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Moyamoya disease (MMD) is a cerebrovascular disorder marked by progressive arterial narrowing, categorized into six stages known as Suzuki stages based on angiographic features. Growing evidence indicates a pivotal role of systemic immune and inflammatory responses in the initiation and advancement of MMD. This study employs high-dimensional mass cytometry to reveal the immunophenotypic characteristics of peripheral blood immune cells (PBMCs) at various Suzuki stages, offering insights into the progression of MMD. PBMC samples from eight patients with early-stage MMD (Suzuki stages II and III) and eight patients with later-stage MMD (Suzuki stages IV, V, and VI) were analyzed using high-dimensional mass cytometry to evaluate the frequency and phenotype of immune cell subtypes. We identified 15 cell clusters and found that the immunological features of early-stage MMD and later-stage MMD are composed of cluster variations. In this study, we confirmed that, compared to later-stage MMD, the early-stage MMD group exhibits an increase in non-classical monocytes. As the Suzuki stage level increases, the proportions of plasmacytoid DCs and monocyte-derived DCs decrease. Furthermore, T cells, monocytes, DCs, and PMN-MDSCs in the early-stage MMD group show activation of the canonical NF-κB signaling pathway. We summarized and compared the similarities and differences between early-stage MMD patients and later-stage MMD patients. There is a potential role of circulating immune dysfunction and inflammatory responses in the onset and development of MMD. [ABSTRACT FROM AUTHOR]

Cerebral cavernous malformations (CCMs) refer to a common vascular abnormality that affects up to 0.5% of the population. A somatic gain-of-function mutation in MAP3K3 (p.I441M) was recently reported in sporadic CCMs, frequently accompanied by somatic activating PIK3CA mutations in diseased endothelium. However, the molecular mechanisms of these driver genes remain elusive. In this study, we performed whole-exome sequencing and droplet digital polymerase chain reaction to analyze CCM lesions and the matched blood from sporadic patients. 44 of 94 cases harbored mutations in KRIT1/CCM2 or MAP3K3, of which 75% were accompanied by PIK3CA mutations (P = 0.006). AAV-BR1-mediated brain endothelial-specific MAP3K3I441M overexpression induced CCM-like lesions throughout the brain and spinal cord in adolescent mice. Interestingly, over half of lesions disappeared at adulthood. Single-cell RNA sequencing found significant enrichment of the apoptosis pathway in a subset of brain endothelial cells in MAP3K3I441M mice compared to controls. We then demonstrated that MAP3K3I441M overexpression activated p38 signaling that is associated with the apoptosis of endothelial cells in vitro and in vivo. In contrast, the mice simultaneously overexpressing PIK3CA and MAP3K3 mutations had an increased number of CCM-like lesions and maintained these lesions for a longer time compared to those with only MAP3K3I441M. Further in vitro and in vivo experiments showed that activating PI3K signaling increased proliferation and alleviated apoptosis of endothelial cells. By using AAV-BR1, we found that MAP3K3I441M mutation can provoke CCM-like lesions in mice and the activation of PI3K signaling significantly enhances and maintains these lesions, providing a preclinical model for the further mechanistic and therapeutic study of CCMs. [ABSTRACT FROM AUTHOR]

We aimed to study the clinical and radiological characteristics of intracranial tumors and explore the possible predictive value of these characteristics in relation to perioperative outcomes in elderly patients. We retrospectively identified 1535 elderly patients (aged 65 years and older) with intracranial tumors who underwent surgical resection between 2014 and 2018 in Beijing Tiantan Hospital. Factors associated with an increased risk of unfavorable perioperative performance and complications were investigated. Meningiomas were the most common tumors in the cohort (43.26%). The overall risk of perioperative death was 0.59%, and 42.80% of patients were discharged with unfavorable performance (Karnofsky Performance Scale [KPS] score ≤ 70). Of all patients, 39.22% had one or more complications after surgical resection. Aggressive surgery significantly lowered the rate of unfavorable perioperative outcomes (P = 0.000) with no increase in postoperative complications (P = 0.153), but it failed to be an independent predictor for perioperative outcomes in the multivariate analysis. Low performance status at admission (KPS ≤ 70) was independently associated with both unfavorable perioperative performance (P = 0.000) and complications (P = 0.000). In addition to the histopathological patterns of tumors, low performance status at admission is an independent predictor for both unfavorable perioperative performance and the occurrence of complications in elderly patients with intracranial tumors who have undergone surgical resections. However, age is not associated with perioperative outcomes in elderly patients. [ABSTRACT FROM AUTHOR]