of adverse events was similar between treatment groups., Conclusions and Relevance: In this randomized clinical trial, intravenous administration of allogeneic cell therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve short-term outcomes. Further research is needed to determine whether MultiStem therapy for ischemic stroke has a beneficial effect in patients who meet specific criteria, as indicated by the exploratory analyses in this study., Trial Registration: ClinicalTrials.gov Identifier: NCT02961504.

Background and Objectives: The differences in clinical outcomes between endovascular coiling (EC) and surgical clipping (SC) in patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) are controversial. Therefore, this study aimed to evaluate whether EC is superior to SC and identify risk factors in patients with poor-grade aSAH., Methods: We used data from the "Predict for Outcome Study of aneurysmal SubArachnoid Hemorrhage." World Federation of Neurological Societies (WFNS) grade III-V aSAH was defined as poor-grade aSAH, and unfavorable clinical outcomes (modified Rankin Scale scores 3-6) were compared between SC and EC after propensity score matching (PSM). In-hospital mortality was similarly evaluated. Predictors of unfavorable clinical outcomes were identified using multivariable analysis., Results: Ultimately, 1326 (SC: 847, EC: 479) and 632 (SC: 316, EC: 316) patients with poor-grade aSAH were included before and after PSM, respectively. Unfavorable clinical outcomes at discharge were significantly different between SC and EC before (72.0% vs 66.2%, P = .026) and after PSM (70.6% vs 63.3%, P = .025). In-hospital mortality was significantly different between groups before PSM (10.5% vs 16.1%, P = .003) but not after PSM (10.4% vs 12.7%, P = .384). Predictors of unfavorable clinical outcomes in both SC and EC were WFNS grade V, older than 70 years, and Fisher computed tomography (CT) grade 4. Predictors of unfavorable clinical outcomes only in SC were WFNS grade IV (odds ratio: 2.46, 95% CI: 1.22-4.97, P = .012) and Fisher CT grade 3 (4.90, 1.42-16.9, P = .012). Predictors of unfavorable clinical outcome only in EC were ages of 50s (3.35, 1.37-8.20, P = .008) and 60s (3.28, 1.43-7.52, P = .005)., Conclusion: EC resulted in significantly more favorable clinical outcomes than SC in patients with poor-grade aSAH, without clear differences in in-hospital mortality. The benefit of EC over SC might be particularly remarkable in patients with WFNS grade IV and Fisher CT grade 3., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

This study aims to evaluate the academic activities of female neurosurgeons at all branch meetings of the Japan Neurosurgical Society and identify related issues they encountered. The programs of all seven branch meetings of the Japan Neurosurgical Society (Hokkaido, Tohoku, Kanto, Chubu, Kinki, Chugoku/Shikoku, and Kyushu) were used to determine the number of presentations and chairpersons by sex. The covered period was from January 2008 to December 2020, which was available for viewing during the survey. Of note, only the Kinki branch used data from January 2008 to December 2019. The Neurologia Medico-chirurgica (NMC), the journal of the Japan Neurosurgical Society, was also reviewed to identify publication achievements during the same period. In all seven branches, the percentage of presentations given by female physicians increased from 7.9% in 2008 to 9.6% in 2020 (p < 0.05).Conversely, the percentage of female chairpersons in all branch meetings did not change over time and it was significantly lower (1.1%) than that of female presenters (7.9%) for all branch meetings combined in over 13 years (p < 0.01). In the NMC, the number of articles with female physicians as first authors did not increase or decrease over the years. We conclude that efforts to smoothly promote female neurosurgeons as chairpersons and increase the number of female first authors are necessary to facilitate their academic activities.

Diagnostic image analysis for unruptured cerebral aneurysms using artificial intelligence has a very high sensitivity. However, further improvement is needed because of a relatively high number of false positives. This study aimed to confirm the clinical utility of tuning an artificial intelligence algorithm for cerebral aneurysm diagnosis. We extracted 10,000 magnetic resonance imaging scans of participants who underwent brain screening using the "Brain Dock" system. The sensitivity and false positives/case for aneurysm detection were compared before and after tuning the algorithm. The initial diagnosis included only cases for which feedback to the algorithm was provided. In the primary analysis, the sensitivity of aneurysm diagnosis decreased from 96.5 to 90% and the false positives/case improved from 2.06 to 0.99 after tuning the algorithm (P < 0.001). In the secondary analysis, the sensitivity of aneurysm diagnosis decreased from 98.8 to 94.6% and the false positives/case improved from 1.99 to 1.03 after tuning the algorithm (P < 0.001). The false positives/case reduced without a significant decrease in sensitivity. Using large clinical datasets, we demonstrated that by tuning the algorithm, we could significantly reduce false positives with a minimal decline in sensitivity., (© 2023. The Author(s).)

Background: There is considerable debate regarding the definition of grade V subarachnoid hemorrhage (SAH). Recently, the Glasgow Coma Scale-Pupil (GCS-P) score was advocated for assessing traumatic brain injury., Objective: To study the significance of pupillary findings and GCS-P in the management and outcomes of the World Federation of Neurological Societies (WFNS) grade V SAH., Methods: We analyzed data obtained from a Japanese nationwide prospective registration study on the modified WFNS SAH grading system. Bilateral pupillary dilatation without reactivity was defined as pupil score 2, unilateral pupil dilation without reactivity as score 1, and no pupil dilatation with reactivity as score 0. The GCS-P score was calculated by subtracting the pupil score from the total GCS score. The characteristics and pupillary findings were examined in patients with each GCS score in WFNS grade V., Results: Among 1638 patients, 472 (men/women = 161/311, age 67.0 ± 14.0 years) had a GCS score of ≤6 after initial resuscitation on arrival. Overall, lower GCS scores were associated with poorer neurological outcomes and higher mortality. Aneurysms were treated in 20.5%, 53.9%, and 67.5% of patients with pupil scores of 2, 1, and 0, respectively. Favorable outcomes (modified Rankin Scale 0-2) at 3 months occurred in 4.5%, 10.8%, and 21.4% in patients with pupil scores 2, 1, and 0, respectively ( P < .0001), and in 0%, 0%, 13.6%, 28.6%, 16.7%, and 18.8% of patients with GCS-P scores 1 to 6 ( P < .0001), respectively., Conclusion: Our study confirmed the significance of pupillary findings in decision making and outcomes of WFNS grade V SAH., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Currarino syndrome is characterized by a triad of anorectal malformations, sacral defects, and presacral masses. Although it is not extremely rare, this report presents a surgical case of Currarino syndrome with syringomyelia and discusses related literature. The patient is a girl, aged 2 years and 2 months, who presented with marked constipation, chronic cystitis, and lower limb weakness. After examining the patient through magnetic resonance imaging, we diagnosed her with rectal compression due to meningocele and syringomyelia. The base of the meningocele was detached, and the spinal cord was untethered. One week after surgery, her lower limb weakness and constipation improved. Following up on symptoms and performing imaging is essential to determine a treatment plan for Currarino syndrome. (Received 28 February, 2023; Accepted 22 March, 2023; Published 1 August, 2023).

Objective: Cerebral infarction due to cerebral vasospasm (IVS) after aneurysmal subarachnoid hemorrhage is associated with poor outcomes and symptomatic cerebral vasospasm (SVS). However, the difference of risk factors between SVS and IVS was unclear to date. In this study, we aimed to elucidate the risk factors for SVS and IVS based on the registry study., Methods: The modified World Federation of Neurosurgical Societies scale study comprises 1863 cases. Patients with aneurysmal subarachnoid hemorrhage who underwent radical treatment within 72 hours with a premorbid modified Rankin Scale score 0-2 as the inclusion criteria were retrospectively examined. The risk factors for SVS and IVS were analyzed using multivariable logistic regression analysis., Results: Among them, 1090 patients who met the inclusion criteria were divided into 2 groups according to SVS and IVS; 273 (25%) patients with SVS and 92 (8.4%) with IVS. Age was not a risk factor for SVS, but for IVS, and Fisher scale was a risk factor for SVS, but not for IVS., Conclusions: The prevalence of IVS was not associated with the Fisher scale but with older age, suggesting possible factors other than SVS. Different associated factors between SVS and IVS were confirmed in this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Some aneurysmal subarachnoid hemorrhage (SAH) patients are delayed in their presentation. This can cause a washout of the subarachnoid hematoma and a potential misdiagnosis. As a result, they may suffer rerupture of the aneurysm and preventable deterioration. We investigated the factors that influence delayed SAH presentation., Methods: Aneurysmal SAH patients treated at 9 stroke centers from 2002 to 2020 were included. Age, gender, pre-SAH modified Rankin scale, World Federation of Neurological Surgeons grade, Fisher group, day of presentation, aneurysm treatment method, past history of cerebral stroke, comorbidity of hypertension and/or diabetes mellitus, and modified Rankin scaleat discharge were assessed retrospectively. We formed 2 groups based on the day of presentation after the onset of SAH: day 0-3 (early) and other (delayed). Logistic regression analyses detected the factors that influenced the day of presentation and outcome for SAH. A P- value <0.05 was considered significant., Results: Delayed presentation comprised 282 cases (6.3%) of 4507 included cases. Logistic regression analyses showed that patients in an urban area, of male gender, low WFNS grade and low Fisher group correlated significantly with a delayed presentation. But delayed presentation did not influence outcome at discharge., Conclusions: Area of residency and gender correlated with delayed presentation after SAH in Japan. Urbanization, male gender, and mild SAH lead patients to delay presentation. The factors underlying these tendencies will be analyzed in a future prospective study., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Although several studies have reported on the impact of the body mass index (BMI) on functional outcome of aneurysmal subarachnoid hemorrhage (aSAH), the relationship remains unclear. This study aimed to investigate the risk factors of poor outcome of aSAH, with particular attention to BMI. A total of 860 patients with aSAH were enrolled in our registry at Shimane Prefectural Central Hospital between 2000 and 2017, of whom 393 were included in the analysis. Basic patient characteristics, including BMI, and data related to aSAH were recorded. We conducted a univariable analysis, followed by a multivariable analysis to identify the risk factors of poor outcome, defined as a modified Rankin Scale score > 2 at discharge. We also compared our study with previous studies that reported a relationship between BMI and aSAH. Multivariable analysis revealed that age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.07-1.12), underweight (OR, 2.36; 95% CI, 1.13-4.90), overweight (OR, 2.22; 95% CI, 1.06-4.64), World Federation of Neurosurgical Societies grade (III vs I: OR, 3.10; 95% CI, 1.03-9.35; IV vs I: OR, 8.02; 95% CI, 3.54-18.19; V vs I: OR, 13.37; 95% CI, 5.33-33.54), and symptomatic vasospasm (OR, 3.40; 95% CI, 1.73-6.70) were risk factors for poor outcome at discharge. This study showed the association of underweight (BMI < 18.5 kg/m 2 ) and overweight (≥ 25 kg/m 2 ) with poor outcome; therefore, both high and low BMI are associated with a poor outcome at discharge for patients with aSAH. Clinical trial registry: University Hospital Medical Information Network (UMIN000035160; date of registration: December 6, 2018)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although chronological age is associated with mortality and morbidity after surgery for unruptured cerebral aneurysms (UCAs), there is little evidence regarding an association between the simplified 5-factor modified frailty index (mFI-5) and postoperative outcomes based on age group., Objective: To investigate the association of the mFI-5 score with worse outcomes, mortality, and complications in patients after surgery for UCA by chronological age groups using a Japanese national database., Methods: This study included 32 902 patients with UCAs enrolled in a Japanese national database between 2011 and 2015. Age group (younger than 65 years, 65-74 years, and 75 years or older), sex, UCA location, treatment, medications, Barthel Index (BI), medical history, mFI-5 score, and in-hospital mortality and complications were evaluated. We identified risk factors for worsening BI score, in-hospital mortality, and overall postoperative complications in each age group., Results: In total, 14 465 patients were enrolled in this study. Multivariable analysis showed that elderly groups and patients with an mFI-5 score ≥2 items were associated with worsening BI scores (odds ratio 1.95; 95% CI 1.52-2.51) and in-hospital complications (odds ratio 1.79; CI 1.49-2.15), despite having no association with in-hospital mortality. Multivariable analysis by age groups showed that the mFI-5 score ≥2 items was associated with in-hospital complications in all age groups, unlike chronological age in patients younger than 74 years., Conclusion: The mFI-5 score was a more useful associated factor of in-hospital complications than chronological age in patients younger than 74 years undergoing surgery for UCA., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Background: The perioperative risk of sporadic hemangioblastomas (HBs) and von Hippel-Lindau disease (VHL)-associated hemangioblastomas (VHL-associated HBs) remains unclear due to the rare prevalence of HB. Therefore, this study aimed to clarify risk factors for better surgical management of patients with HBs., Methods: A retrospective analysis of surgically treated HB patients registered in the Diagnosis Procedure Combination database of Japan, between 2010 and 2015, was performed. Age, sex, sporadic HBs or VHL-associated HBs, medical history, tumor location, hospital case load, postoperative complications, and Barthel index (BI) deterioration were assessed. We also evaluated the outcomes and factors of perioperative BI deterioration., Results: In total, 676 patients with 609 intracranial lesions, 64 spinal lesions, and 3 with both types were eligible. Among them, 618 and 58 patients had sporadic HBs and VHL-associated HBs, respectively. The rates of perioperative BI deterioration were 12.5% and 12.2% for sporadic HBs and VHL-associated HBs, respectively. Perioperative mortality was 1.8% and 0% for sporadic HBs and VHL-associated HBs, respectively. Male sex, old age, high hospital case load, and medical history of diabetes mellitus were significantly associated with perioperative BI deterioration in all cases and sporadic HBs. Only medical history of diabetes mellitus was a significant risk factor for perioperative BI deterioration in VHL-associated HBs., Conclusions: No differences in perioperative BI deterioration rates between sporadic HBs and VHL-associated HBs were found. However, different risk factors for perioperative BI deterioration were identified. Consideration of these risk factors is recommended in all patients undergoing surgery for HB., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study aimed to assess the risk factors for the recurrence of WHO grade I intracranial meningiomas using the Brain Tumor Registry of Japan (BTRJ) database. We extracted the data of 4641 patients with intracranial WHO grade I meningiomas treated only by surgical resection between 2001 and 2008. We conducted complete data analysis (n = 3690) and multiple imputation analysis (n = 4641) to adjust for missing data on tumor size. The influence of factors including age, sex, size, extent of resection, location, and preoperative symptoms on PFS was assessed. Univariate analyses of the complete data set showed that age did not affect PFS; however, male sex (p < 0.001), tumor size ≥ 30 mm (p < 0.001), low extent of resection, tumor location at the skull base (p < 0.001), and the presence of preoperative symptoms (p < 0.001) were risk factors for a significantly shorter PFS. Multivariate analysis demonstrated that male sex (p < 0.001) and presence of preoperative symptoms (p = 0.027) were independent risk factors for shorter PFS alongside large tumor size (p < 0.001) and non-gross total resection (p < 0.001). These results were confirmed for the imputed dataset. While most previous large nationwide studies of meningiomas have evaluated overall survival, progression-free survival has yet to be thoroughly examined. This study suggests that even histologically benign meningiomas may have a sex difference in postoperative behavior. This observation may provide clues to understanding the mechanism of meningioma cell proliferation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: In elderly populations, the enlargement of the perivascular space is related to small vessel disease and the glymphatic system. Enlarged perivascular spaces (EPVS) in the basal ganglia (EPVS-BG) and EPVS in the centrum semiovale (EPVS-CSO) are associated with different pathophysiological processes. However, the prevalence of EPVS and the factors associated with EPVS location in healthy middle-aged individuals are still unclear. We aimed to determine the prevalence of EPVS and the factors associated with EPVS location among healthy individuals in their 40 s METHODS: This study included 5000 consecutive healthy individuals who underwent screening for brain diseases in Japan from August to December 2018. Of them, the data of individuals in their 40 s were extracted and analyzed. The associations of age, sex, body mass index, smoking and drinking history, and medical history with EPVS location were investigated. Similar analyses were performed for the other age groups. A literature review on the factors associated with EPVS location was also performed., Results: A total of 1720 individuals in their 40 s were finally included. The prevalence of EPVS-BG and EPVS-CSO was 7.7% and 9.2%, respectively. Age (years), smoking history, and hypertension were associated with EPVS-BG; none of the studied factors were found to be associated with EPVS-CSO. In the elderly, the factors previously reported to be associated with EPVS-BG included atherosclerosis change, while the factors associated with EPVS-CSO were cerebral amyloid angiopathy-related formation., Conclusion: Both EPVS-BG and EPVS-CSO occurred among healthy individuals in their 40 s, but they did so rarely, and less prevalently than in older age groups. EPVS-BG and EPVS-CSO may represent early imaging signs of the atherosclerotic and cerebral amyloid angiopathy processes, respectively., Data Availability: The anonymized data for this study will be shared upon any qualified investigator's request to the corresponding author. Primary data from this study will be made available upon reasonable request in accordance with the review board of the research institute., Competing Interests: Declaration of Competing Interest Dr. Kitamura receives personal fees from Medical Network Systems, MNES Inc., related to this work. Mr. Tomoaki Hamano, as the CEO of SmartScan, Inc., receives officers' remuneration from SmartScan, Inc., and holds more than 5% of SmartScan shares. All the other authors report that they have no conflict of interest to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: The simplified 5-factor modified frailty index (mFI-5) is a useful indicator of outcome for patients undergoing surgeries as frailty is considered an important risk factor in elderly patients. However, its usefulness has not been validated based on age groups. Therefore, we aimed to investigate risk factors, including the mFI-5, across age groups for complications and worse outcomes in meningioma surgery using data obtained from the nationwide database in Japan., Methods: We extracted data from the nationwide registry database in Japan between 2010 and 2015. Age (< 65, 65-74, and ≥ 75 years), sex, Barthel Index (BI), mFI-5 scores, and complications were evaluated. Multivariate logistic regression analyses identified risk factors for worsening BI scores and complications after surgery across all age groups., Results: Among 8138 included patients, an mFI-5 score ≥ 2 items was a significant risk factor for worsening BI scores in patients aged < 65 years (odds ratio: 2.3; 95 % confidence interval: 1.5-3.4), but not in patients aged 65-74 years and those aged ≥ 75 years, contrary to chronological age. Similar results were noted for any complications in patients aged < 65 years (2.5; 1.8-3.6) and aged 65-74 years (1.5; 1.1-2.1), but not in patients aged ≥ 75 years., Conclusion: Although the mFI-5 scores could predict the risk of in-hospital worsening outcomes, mortality, and complications, it was more useful in non-elderly patients aged < 65 years rather than in elderly patients aged ≥ 75 years, contrary to chronological age. Further prospective studies should be performed in the future to clarify the utility of the mFI-5., Competing Interests: Declarations of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The "Izumo Study" revealed the incidence rate of subarachnoid hemorrhage (SAH) in Izumo City, Shimane Prefecture, Japan, from 1980 to 1998. However, no study has been published regarding the incidence of SAH in Shimane Prefecture after 1998. Most studies reporting the incidence of SAH in Japan have been conducted before 2000, although a few have been reported after 2000. This study aimed to assess the estimated age-adjusted incidence rate (AAIR) of SAH in Shimane Prefecture after 1998, following the Izumo Study. A retrospective study was conducted to identify the estimated AAIR of SAH in Shimane Prefecture, using the age-adjusted SAH mortality rate for this population from 1999 to 2017 and assuming that the case-fatality rate of SAH decreased by 0.7% annually from 45% in 1999 to 32.4% in 2017. We used linear regression analysis for trend to the estimated AAIR of SAH. Sensitivity analyses were also conducted by various case-fatality rates of SAH using assuming case-fatality rate based on previous reports. The estimated AAIR of SAH in Shimane Prefecture declined from 33.6 (95% confidence interval [CI]: 29.7-37.9) per 100,000 person-years in 1999, by 26.5%, to 24.7 (95% CI: 21.4-28.5) in 2017 (p < 0.01, r = 0.58). Declining trend of incidence rate of SAH in Shimane Prefecture from 1999 to 2017 was confirmed in this study.

Preoperative shaving and disinfection; postoperative wound care; and preoperative, intraoperative, and postoperative antibiotic use are the main methods used to prevent perioperative surgical site infection(SSI); however, a survey of neurosurgeons in Japan did not indicate that these guidelines were followed. There are several types of surgical procedures in the field of neurosurgery, including implant insertion, with little evidence of use of antimicrobial agents in such surgeries. Hence, there had been no guidelines for antimicrobial use in neurosurgery in Japan. However, practice guidelines for the appropriate use of antimicrobial agents for the prevention of postoperative infection in neurosurgery were published in 2020 and are discussed in this section.

Objective: The objective of the study was to clarify the prevalence of and factors associated with changes in patients' outcomes between discharge and 3 months after the onset of aneurysmal subarachnoid hemorrhage (aSAH). Additionally, the World Federation of Neurosurgical Societies (WFNS) and modified WFNS (mWFNS) scales were compared., Methods: The data of curatively treated patients with aSAH, collected prospectively in the mWFNS scale study between January 2010 and December 2012, were analyzed retrospectively. The improvement or decline in the modified Rankin Scale (mRS) scores between discharge and 3 months after onset was determined. A multivariable logistic regression analysis was performed to identify factors, such as age and WFNS and mWFNS grades, associated with changes in the outcome., Results: The mRS scores improved in 28.3% and declined in 2.5% of the patients. WFNS and mWFNS grades Ⅱ-V on admission were significantly associated with improved mRS scores at 3 months after onset. Older age (age: 65-74 years vs. age <65 years, odds ratio: 6.59, 95% confidence interval: 1.28-34.01; age ≥75 years vs. age <65 years, odds ratio: 17.67, 95% confidence interval: 2.11-148.26) and WFNS grade III were significantly associated with a decline in mRS scores at 3 months after onset., Conclusions: The optimal timing for postdischarge assessment of outcomes may be at 3 months after onset, especially in older patients with aSAH. The mWFNS scale is presumed to more accurately assess the outcomes of patients with aSAH than the WFNS scale, as demonstrated in this study., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: As the global population ages, the incidence of traumatic brain injury (TBI) is increasing. Whereas mild TBI can impair the cognitive function of older adults, the cause and background of mild TBI-induced cognitive impairment remain unclear, and the evaluation of risk factors for cognitive impairment after mild TBI remains open for consideration, especially in the aging population. This study aimed to evaluate the risks associated with cognitive impairment following mild TBI., Methods: Between January 2006 and December 2018, a total of 2209 patients with TBI required hospitalization in Shimane Prefectural Central Hospital. Mild TBI was defined as a Japan Coma Scale ≤10 at admission. Patients' cognitive function was measured with the Hasegawa Dementia Rating Scale-Revised or Mini-Mental State Examination at least twice during the patients' hospital stays. The odds ratio (OR) and 95% confidence interval (CI) of each considered risk factor was calculated with multivariable logistic regression analysis after univariate analysis., Results: Among 1674 patients with mild TBI, 172 patients underwent cognitive function examinations, of whom 145 (84.3%) were found to have cognitive impairment at discharge. Significant risk factors for cognitive impairment included age (P = 0.008) and hypertension (P = 0.013) in univariate analysis; and age (OR, 1.04: 95% CI, 1.01-1.07) and hypertension (OR, 5.81: 95% CI, 1.22-27.68) by multivariable analysis., Conclusions: Older patients with hypertension displayed a significantly higher risk for cognitive impairment after even mild TBI. These patients warrant careful management after even mild TBI., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This is a post hoc multivariate analysis of the modified World Federation of Neurosurgical Societies (WFNS) grading project, multicenter prospective observational study including 38 neurosurgical institutions across Japan. Japan Neurosurgical Society WFNS grading committee conducted a modified WFNS grading project as a nationwide prospective registry study. We investigate the clinical outcome of both surgical and endovascular interventions after aneurysmal subarachnoid hemorrhage (SAH) in Japan. A total of 792 patients received surgical intervention and 417 patients received endovascular treatment. Eight hundred patients were female, and 409 patients were male. The mean age was 61.5 ± 13.7 years. At 3 month follow-up, there was no statistically significant difference in good clinical outcome between surgical (68.2%) and endovascular (60.9%) group (odds ratio, 0.89; 95% confidence interval, 0.68-1.16; p = 0.381). Unfavorable outcome rate was 31.8% (238 patients) in the surgical group and 39.1% (154 patients) in the endovascular group. Male, elderly people, modified Rankin scale condition before onset, high-grade modified WFNS clinical grading scale, intracerebral hematoma, posttreatment normal pressure hydrocephalus, and neurological deficit due to symptomatic vasospasm were risk factors for the clinical outcome. Treatment modality was not a statistical factor for clinical outcomes. Surgical clipping has still a major role in the management of SAH in Japan. The present study was not a randomized controlled study, but clinical outcome is not influenced by treatment modalities.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study aimed to improve the understanding of the role of adjuvant radiotherapy (AR) after subtotal resection (STR) of World Health Organization (WHO) grade I meningiomas., Methods: We retrospectively reviewed the Brain Tumor Registry of Japan database. Among 7341 patients diagnosed with intracranial meningioma during 2001-2008, we identified 406 patients with WHO grade I meningioma treated with STR as initial treatment. Data on progression-free survival (PFS) were assessed for their relevance to clinical factors including age, sex, tumor location and size, presence of preoperative symptoms, and AR., Results: AR was administered for 73 patients (18.0%). Regrowth occurred in 90 cases (22.2%) during the median follow-up period of 6.0 years (interquartile range, 2.7-7.7 years). Multivariate Cox regression analysis of the entire cohort showed that no AR was associated with significantly shorter PFS (hazard ratio [HR] 2.52, 95% confidence interval [CI] 1.33-5.42, p = 0.004). The therapeutic effect of AR was confirmed for skull base, but not non-skull base, meningiomas (p = 0.003 and 0.69, respectively). Propensity score matching analysis balanced the influence of confounding factors to generate AR+ and AR- cohorts of 73 patients each. PFS was significantly longer in the AR+ cohort than in the AR- cohort (HR 3.46, 95% CI 1.53-8.59, p = 0.003). Subgroup analysis demonstrated the favorable effect of AR only for skull base meningiomas., Conclusions: Our study revealed that AR improves tumor control after STR in WHO grade I meningiomas. However, this beneficial effect might be limited to skull base meningiomas.

This study aimed to determine the prevalence and risk factors for brain white matter changes in normal young and middle-aged participants who underwent Brain Dock (brain screening). We analyzed 5,000 consecutive healthy participants from the Brain Dock registry between August to December 2018. Age, sex, body mass index (BMI), medical history, deep subcortical white matter high intensity (DSWMH), periventricular high intensity (PVH), and enlargement of perivascular space (EPVS) were investigated in relation to age. The prevalence of DSWMH, PVH, and EPVS were 35.3%, 14.0%, and 17.8%, respectively. Multivariate logistic regression analyses for brain white matter changes were conducted. The significant risk factors in participants aged < 50 years were: age (OR:1.09, 95% CI:1.07-1.12), the female sex (1.29, 1.03-1.60), BMI obesity (1.86, 1.12-3.08), and hypertension (1.67, 1.18-2.35) for DSWMH; age (1.08, 1.04-1.13) and the female sex (1.56, 1.03-2.36) for PVH; and age (1.07, 1.05-1.10) and the female sex (0.77, 0.60-1.00) for EPVS. In conclusion, age was consistently identified as a significant risk factor in young and middle-aged participants. Some risk factors for brain white matter changes were identified even in young and middle-aged participants in this study. Further longitudinal studies should be done in the future.

Background: Asymptomatic or minor symptom meningiomas (AMSMs) in the elderly are incidental findings, with no consensus reached on the optimal management strategy. In the present study, we aimed to determine the surgical risk factors for elderly patients with AMSMs using a nationwide registry database in Japan., Methods: We identified patients with surgically treated AMSMs using the Diagnosis Procedure Combination database from 2010 to 2015 and reviewed the medical records for age (<65 years; pre-elderly, 65-74 years; and elderly, ≥75 years), sex, Barthel index (BI) score, medical history, tumor location, and complications. An AMSM was defined by a BI score of 100 points at admission. The risk factors for all stroke complications, BI deterioration at discharge, and in-hospital mortality were determined using multivariate logistic regression analyses., Results: From a total of 10,535 patients with meningioma, 6628 were included. Advanced age was a significant risk factor (odds ratio, 3.54; 95% confidence interval, 2.80-4.46) for BI deterioration but not for all-stroke complications or in-hospital mortality. Midline and posterior fossa tumors, diabetes mellitus, and chronic heart disease were significant risk factors for in-hospital mortality., Conclusions: For elderly patients with surgically treated AMSMs, advanced age was a prominent risk factor for functional decline at discharge. Our study identified several factors that should be evaluated before proceeding with surgery for AMSMs in elderly and pre-elderly patients. These findings could, not only improve decision-making among clinicians treating patients with AMSMs, but also help in predicting the results of surgery for elderly patients with AMSMs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

There are no scoring methods for optimal treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). We developed a scoring model to predict clinical outcomes according to aSAH risk factors using data from the Japan Stroke Data Bank (JSDB). Of 5344 patients initially registered in the JSDB, 3547 met the inclusion criteria. Patients had been diagnosed with aSAH and treated with surgical clipping or endovascular coiling between 1998 and 2013. We performed multivariate logistic regression for poor outcomes at discharge, indicated by a modified Rankin Scale (mRS) score >2, and in-hospital mortality for both treatment methods. Based on each risk factor, we developed a scoring model assessing its validity using another dataset of our institution. In the surgical clipping group, scoring criteria for aSAH were age >72 years, history of more than once stroke, World Federation of Neurological Societies (WFNS) grades II-V, aneurysmal size >15 mm, and vertebrobasilar artery (VBA) aneurysm location. In the endovascular coiling group, scoring criteria were age >80 years, history of stroke, WFNS grades III-V, computed tomography (CT) Fisher group 4, and aneurysmal location in the middle cerebral artery (MCA) and anterior cerebral artery (ACA). The rates of poor outcome of mRS score >2 in an isolated dataset using these scoring criteria were significantly correlated with our model's scores, so this scoring model was validated. This scoring model can help in the more objective treatment selection in patients with aSAH.

Although surgical resection is the most preferred treatment for intracranial meningiomas, a detailed analysis of the surgery-related risks based on large population data has not been conducted to date. In this study, we analyzed the nation-wide brain tumor registry to assess the surgical risk factors for intracranial meningiomas to provide information for an optimal treatment strategy. Data of 4081 meningioma patients who underwent initial resection between 2001 and 2008 were extracted from the Brain Tumor Registry of Japan (BTRJ) database and reviewed for postoperative mortality, aggravation of Karnofsky Performance Score (KPS), and complications. The total in-hospital mortality rate was 0.59%. Male sex and tumor size ≥30 mm were independent risk factors for mortality. Among 4081 cases, 4.4% of patients had KPS that were lowered by 20 or more points at the time of discharge after surgery. Age ≥65 years, higher WHO grading, tumor location at the skull base, tumor size ≥30 mm, and non-gross total resections were associated with lowering of KPS scores by 20 or more points. The overall incidence of surgical complications was 19.3%. The rate of occurrence of new postoperative seizure in patients with supratentorial meningioma was 10.9%. All complications except for vascular complications occurred with significantly lower frequencies in asymptomatic patients than in symptomatic patients. Our results provide useful information regarding the surgical risks when surgical intervention is being considered for intracranial meningiomas. Surgery is an important option for asymptomatic meningiomas as the mortality rate and complication rate in the current study were sufficiently low.

The G-protein coupled receptor 3 (GPR3), a member of the class A rhodopsin-type GPR family, constitutively activates Gαs proteins without any ligands. Although there have been several reports concerning the functions of GPR3 in neurons, the physiological roles of GPR3 have not been fully elucidated. To address this issue, we analyzed GPR3 distribution in detail using fluorescence-based X-gal staining in heterozygous GPR3 knockout/LacZ knock-in mice, and further investigated the types of GPR3-expressing neurons using fluorescent double labeling with various EF-hand Ca 2+ -binding proteins. In addition to the previously reported GPR3-expressing areas, we identified GPR3 expression in the basal ganglia and in many nuclei of the cranial nerves, in regions related to olfactory, auditory, emotional, and motor functions. In addition, GPR3 was not only observed in excitatory neurons in layer V of the cerebral cortex, the CA2 region of the hippocampus, and the lateral nucleus of the thalamus, but also in γ-aminobutyric acid (GABA)-ergic interneurons in the cortex, hippocampus, thalamus, striatum, and cerebellum. GPR3 was frequently co-expressed with neuronal Ca 2+ -binding protein 2 (NECAB2) in neurons in various regions of the central nervous system, especially in the hippocampal CA2, medial habenular nucleus, lateral thalamic nucleus, dorsolateral striatum, brainstem, and spinal cord anterior horn. Furthermore, GPR3 also co-localized with NECAB2 at the tips of neurites in differentiated PC12 cells. These results suggest that GPR3 and NECAB2 are highly co-expressed in specific neurons, and that GPR3 may modulate Ca 2+ signaling by interacting with NECAB2 in specific areas of the central nervous system., (Copyright © 2020 Elsevier B.V. All rights reserved.)