[In-Hospital Arrangements for Preoperative Simulation].

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.

Association of the body mass index with poor outcome at discharge in patients with aneurysmal subarachnoid hemorrhage: a registry study.

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/m2) and overweight (≥ 25 kg/m2) 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).

Male sex and presence of preoperative symptoms are associated with early recurrence of WHO grade I meningiomas after surgical resection: analysis from the nationwide Brain Tumor Registry of Japan.

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.

[Practical Guidelines for the Appropriate Use of Antimicrobial Agents for Prevention of Surgical Site Infection in Various Neurosurgical Fields].

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.

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.

Effect of adjuvant radiotherapy after subtotal resection for WHO grade I meningioma: a propensity score matching analysis of the Brain Tumor Registry of Japan.

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.

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.

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.

International multicentre validation of the arteriovenous malformation-related intracerebral haemorrhage (AVICH) score.

OBJECTIVE: The recently published arteriovenous malformation-related intracerebral haemorrhage (AVICH) score showed better outcome prediction for patients with arteriovenous malformation (AVM)-related intracerebral haemorrhage (ICH) than other AVM or ICH scores. Here we present the results of a multicentre, external validation of the AVICH score. METHODS: All participating centres (n=11) provided anonymous data on 325 patients to form the Spetzler-Martin (SM) grade, the supplemented SM (sSM) grade, the ICH score and the AVICH score. Modified Rankin score (mRS) at last follow-up (mean 25.6 months) was dichotomized into favourable (mRS 0-2, n=210) and unfavourable (mRS 3-6;n=115). Univariate and AUROC analyses were performed to validate the AVICH score. RESULTS: Except nidus structure and AVM size, all single parameters forming the SM, sSM, ICH and AVICH score and the scores itself were significantly different between both outcome groups in the univariate analysis. The AVICH score was confirmed to be the highest predictive outcome score with an AUROC of 0.765 compared with 0.705 for the ICH score and 0.682 for the sSM grade. CONCLUSION: The multicentre-validated AVICH score predicts clinical outcome superior to pre-existing scores. We suggest the routine use of this score for future clinical outcome prediction and in clinical research. TRIAL REGISTRATION NUMBER: NCT02920645.

Ruptured dissecting aneurysms of the A1 segment of the anterior cerebral artery: three case reports and a review of the literature.

Dissecting aneurysms in the anterior cerebral artery (ACA), although rare, can cause ischemic and/or hemorrhagic stroke. Hemorrhagic dissecting aneurysms in the A1 portion of the ACA are often associated with a poor prognosis. We retrospectively investigated three rare cases of hemorrhagic dissecting aneurysms in the A1 portion. Dissecting aneurysms were diagnosed by carotid angiography or computed tomography angiography to visualize morphological changes in the vessel. All patients presented with diffuse subarachnoid hemorrhage. In one case, computed tomography angiography performed at the onset of the subarachnoid hemorrhage revealed fusiform dilatation at the right ACA (A1), which did not appear on a magnetic resonance angiogram obtained 1 year prior to the onset of the subarachnoid hemorrhage. In the other two cases, A1 dissecting aneurysms were diagnosed from a growing aneurysmal bulge revealed at a non-bifurcated site via repeated carotid angiography. Two patients underwent surgical intervention (trapping or clipping), and their outcome was favorable, whereas the third patient died of delayed rebleeding before receiving surgical treatment. Hemorrhagic dissecting aneurysms in the A1 portion cause severe subarachnoid hemorrhage. Surgical treatments that include revascularization are necessary to prevent rebleeding, and direct surgery is recommended, particularly at the A1 portion.

Analysis of outcome at discharge after aneurysmal subarachnoid hemorrhage in Japan according to the Japanese stroke databank.

The outcomes at discharge for ruptured cerebral aneurysms after subarachnoid hemorrhage (SAH) were investigated using data from the Japanese stroke databank. Among 101,165 patients with acute stroke registered between 2000 and 2013, 4693 patients had SAH caused by ruptured saccular aneurysm. Of these, 3593 patients (1140 men and 2453 women; mean age 61.3 ± 13.7 years) were treated by surgical clipping (SC) and/or endovascular coiling (EC). The outcomes of modified Rankin scale (mRS) at discharge were compared between the SC and EC groups. There were 2666 cases in the SC group, 881 cases in the EC group, and 46 cases in the SC and EC group. The rates of poor outcome of mRS > 2 were 33.0 and 45.5% in the SC and EC groups (p < 0.05), respectively. Cases were selected using two types of criteria compatible with both treatments. Under the first compatible criteria, the rates of poor outcome of mRS > 2 were 18.9 and 24.8% in the SC and EC groups (p < 0.05), respectively. Under the second compatible criteria, the rates of poor outcome of mRS > 2 were 16.0 and 14.8% in the SC and EC groups (p = 0.22), respectively. No significant differences were found in clinical characteristics or outcomes between the two groups. Multivariate analysis of aneurysmal SAH revealed no significant risk for poor outcome associated with the treatment method. The present study was not a randomized controlled study, but no significant differences in mRS at discharge were found between SC and EC in the Japanese stroke databank.

Effect of actual age on outcome at discharge in patients by surgical clipping and endovascular coiling for ruptured cerebral aneurysm in Japan.

The Japanese population features the highest rate of elderly individuals worldwide. However, the difference of actual age indication for surgical clipping (SC) and endovascular coiling (EC) has never reported. We clarified the effect of actual age on poor outcome at discharge in patients by each treatment for ruptured cerebral aneurysm according to the Japanese Stroke Data Bank. A total of 3593 patients with ruptured saccular cerebral aneurysm were treated by SC and/or EC between 2000 and 2013. The effect of actual age on poor outcome (modified Rankin scale [mRS] score > 2) at discharge was evaluated by the cutoff age using receiver operating characteristic analysis for each treatment. There were 2666 cases in the SC group and 881 cases in the EC group. The cutoff age for poor outcome was 3 to 9 years older for EC than for SC. The gap of cutoff age between two treatments was 3 years shorter in mild subarachnoid hemorrhage than severe cases. The gap of cutoff age between two treatments was 7 years in elderly patients over 65 years old. The cutoff age was 78 years old for both SC and EC in elderly female patients. In conclusion, the cutoff age for poor mRS score > 2 was 3 to 9 years older for EC than for SC. Actual age was one of the indications for elderly patients to achieve the optimum outcome; however, the treatment indication should be carefully considered based on the condition in each country.

Multivariate risk factor analysis and literature review of postoperative deterioration in Karnofsky Performance Scale score in elderly patients with skull base meningioma.

OBJECTIVE Elderly patients are particularly at risk for severe morbidity following surgery. Among the various risk factors, age and skull base location of meningioma are known to be poor prognostic factors in meningioma surgery. The authors conducted this study to analyze significant preoperative risk factors in elderly patients with skull base meningioma. METHODS A total of 265 elderly patients (≥ 65 years old) with meningioma were surgically treated at the authors' institute and affiliated hospitals between 2000 and 2016, and these cases were reviewed. Among them, 57 patients with skull base meningioma were evaluated. Among the various risk factors, the authors analyzed age, sex, Karnofsky Performance Scale (KPS) score, American Society of Anesthesiologists score, and tumor size, location, and pathology. Body mass index (BMI) and serum albumin were investigated as the frailty factors. The authors also reviewed 11 surgical studies of elderly patients ≥ 60 years old with meningioma. RESULTS The mean age was 72.4 ± 5.7 years, and 42 patients were female (73.6%). The mean size of meningioma was 36.6 ± 14.8 mm at the maximum diameter, and the mean follow-up period was 31.1 ± 31.5 months. (The continuous variables are expressed as the mean ± SD.) Histopathological investigation revealed a higher incidence (71.9%) of WHO Grade I. The rates of deterioration after surgery, at 3 months, and at 1 year were 33.3%, 37.3%, and 39.1%, respectively. Univariate analysis revealed location, preoperative KPS score, BMI level 2, and serum albumin level (p = 0.010, 0.017, 0.0012, and 0.0019, respectively) to be poor prognostic factors. Multivariate analysis revealed that location (p = 0.038) and BMI (p = 0.035) were risk factors for KPS score deterioration immediately after surgery. According to the 11 papers reviewed, the median rate (25th-75th percentile) of skull base-related location was 43.5% (39.6-47.75); for asymptomatic status the mean was 24%; and for mortality at 3 months and 1 year the medians were 6.3% (0.7-7.1) and 8% (4.8-9.4), respectively. CONCLUSION Careful preoperative assessment based on the frailty concept was essential for better outcome in elderly patients with skull base meningioma. The BMI is appropriate as a quantitative factor for measure of frailty, particularly in elderly individuals with skull base meningioma. Further prospective randomized controlled trials are necessary to validate frailty as a preoperative risk factor. Not only patient selection but also surgical timing was an important factor.

Preoperative simulation of the running course of the abducens nerve in a large petroclival meningioma: a case report and literature review.

One of the most important and useful pieces of information in the preoperative evaluation of a large petroclival meningioma is the running course of the abducens nerve. The abducens nerve is small and has a long intracranial course, making it prone to compression by the tumor at various anatomical points. In relatively large tumors, it is difficult to confirm the entire course of the abducens nerve, even by heavy T2-thin slice imaging. We report a case of successful preoperative estimation of the course of the abducens nerve that aided in its complete preservation during the resection of a large petroclival tumor.

[A Case of Cervical Spinal Dural Arteriovenous Fistula with Extradural Drainage Presenting with Subarachnoid Hemorrhage due to a Ruptured Anterior Spinal Artery Aneurysm].

We report a rare case of a cervical spinal dural arteriovenous fistula(AVF)at the C2 level presenting with subarachnoid hemorrhage(SAH)due to a ruptured anterior spinal artery aneurysm. A 61-year-old man presented with sudden onset headache. Initial computed tomography revealed SAH around the brainstem. Digital subtraction angiography(DSA)demonstrated a cervical dural AVF that was fed by the left C1 radicular, left C2 radicular, and anterior spinal arteries, and drained into the epidural plexus. An aneurysm in the branch of the cervical anterior spinal artery was considered the bleeding point. A left lateral suboccipital craniotomy and C1 hemilaminectomy were performed on day 43. The feeding arteries were clipped, followed by coagulation of the draining veins. However, the aneurysm was not clipped because we deemed that obliteration of the aneurysm would be difficult without disrupting the blood flow of the parent artery. The patient showed no neurological deterioration after the operation. Postoperative DSA revealed residual dural AVF. Therefore, a second surgery was performed. After the second open surgery, DSA showed that the dural AVF and aneurysm disappeared. The patient also showed no neurological deterioration after the second surgery.

[Gender difference in cerebrovascular disease].

We discuss about the gender difference of cerebrovascular disease according to the data of Japan Standard Stroke Registry Study. The male proportion was dominant in cerebrovascular disease except for subarachnoid hemorrhage(SAH). According to the data of Ministry of Health, Labour and Welfare, age-adjusted death rate in cerebral infarction and intracerebral hemorrhage were higher in male than in female, however, in SAH the rate was no different between male and female. The incidence of SAH is higher in women than in men, but this gender difference emerges not earlier than age 59. Most cases of SAH were occurring in the ages ranging from 50's in male and 70's in female. The total male-to-female ratio was approximately 1:2. The female proportion was dominant in older patients.

[A case of cavernous angioma at the convexity in the dura mater: characteristics of images in the literature].

We describe a rare case of cavernous angioma in the dura mater and discuss published MRI findings on similar cases. The patient was a 78-year-old woman who was referred to Shimane Prefectural Central Hospital with complaints of headaches. We were subsequently able to identify a tumor at the convexity in the dura mater. The tumor showed a high intensity on T2-weighted images and was heterogeneously enhanced on contrast-enhanced T1-weighted images. The maximum size of the tumor was 35 mm. Moreover, preoperative angiography showed a slight vascularity in the tumor. We performed surgery with the expectation of finding a meningioma, metastatic brain tumor, or another mesenchymal tumor. The tumor was dark and red, attached to the dura mater, and adhered to the arachnoid. However, we were able to peel the tumor away from the meninges and achieved a total removal of the mass, successfully cutting a fine feeding cortical artery. The patient was discharged without neurological defects 9 days after surgery;the pathological diagnosis was cavernous angioma. In conclusion, it is difficult to discern between meningioma and cavernous angioma in the dura mater. However, the specificity of high intensity on T2-weighted images is relatively high, and preoperative diagnosis can be determined by MRI and angiography findings.

Surgical Risk in Elderly Patients with Meningiomas in Japan.

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.

Artificial intelligence for volumetric measurement of cerebral white matter hyperintensities on thick-slice fluid-attenuated inversion recovery (FLAIR) magnetic resonance images from multiple centers.

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.

Allogeneic Stem Cell Therapy for Acute Ischemic Stroke: The Phase 2/3 TREASURE Randomized Clinical Trial.

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.