Xunsha Sun

Background Moyamoya disease (MMD), historically termed spontaneous occlusion of the circle of Willis, is a rare steno-occlusive cerebrovascular disease. Its etiology and pathogenesis remain incompletely understood, and lipid metabolism has recently attracted attention as a potential correlate of its clinical and biological heterogeneity. Methods This scoping review summarizes evidence on lipid metabolic abnormalities in MMD, including clinical associations, lipid-related markers, multi-omics findings, potential mechanisms, and therapeutic implications of lipid-modulating approaches. Results Epidemiological studies suggest that lipid abnormalities, including hypertriglyceridemia, low high-density lipoprotein cholesterol, and elevated lipoprotein(a), are common in MMD and are associated with disease phenotype, progression, stroke risk, and postoperative outcomes. Multi-omics studies reveal lipid metabolic alterations across peripheral blood, cerebrospinal fluid (CSF), and cerebrovascular tissue, suggesting a pattern of peripheral depletion, central enrichment, and tissue remodeling. Alterations in apolipoproteins such as APOE and lipid classes including sphingolipids, cardiolipins, and lysophosphatidylcholine may be associated with endothelial and vascular smooth muscle cell dysfunction, inflammatory responses, oxidative stress, and pathological vascular remodeling. Clinical studies suggest that statin use may be associated with improved collateral formation, although the underlying mechanisms remain uncertain. Conclusions This review maps emerging evidence linking lipid metabolism to MMD and highlights future directions for biomarker discovery, mechanistic validation, and therapeutic exploration.

Purpose: Surgical revascularization is the preferred treatment for most patients with Moyamoya disease (MMD). Nevertheless, a considerable number of eligible patients choose non-surgical management. This study aimed to identify factors influencing treatment decisions, with particular emphasis on asymptomatic MMD patients. Materials and Methods: We conducted a retrospective analysis of MMD patients without surgical contraindications treated at our center between 2010 and 2022. Baseline characteristics were compared using Wilcoxon rank-sum and chi-squared tests. Multivariable logistic regression was used to identify factors associated with treatment selection. Results: Among the 147 included patients, 62.6% underwent surgical treatment. Younger age (OR = 0.88, 95% CI: 0.88–0.94, p < 0.001), married status (OR = 653.3, 95% CI: 41.61–10,264.22, p < 0.001), and absence of hyperlipidemia (OR = 0.16, 95% CI: 0.03–0.85, p < 0.05) were significantly associated with choosing surgery. Asymptomatic patients underwent surgery at a higher rate than symptomatic patients (67.9% vs. 59.6%). Younger age was a significant predictor of surgical preference in both symptomatic and asymptomatic subgroups. Conclusion: Younger age is strongly associated with the choice of surgical treatment in MMD, including in asymptomatic cases.

Background: Mitochondrial D‐loop methylation leads to abnormal cerebral angiogenesis. This study examines its role in vascular phenotypes of moyamoya disease (MMD). Method: Blood samples from 96 intracranial artery stenosis/occlusion (ICASO) patients (35 MMD, 61 non‐MMD) and healthy controls underwent methylation analysis. D‐loop methylation levels were analyzed using chi‐square, T ‐test, and Wilcoxon tests. Propensity score matching (PSM) adjusted for age and gender disparities. Combine clinical information with methylation data to build a diagnostic model. Further studies included the methylation levels in MMD patients carrying the RNF213 p.R4810K mutation and the methylation levels and possible mechanisms of human brain microvascular endothelial cells (hCMEC/D3) with RNF213 knockdown. Results: Healthy controls showed higher D‐loop methylation than MMD ( p < 0.05). Post‐PSM, non‐MMD ICASO patients showed higher D‐loop methylation than MMD ( p < 0.05). The AUC of the prediction model was 0.891 (95% CI, 0.821–0.961) after combining clinical information with methylation data. MMD patients with the RNF213 mutation exhibited reduced methylation at most sites, though not statistically significant ( p > 0.05). RNF213 knockout in hCMEC/D3 enhanced proliferation, migration, and tube formation, while reducing apoptosis and DNMT1 expression, leading to decreased D‐loop methylation and ROS level, increased ATP production and mitochondrial membrane potential. Conclusion: There are differences in the methylation levels in the mitochondrial D‐loop region between MMD and non‐MMD ICASO. The methylation–metabolism–angiogenesis axis may represent a promising research direction for elucidating MMD pathogenesis.

Tracheostomy is frequently performed in severe ischemic stroke patients, yet the ideal timing for this procedure remains undefined. This study seeks to inform clinical decisions by evaluating the impact of early versus standard tracheostomy on clinical outcomes in this patient population. We retrospectively reviewed severe ischemic stroke patients who underwent tracheostomy at our hospital between January 2013 and November 2023. Patients were categorized into early tracheostomy (ET) and standard tracheostomy (ST) groups based on the interval from intubation to tracheostomy. Clinical outcomes were compared between the two groups. The logistic regression model was used to assess the correlation between the timing of tracheostomy and outcomes, and the Kaplan–Meier method was employed to analyze time-to-event results. The study encompassed 110 patients, with 57 in the ET group and 53 in the ST group. The results showed that the ET group had a longer interval from onset to intubation (P = 0.048), but there was no significant difference in the proportion of patients with severe disability after six months (OR 1.089 [95% CI 0.377–3.144], aOR 1.091 [95% CI 0.345–3.447]). The ET group demonstrated a shorter mechanical ventilation time (aOR 1.036 [95%CI 1.005–1.069]) and a decreased incidence of tracheostomy-related complications (aOR 5.378 [95%CI 1.065–27.144]). Early tracheostomy does not affect the long-term outcomes of patients with severe ischemic stroke, but it may offer potential benefits.

Objective: This study was aimed at evaluating the efficacy of the “zipper method,” a novel treatment strategy combining alternating plasma exchange (PLEX) and intravenous immunoglobulin (IVIG) pulse therapy, in adult patients with severe Guillain–Barré syndrome (GBS) requiring mechanical ventilation. Methods: A retrospective analysis was conducted on seven adult patients diagnosed with severe GBS and treated with mechanical ventilation from June 2022 to August 2023. Three received the “zipper method” (alternating PLEX and IVIG pulse therapy), and the other four were treated with the classic method (PLEX followed by IVIG pulse therapy). Clinical outcomes, including duration of continuous mechanical ventilation (CMV), length of stay (LOS) in the ICU, total hospital stay, muscle strength recovery as measured by the Muscle Research Council (MRC) score, and Guillain–Barré Syndrome Disability Scale (GBS‐DS) and days to unaided walking, were compared between the two groups. Results: The “zipper method” group exhibited significant improvements in clinical outcomes compared to the classic method group. Specifically, the duration of CMV was reduced to 17.67 days, the LOS in the ICU was 22.33 days, the mean days to hospital discharge were 40.67 days, and the MRC score at 1 month was 43.67 and at 2 months was 56.67. Furthermore, the GBS‐DS score at 2 months posttreatment was 1.00 and the mean days to unaided walking were 80.6 days, indicating a marked reduction in disability. Conclusion: The “zipper method” offers a promising new approach for the treatment of severe GBS in adults, leading to faster recovery of muscle strength and shorter ICU stays and length of hospital stay. This treatment strategy has the potential to improve patient outcomes and reduce the burden of severe GBS on healthcare systems. Further research, including prospective studies and randomized controlled trials, is warranted to validate these findings and explore the broader applicability of the “zipper method” in adult GBS treatment.

Moyamoya disease (MMD), most often diagnosed in children and adolescents, is a chronic cerebrovascular disease characterized by progressive stenosis at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Recently, many investigators show a great interest in MMD with pulmonary arterial hypertension (PAH). Ring finger protein 213 (RNF213) is a major susceptibility gene for MMD and also has strong correlations with PAH. Therefore, this review encapsulates current cases of MMD with PAH and discusses MMD with PAH in the aspects of epidemiology, pathology, possible pathogenesis, clinical manifestations, diagnosis, and treatment.

Background and purpose It remains inconclusive whether asymptomatic intracranial hemorrhage (aICH) after acute ischemic stroke is innocuous. We aimed to conduct a meta-analysis assessing the relationship between the aICH and poor neurological outcomes. Methods We searched PubMed, EMBASE and Web of Science from their inception to 30 November 2021 and performed a meta-analysis on the association between the aICH and neurological prognosis after acute ischemic stroke at 3 months, including poor outcomes (modified Rankin Scale [mRS] score ≥ 2 or mRS ≥ 3) and mortality. Results Fourteen studies were included in the analysis, reporting on a total of 10,915 participants after acute ischemic stroke. The risks of poor outcome (mRS ≥ 2 or mRS ≥ 3) in patients with aICH were significantly higher than patients without ICH (OR 1.70, 95% CI 1.33–2.18; OR 1.43, 95% CI 1.20–1.70, respectively), based on adjusted data. The difference between the two groups was not significant for mortality. The results of subgroup analysis showed aICH were associated with higher ratio of mild poor prognosis (mRS ≥ 2) (OR 1.59, 95% CI 1.11–2.27), but it had no association with functional dependence (mRS ≥ 3) after recanalization. No significant influence of aICH on poor outcome (mRS ≥ 3) was found in non-recanalization group. Further stratified analysis revealed that only aICH with patients receiving endovascular therapy (EVT) could increase the risk of mild poor prognosis (mRS ≥ 2) at 3 months. Conclusions Our results indicate that compared with patients without ICH, those who developed aICH during the acute stage of ischemic stroke had an increasing risk of worse outcome, especially in patients with endovascular therapy.

Although familial forms of cerebral cavernous malformation are mainly attributed to three CCM genes (KRIT1, CCM2 and PDCD10), no mutation is identified in sporadic cerebral cavernous malformation cases with a unique lesion, indicating additional genes for sporadic cerebral cavernous malformation. To screen the candidate genes, we conducted whole exome sequencing in 31 sporadic cerebral cavernous malformation patients and 32 healthy controls, and identified 5 affected individuals carrying 6 heterozygous deleterious mutations in RNF213 but no RNF213 mutation in healthy individuals. To further confirm RNF213 was associated with cerebral cavernous malformation, we generated rnf213a homozygous knockout zebrafish and found mutation of rnf213a in zebrafish led to a mulberry-like cluster of disordered-flow vascular channels which was reminiscent of human cerebral cavernous malformation. In addition, we revealed kbtbd7 and anxa6 were significantly downregulated due to rnf213a mutation through transcriptomic sequencing and RT-qPCR analysis. Based on the mulberry-like phenotype partly rescued by mRNA of kbtbd7 as well as anxa6, we suggested that rnf213a promoted mulberry-like cluster via downregulation of kbtbd7 and anxa6. Altogether, we firstly demonstrate RNF213is a novel candidate gene for sporadic cerebral cavernous malformation and the mutation of rnf213a is responsible for the mulberry-like cluster in zebrafish.