Classification and hemodynamic characteristics of delayed intracerebral hemorrhage following stent-assisted coil embolism in unruptured intracranial aneurysms.

Background and objective: Stent-assisted coil (SAC) embolization is a commonly used endovascular treatment for unruptured intracranial aneurysms (UIAs) but can be associated with symptomatic delayed intracerebral hemorrhage (DICH). Our study aimed to investigate the hemodynamic risk factors contributing to DICH following SAC embolization and to establish a classification for DICH predicated on hemodynamic profiles. Methods: This retrospective study included patients with UIAs located in the internal carotid artery (ICA) treated with SAC embolization at our institution from January 2021 to January 2022. We focused on eight patients who developed postoperative DICH and matched them with sixteen control patients without DICH. Using computational fluid dynamics, we evaluated the hemodynamic changes in distal arteries [terminal ICA, the anterior cerebral artery (ACA), and middle cerebral artery (MCA)] pre-and post-embolization. We distinguished DICH-related arteries from unrelated ones (ACA or MCA) and compared their hemodynamic alterations. An imbalance index, quantifying the differential in flow velocity changes between ACA and MCA post-embolization, was employed to gauge the flow distribution in distal arteries was used to assess distal arterial flow distribution. Results: We identified two types of DICH based on postoperative flow alterations. In type 1, there was a significant lower in the mean velocity increase rate of the DICH-related artery compared to the unrelated artery (-47.25 ± 3.88% vs. 42.85 ± 3.03%; p < 0.001), whereas, in type 2, there was a notable higher (110.58 ± 9.42% vs. 17.60 ± 4.69%; p < 0.001). Both DICH types demonstrated a higher imbalance index than the control group, suggesting an association between altered distal arterial blood flow distribution and DICH occurrence. Conclusion: DICH in SAC-treated UIAs can manifest as either a lower (type 1) or higher (type 2) in the rate of velocity in DICH-related arteries. An imbalance in distal arterial blood flow distribution appears to be a significant factor in DICH development.

RACK1 Promotes Meningioma Progression by Activation of NF-κB Pathway via Preventing CSNK2B from Ubiquitination Degradation.

Higher-grade meningiomas (WHO grade II and III) are characterized by aggressive invasiveness and high postoperative recurrence rates. The prognosis remains inadequate even with adjuvant radiotherapy and currently there is no definitive pharmacological treatment strategy and target for malignant meningiomas. This study aims to unveil the mechanisms driving the malignant progression of meningiomas and to identify potential inhibitory targets, with significant clinical implications. Implementing techniques such as protein immunoprecipitation, mass spectrometry, RNA interference, and transcriptome sequencing, we investigated the malignancy mechanisms in meningioma cell lines IOMM-LEE and CH157-MN. Additionally, in vivo experiments were carried out on nude mice. We discovered a positive correlation between meningioma malignancy and the levels of the receptor for activated C kinase 1 (RACK1), which interacts with CSNK2B, the ß subunit of casein kinase 2 (CK2), inhibiting its ubiquitination and subsequent degradation. This inhibition allows CK2 to activate the NF-κb pathway, which increases the transcription of CDK4 and cyclin D3, resulting in the transition of the cell cycle into the G2/M phase. The RACK1 inhibitor, harringtonolide (HA), significantly suppressed the malignant tendencies of meningioma cells. Our study suggests that RACK1 may play a role in the malignant progression of meningiomas, and therefore, targeting RACK1 could emerge as an effective strategy for reducing the malignancy of these tumors.

Overlapping Stent Treatment for Ruptured Dissecting Aneurysms in Posterior Circulation.

Ruptured dissecting aneurysms in posterior intracranial circulation present significant clinical challenges and often cause poor prognoses. Our cohort used overlapping stents as the primary treatment. We analyzed the medical records of 27 patients (18 men/nine women) with ruptured posterior circulation dissecting aneurysms (PCDAs). Their average age was 52 years. We selected 11 patients who used Enterprise (EP) and LVIS stents overlappingly and matched them 1:1 with counterparts who received either EP or LVIS stents individually. Overlapping stents was a feasible treatment in all 27 cases. We successfully followed up 26 patients for ≥6 months. Regrettably, one patient died from intracranial hypertension on Day 7 post-procedure. Immediate post-procedure angiographies indicated Raymond grade I, II, and III occlusions of PCDAs in 16 (59.3%), 7 (25.9%), and 4 (14.8%) cases, respectively. At an average follow-up duration of 16.2 months, 25 patients (96.2%) had modified Rankin Scale scores of 0-2, signifying positive outcomes. One patient (3.8%) had a score of 3-4. Recurrence rates for the EP and LVIS stent groups were higher than those of the overlapping stent group (45.45% vs. 9.09%, p = 0.15 and 27.27% vs. 9.09%, p = 0.59, respectively). No significant difference in recurrence rates existed between the overlapping and single-stent groups. Similarly, follow-up outcomes were consistent between the two groups. Overlapping stents could be an efficient method for treating ruptured PCDAs.

Microsurgical Treatment of Arteriovenous Malformations: A Single-Center Study Experience.

OBJECTIVE: The purpose of the study was to assess the functional outcomes after microsurgical resection of arteriovenous malformations (AVMs) and to compare the results between patients eligible for A Randomized Trial of Unruptured Brain Arteriovenous Malformations in this surgical series to the results reported and the ARUBA study. METHODS: We reviewed the records of 169 patients who underwent microsurgical treatment of arteriovenous malformation (AVMs) in our institution between January 2016 and December 2021. These patients' functional status was assessed using modified Rankin Scale (mRS) scores at the last follow-up and before treatment. The mRS scores at the latest follow-up were classified into good outcomes (mRS < 3) and poor outcomes (mRS ≥ 3). Clinical presentation, patients' demographics, AVM characteristics, follow-up time, and obliteration rate were analyzed. Subgroup analyses were performed on the whole cohort, comparing Spetzler-Martin Grade I and Grade II, and ARUBA-eligible AVMs. RESULTS: The initial hemorrhagic presentation occurred in 71 (42%) out of 169 patients. The majority of the patients presented with headaches (73%). The AVMs were completely obliterated in 166 (98.2%) patients. The series included 65 Spetzler-Martin Grade I (38.5%), 46 Grade II (27.2%), 32 Grade III (18.9%), 22 Grade IV (13%), and 4 Grade V (2.4%) AVMs. There were 98 unruptured and 79 ARUBA-eligible cases. Also, optimal functional outcome was achieved in 145 (85.8%) patients. The overall mortality rate was 5.3% (9/169). The multivariate analysis illustrated that a poor outcome was significantly associated with presurgical mRS ≥3 (p < 0.013; OR, 0.206; 95% CI 0.059-0.713), increasing age (p < 0.045; odds ratio [OR], 1.022; 95% CI 1.000-0.045), and female gender (p < 0.009; OR, 2.991; 95% CI 1.309-6.832). CONCLUSIONS: Our study suggests that better outcomes can be obtained using microsurgical resection in the majority of patients with AVMs. Independent predictors of poor outcomes after surgical resection of AVMs include increasing age at the time of surgery, poor presurgical functional status, and female gender. Supposing that patients are more suitable for microsurgery after presurgical examination, outcomes are normally better in that case than those achieved by multimodal interventions (such as conservative treatment or ARUBA treatment arm). Therefore, we recommend early surgical removal on all surgically accessible AVMs to prevent successive hemorrhages and the consequences of poor neurological outcomes.

Glioma Shapes Blood-Brain Barrier Integrity and Remodels the Tumor Microenvironment: Links with Clinical Features and Prognosis.

BACKGROUND: The presence of the blood-brain barrier (BBB) uniquely distinguishes the brain from other organs, and various brain pathologies, including cancer, can disrupt or breach the BBB. The specific implications of BBB alterations in glioma have not been sufficiently clarified. METHODS: In this study, statistical analysis of the TCGA pan-glioma dataset and four other validation cohorts was used to investigate the infiltration of BBB constituent cells (endothelial cells, pericytes and astrocytes) in the glioma tumor microenvironment (TME). RESULTS: We found that the infiltration proportions of the three BBB constituent cell types were highly collinear, which implied alteration of the BBB. Hence, we developed an index, the BBB score, which is calculated based on the infiltration proportion of BBB constituent cells. Furthermore, we observed that patients with higher BBB scores were more likely to be diagnosed with more malignant entities in the TCGA database according to significant molecular features, such as IDH mutation status and 1p/19q deletion. The BBB score was also strikingly positively correlated with WHO grade in other cohorts. More importantly, a higher BBB score correlated with shorter survival time and unfavorable prognosis in glioma patients. Finally, we showed that TME-related pathways may regulate BBB alterations and that coinhibitory immune checkpoints were enriched in samples with higher BBB scores. CONCLUSIONS: We showed that TME-related pathways may regulate BBB alterations and that coinhibitory immune checkpoints were enriched in samples with higher BBB scores. Assessing BBB alterations may help elucidate the complex role of the glioma TME and suggest new combination treatment strategies.