Loss of methylthioadenosine phosphorylase immunoreactivity correlates with poor prognosis and elevated uptake of 11C-methionine in IDH-mutant astrocytoma.

PURPOSE: The proximate localization of MTAP, which encodes methylthioadenosine phosphorylase, and CDKN2A/B on Chromosome 9q21 has allowed the loss of MTAP expression as a surrogate for homozygous deletion of CDKN2A/B. This study aimed to determine whether MTAP status correlates with clinical outcomes and 11C-methionine uptake in astrocytomas with IDH mutations. METHODS: We conducted immunohistochemistry for MTAP in 30 patients with astrocytoma, IDH-mutant who underwent 11C-methionine positron emission tomography scans prior to surgical resection. The tumor-to-normal (T/N) ratio of 11C-methionine uptake was calculated using the mean standardized uptake value (SUV) for tumor and normal brain tissues. Cox regression analysis was used for multivariate survival analysis. RESULTS: Among IDH-mutant astrocytomas, 26.7% (8/30) exhibited the loss of cytoplasmic MTAP expression, whereas 73.3% (22/30) tumors retained MTAP expression. The median progression-free survival (PFS) was significantly shorter in patients with MTAP loss than those with MTAP retention (1.88 years vs. 6.80 years, p = 0.003). The median overall survival (OS) was also shorter in patients with MTAP loss than in MTAP-retaining counterparts (5.23 years vs. 10.69 years, p = 0.019). Multivariate analysis identified MTAP status (hazard ratio (HR), 0.081) and extent of resection (HR, 0.104) as independent prognostic factors for PFS. Astrocytomas lacking cytoplasmic MTAP expression showed a significantly higher median T/N ratio for 11C-methionine uptake than tumors retaining MTAP (2.12 vs. 1.65, p = 0.012). CONCLUSION: Our study revealed that the loss of MTAP expression correlates with poor prognosis and an elevated T/N ratio of 11C-methionine uptake in astrocytoma, IDH-mutant.

Efficacy of endovascular treatment for distal anterior cerebral artery aneurysms: A multicenter observational study.

OBJECTIVES: Distal anterior cerebral artery (DACA) aneurysms account for 1%-9% of all intracranial aneurysms. Microsurgical treatment is generally preferred for DACA aneurysms; however, it presents challenges owing to the anatomical complexities. Advances in neuro-interventional techniques have yielded promising results. This study aims to compare the clinical outcomes of DACA aneurysms treated with microsurgery and endovascular treatment (EVT) to elucidate the efficacy of EVT. MATERIALS AND METHODS: A multicenter observational registry comprising 16 stroke centers was utilized for this study. Data was retrospectively and prospectively analyzed from 166 patients with DACA aneurysms in our database, which included 4,552 consecutive patients with ruptured or unruptured intracranial aneurysms who underwent microsurgical or endovascular treatment between January 2013 and December 2021. RESULTS: Surgical clipping was performed in 115 patients, and 51 underwent coil embolization. The median follow-up duration was 15.3 months. No significant differences were observed in patient characteristics between the two treatment modalities. There were no differences in complication-related morbidity between the microsurgical treatment and EVT groups in either unruptured (10.5% vs. 9.1%, p=1.00) or ruptured aneurysms (5.2% vs. 6.9%, p=0.66). Coil embolization resulted in higher recurrence and retreatment rates than surgical clipping did, especially for ruptured aneurysms (2.6% vs. 27.6%, p<0.01). CONCLUSIONS: Endovascular treatment is an alternative to microsurgery for DACA aneurysms especially in unruptured cases or the patients who have difficulty undergoing craniotomy due to their general condition, albeit with considerations for higher recurrence and retreatment rates, particularly in ruptured cases. Close follow-up is crucial for the effective management of these challenges. Further studies are needed to refine the treatment strategies for DACA aneurysms.

Quantitative collateral assessment evaluated by cerebral blood volume measured by CT perfusion in patients with acute ischemic stroke.

OBJECTIVES: Collateral status (CS) is considered a predictor of clinical outcome after reperfusion therapy (RT) in patients with acute ischemic stroke (AIS). We proposed a quantitative assessment of CS using cerebral blood volume (CBV) measured by computed tomography perfusion (CTP) imaging. MATERIALS AND METHODS: This retrospective study was approved by the Institutional Review Board. Between February 2019 and September 2020, 60 patients with anterior circulation large-vessel occlusion who presented to our institution within 8 h after stroke onset were included. The ratio of the average CBV values in the affected middle cerebral artery (MCA) territories to the unaffected side was defined as the CBV ratio. CS was assessed by scores from previously reported qualitative scoring systems (Tan & regional leptomeningeal collateral (rLMC) scores). RESULTS: The CBV ratio was an independent factor contributing to a good functional outcome (P<0.01) and was significantly correlated with the Tan score (ρ=0.73, P<0.01) and the rLMC score (ρ=0.77, P<0.01). Among the patients with recanalization, the CBV ratio was a useful parameter that predicted both a good functional outcome (area under the receiver operating characteristic curve (AUC-ROC), 0.76; 95% CI, 0.55-0.89) and a good radiological outcome (AUC-ROC, 0.90; 95% CI, 0.72-0.97), and it was an independent predictor for good radiological outcome (OR: 4.38; 95% CI:1.29-14.82; P<0.01) in multivariate models. CONCLUSIONS: The CBV ratio is a suitable parameter for evaluating CS quantitatively for patients with AIS that can predict patient response to recanalization.

A thoracic CT imaging parameter predicting access difficulty in acute stroke thrombectomy.

PURPOSE: The quick establishment of adequate vascular access is essential for the technical success of mechanical thrombectomy (MT). Focusing on shifts in aortic arch geometry and aging-related changes, we propose an imaging parameter for predicting access difficulty using chest CT. METHODS: Patients with acute anterior circulation large-vessel occlusion who underwent MT from April 2020 to September 2021 were included in this retrospective multicenter observational study. The distance from the sternum to the ascending aorta (S-AAD) was defined as the surrogate marker of access difficulty. Access was defined as difficult when the time from femoral sheath placement to guiding catheter induction (guiding time: GT) ≥ 30 minutes, and the patients were dichotomized into groups with short GT (sGT: GT < 30 min) and long GT (lGT: GT ≥ 30 min). RESULTS: One hundred fifteen patients were included. There were 12 patients (10.4 %) in lGT group. The median (IQR) S-AAD was 11.9 mm (6.3, 18.3 mm) in sGT group and 6.6 mm (4.0, 10.3 mm) in lGT group, and a significant difference in S-AAD was observed (P = 0.026). In multivariate analyses, dyslipidemia and S-AAD < 5 mm were significantly associated with difficult access (OR, 5.938 [95 % CI, 1.468, 24.022], P = 0.012 for dyslipidemia; OR, 5.147 [95 % CI, 1.267, 20.917], P = 0.022 for S-AAD < 5 mm). CONCLUSION: S-AAD is a simple and reliable imaging parameter to predict access difficulty. This parameter may be helpful in selecting the appropriate devices and access routes in preinterventional practice.

Contact aspiration for basilar artery occlusion safely reduces the puncture-to-recanalization time.

OBJECTIVE: Effective thrombectomies in the posterior circulation remain controversial. Previous reports have demonstrated the superiority of contact aspiration in anterior circulation. Aspiration catheters and stent retrievers are often used alone on a global scale, while combined techniques are commonly used in Japan. This study evaluated the effect of first-line contact aspiration with other strategies for the treatment of basilar artery occlusion. METHODS: The primary outcome was the frequency of the first-pass effect, and the secondary outcome was the time from puncture to the first-pass effect. A multicenter observational registry including 16 Japanese stroke centers was used. Between December 2013 and February 2021, enrolled patients underwent endovascular thrombectomy for basilar artery occlusion. The efficacy of contact aspiration compared to other methods (including stent retrievers and combined techniques) was evaluated. RESULTS: Eighty-four patients were included, all of whom had achieved effective recanalization. Twenty-six patients were treated with contact aspiration, 13 with combined technique, and 45 with stent retrievers. The two groups: contact aspiration and non-contact aspiration, had different backgrounds. Both had similar frequencies of effective recanalization and first-pass effects. The contact aspiration group experienced better functional outcomes without statistical significance, while this strategy was significantly associated with a shorter puncture-to-recanalization time (38 vs. 55 minutes, P=0.036). In particular, in the 55 patients with the first-pass effect, multivariate Cox proportional hazard analysis showed that contact aspiration was significantly associated with a shorter time from puncture to first-pass effect, independent of age and etiology of large-artery atherosclerosis (hazard ratio 2.02, 95% confidence intervals 1.10-3.69, P=0.023). CONCLUSION: This study suggested that contact aspiration for basilar artery occlusion may shorten the puncture-to-first-pass effect, compared to stent retrievers and combined techniques.

Study protocol of the ASTOP trial: A multicenter, randomized, double-blind, placebo-controlled trial of presurgical aspirin administration for the prevention of thromboembolic complications of coil embolization for ruptured aneurysms.

RATIONALE: Thromboembolism is a serious complication of endovascular treatment for ruptured cerebral aneurysms. The administration of antiplatelet agents before endovascular treatment for ruptured cerebral aneurysms may reduce the risk of thromboembolic complications. AIM: This study aimed to assess the safety and efficacy of preoperative aspirin administration in endovascular treatment for ruptured cerebral aneurysms. SAMPLE SIZE ESTIMATES: Assuming a 15% incidence rate of both intraoperative thromboembolic morbidity and symptomatic ischemic lesions on magnetic resonance imaging diffusion-weighted imaging scans assessed by an Independent Review Committee, a sample size of 484 will be required to detect a 10% improvement with aspirin administration with 90% power using the Pearson's chi-square test at a two-sided significance level of 2.5% for each primary outcome, after accounting for a 5% dropout rate. METHODS AND DESIGN: ASTOP is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 484 patients with ruptured cerebral aneurysms receiving coil embolization within 72 h of onset will be randomly assigned 1:1 to receive 200 mg of aspirin or placebo before the procedure. STUDY OUTCOMES: The primary outcomes will be the incidence rates of intraoperative thromboembolic complications and symptomatic ischemic lesions on magnetic resonance imaging diffusion-weighted imaging scans evaluated by the Independent Review Committee. The secondary outcomes will be the incidence rate of cerebral ischemic events and all bleeding events within 14 days of enrollment and functional outcomes defined by the modified Rankin Scale score at 90 days. DISCUSSION: This trial will provide valuable data on the role of antiplatelet agents during endovascular treatment for ruptured cerebral aneurysms. TRIAL REGISTRATION: Registration: Japan Registry of Clinical Trials, Identifier: jRCTs031210421.

Influence of Bilateral Cerebellar Infarction on Functional Outcome After Endovascular Treatment for Basilar Artery Occlusion.

BACKGROUND AND PURPOSE: To measure the magnitude of the effect of the infarct location measured using the posterior circulation Alberta Stroke Program Early Computed Tomographic Score (pc-ASPECTS) on the functional outcome at 90 days in patients with basilar artery (BA) occlusion undergoing endovascular therapy (EVT). METHODS: Of the acute ischemic stroke patients undergoing EVT for acute posterior circulation large vessel occlusion enrolled in the multicenter observational registry from December 2013 to February 2021, patients with BA occlusion were included. A favorable outcome was defined as achieving a modified Rankin Scale score of 0-3 at 90 days. The effect of pc-ASPECTS including the distribution on favorable outcomes was evaluated. RESULTS: One hundred patients were analyzed. Fifty-one patients (51%) achieved favorable outcome. Patients achieving a favorable outcome were younger, had a lower National Institutes of Health Stroke Scale score before EVT, and had a higher pc-ASPECTS before EVT than those not achieving a favorable outcome. Multivariable logistic analysis showed a significant association between higher pc-ASPECTS and a favorable outcome (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.02-1.52; P = 0.028). Considering the infarct location, bilateral cerebellar infarction was significantly associated with a lower frequency of favorable outcomes than those without cerebellar infarction (OR 0.16; 95% CI 0.04-0.51; P = 0.002). CONCLUSIONS: A higher pc-ASPECTS before EVT could be a predictor of a favorable outcome after EVT for BA occlusion. In particular, the presence of bilateral cerebellar infarction before EVT was significantly associated with a lower likelihood of a favorable outcome.

Correlation between the CT Perfusion Parameter Values and Response to Recanalization in Patients with Acute Ischemic Stroke.

Objective: CT perfusion (CTP) provides various hemodynamic parameters. However, it is unclear which CTP parameters are useful in predicting clinical outcome in patients with acute ischemic stroke (AIS). Methods: Between February 2019 and June 2021, patients with anterior circulation large-vessel occlusion who achieved successful recanalization within 8 hours after stroke onset were included. The relative CTP parameter values analyzed by the reformulated singular value decomposition (SVD) method in the affected middle cerebral artery territories compared to those in the unaffected side were calculated. In addition, the ischemic core volume (ICV) was evaluated using a Bayesian Vitrea. The final infarct volume (FIV) was assessed by 24-hour MRI. The correlation between these CTP-derived values and clinical outcome was assessed. Results: Forty-two patients were analyzed. Among the CTP-related parameters, the ICV, relative cerebral blood volume (rCBV), and relative mean transit time (rMTT) showed a strong correlation with the FIV (ρ = 0.74, p <0.0001; ρ = -0.67, p <0.0001; and ρ = -0.66, p <0.0001, respectively). In multivariate analysis, rCBV, rMTT, and ICV were significantly associated with good functional outcome, which was defined as a modified Rankin Scale score ≤2 (OR, 6.87 [95% CI, 1.20-39.30], p = 0.0303; OR, 11.27 [95% CI, 0.97-130.94], p = 0.0269; and OR, 36.22 [95% CI, 2.78-471.18], p = 0.0061, respectively). Conclusion: Among the CTP parameters analyzed by the SVD deconvolution algorithms, rCBV and rMTT could be useful imaging predictors of response to recanalization in patients with AIS, and the performances of these variables were similar to that of the ICV calculated by the Bayesian Vitrea.

Proposal of Treatment Strategies for Bilateral Chronic Subdural Hematoma Based on Laterality of Treated Hematoma.

BACKGROUND: Chronic subdural hematoma (CSDH) is a disorder that is commonly seen in routine neurosurgery. Although risk factors for recurrence have been studied, the findings are inconsistent. Furthermore, bilateral CSDHs are operated unilaterally or bilaterally depending on symptoms or hematoma volume. Although there are cases in which hematomas on nonoperated side in unilaterally operated bilateral CSDHs requiring for additional operation, little have been studied on the effect of the surgical selection. The purpose of this study is to identify risk factors for recurrence in operated hematomas and additional operation in nonoperated hematomas and improve surgical strategy. MATERIALS AND METHODS: We retrospectively reviewed patients who underwent surgery in our facility for bilateral CSDHs between January 2011 and December 2016. Univariate and multivariate analyses were performed to examine the relationship between recurrence or requirement for additional operation and clinical and radiological variables. RESULTS: Recurrence was observed significantly more frequent for operated hematomas when hematoma type was separated type as reported previously. In unilaterally operated bilateral CSDHs, there were 22 hematomas on nonoperated side, and five hematomas required an additional operation after the first hospitalization. Increased volume of hematoma on the nonoperated side was the risk factors for additional operation (P = 0.022). Receiver operating characteristic (ROC) curve revealed that requirement for additional operation significantly increased when hematoma volume enlarged to approximately 44 cm3 or greater 1 day after operation. CONCLUSIONS: In unilaterally operated bilateral CSDHs, when hematoma volume on nonoperated side increased 1 day after the last operation, additional operation in the early stage is considerable to prevent re-hospitalization and deterioration of activities of daily living.