High glutamine increases stroke risk by inducing the endothelial-to-mesenchymal transition in moyamoya disease.

At present, there is limited research on the mechanisms underlying moyamoya disease (MMD). Herein, we aimed to determine the role of glutamine in MMD pathogenesis, and 360 adult patients were prospectively enrolled. Human brain microvascular endothelial cells (HBMECs) were subjected to Integrin Subunit Beta 4 (ITGB4) overexpression or knockdown and atorvastatin. We assessed factors associated with various signaling pathways in the context of the endothelial-to-mesenchymal transition (EndMT), and the expression level of related proteins was validated in the superficial temporal arteries of patients. We found glutamine levels were positively associated with a greater risk of stroke (OR = 1.599, p = 0.022). After treatment with glutamine, HBMECs exhibited enhanced proliferation, migration, and EndMT, all reversed by ITGB4 knockdown. In ITGB4-transfected HBMECs, the MAPK-ERK-TGF-ß/BMP pathway was activated, with Smad4 knockdown reversing the EndMT. Furthermore, atorvastatin suppressed the EndMT by inhibiting Smad1/5 phosphorylation and promoting Smad4 ubiquitination in ITGB4-transfected HBMECs. We also found the protein level of ITGB4 was upregulated in the superficial temporal arteries of patients with MMD. In conclusion, our study suggests that glutamine may be an independent risk factor for hemorrhage or infarction in patients with MMD and targeting ITGB4 could potentially be therapeutic approaches for MMD.

Glymphatic Impairment Associated with Neurocognitive Dysfunction in Moyamoya Disease.

Glymphatic system alterations have been proved to be associated with cognitive dysfunction in neurodegenerative diseases. The glymphatic pathway has not been elucidated in moyamoya disease (MMD), which was recognized as a chronic hypoperfusion model for neurodegenerative disease. Here, we aimed to investigate the glymphatic system activity and its relation with neurocognition, and associated hallmarks in MMD. We prospectively recruited 30 MMD patients and 30 matched healthy controls (HC). Participants underwent MRI and neurocognition evaluation. The glymphatic function was assessed by diffusion tensor image analysis along perivascular space (DTI-ALPS) index. Gray matter volume (GMV) and microstructural alterations were calculated. Neurodegenerative-related serum biomarkers were examined. The mediation effect of ALPS index in the associations between variables and neurocognition were further explored. A lower ALPS index was identified in patients with MMD (P < 0.001). The decreased ALPS index was significantly correlated with declined neurocognitive performance. Moreover, the reduced ALPS index was notably linked with lower total GMV% and deep GMV% (P < 0.01). Microstructural changes in the periventricular areas were detected and associated with ALPS index in MMD. Serum neurodegenerative biomarkers (ApoE, Aß40, Aß42, and Aß42/Aß40) were significantly elevated and related to ALPS index. Additionally, the ALPS index significantly mediated the associations of microstructural alterations and ApoE level with neurocognitive dysfunction. The ALPS index was notably lower MMD in patients, suggesting the utility as a marker of potential glymphatic dysfunction. The index acted as a significant mediator in neurocognitive dysfunction. These findings indicated that glymphatic impairment may interact with MMD-related pathophysiological processes.

Circulating immune cell landscape and T-cell abnormalities in patients with moyamoya disease.

BACKGROUND: Moyamoya disease (MMD) stands as a prominent cause of stroke among children and adolescents in East Asian populations. Although a growing body of evidence suggests that dysregulated inflammation and autoimmune responses might contribute to the development of MMD, a comprehensive and detailed understanding of the alterations in circulating immune cells associated with MMD remains elusive. METHODS: In this study, we employed a combination of single-cell RNA sequencing (scRNA-seq), mass cytometry and RNA-sequencing techniques to compare immune cell profiles in peripheral blood samples obtained from patients with MMD and age-matched healthy controls. RESULTS: Our investigation unveiled immune dysfunction in MMD patients, primarily characterized by perturbations in T-cell (TC) subpopulations, including a reduction in effector TCs and an increase in regulatory TCs (Tregs). Additionally, we observed diminished natural killer cells and dendritic cells alongside heightened B cells and monocytes in MMD patients. Notably, within the MMD group, there was an augmented proportion of fragile Tregs, whereas the stable Treg fraction decreased. MMD was also linked to heightened immune activation, as evidenced by elevated expression levels of HLA-DR and p-STAT3. CONCLUSIONS: Our findings offer a comprehensive view of the circulating immune cell landscape in MMD patients. Immune dysregulation in patients with MMD was characterized by alterations in T-cell populations, including a decrease in effector T-cells and an increase in regulatory T-cells (Tregs), suggest a potential role for disrupted circulating immunity in the aetiology of MMD.

Mass cytometry revealed the circulating immune cell landscape across different Suzuki stages of Moyamoya disease.

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.

Multiomics and blood-based biomarkers of moyamoya disease: protocol of Moyamoya Omics Atlas (MOYAOMICS).

BACKGROUND: Moyamoya disease (MMD) is a rare and complex cerebrovascular disorder characterized by the progressive narrowing of the internal carotid arteries and the formation of compensatory collateral vessels. The etiology of MMD remains enigmatic, making diagnosis and management challenging. The MOYAOMICS project was initiated to investigate the molecular underpinnings of MMD and explore potential diagnostic and therapeutic strategies. METHODS: The MOYAOMICS project employs a multidisciplinary approach, integrating various omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, to comprehensively examine the molecular signatures associated with MMD pathogenesis. Additionally, we will investigate the potential influence of gut microbiota and brain-gut peptides on MMD development, assessing their suitability as targets for therapeutic strategies and dietary interventions. Radiomics, a specialized field in medical imaging, is utilized to analyze neuroimaging data for early detection and characterization of MMD-related brain changes. Deep learning algorithms are employed to differentiate MMD from other conditions, automating the diagnostic process. We also employ single-cellomics and mass cytometry to precisely study cellular heterogeneity in peripheral blood samples from MMD patients. CONCLUSIONS: The MOYAOMICS project represents a significant step toward comprehending MMD's molecular underpinnings. This multidisciplinary approach has the potential to revolutionize early diagnosis, patient stratification, and the development of targeted therapies for MMD. The identification of blood-based biomarkers and the integration of multiple omics data are critical for improving the clinical management of MMD and enhancing patient outcomes for this complex disease.

Metabolic alterations of peripheral blood immune cells and heterogeneity of neutrophil in intracranial aneurysms patients.

BACKGROUND: Intracranial aneurysms (IAs) represent a severe cerebrovascular disease that can potentially lead to subarachnoid haemorrhage. Previous studies have demonstrated the involvement of peripheral immune cells in the formation and progression of IAs. Nevertheless, the impact of metabolic alterations in peripheral immune cells and changes in neutrophil heterogeneity on the occurrence and progression of IAs remains uncertain. METHODS: Single-cell Cytometry by Time-of-Flight (CyTOF) technology was employed to profile the single-cell atlas of peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) in 72 patients with IAs. In a matched cohort, metabolic shifts in PBMC subsets of IA patients were investigated by contrasting the expression levels of key metabolic enzymes with their respective counterparts in the healthy control group. Simultaneously, compositional differences in peripheral blood PMNs subsets between the two groups were analysed to explore the impact of altered heterogeneity in neutrophils on the initiation and progression of IAs. Furthermore, integrating immune features based on CyTOF analysis and clinical characteristics, we constructed an aneurysm occurrence model and an aneurysm growth model using the random forest method in conjunction with LASSO regression. RESULTS: Different subsets exhibited distinct metabolic characteristics. Overall, PBMCs from patients elevated CD98 expression and increased proliferation. Conversely, CD36 was up-regulated in T cells, B cells and monocytes from the controls but down-regulated in NK and NKT cells. The comparison also revealed differences in the metabolism and function of specific subsets between the two groups. In terms of PMNs, the neutrophil landscape within patients group revealed a pronounced shift towards heightened complexity. Various neutrophil subsets from the IA group generally exhibited lower expression levels of anti-inflammatory functional molecules (IL-4 and IL-10). By integrating clinical and immune features, the constructed aneurysm occurrence model could precisely identify patients with IAs with high prediction accuracy (AUC = 0.987). Furthermore, the aneurysm growth model also exhibited superiority over ELAPSS scores in predicting aneurysm growth (lower prediction errors and out-of-bag errors). CONCLUSION: These findings enhanced our understanding of peripheral immune cell participation in aneurysm formation and growth from the perspectives of immune metabolism and neutrophil heterogeneity. Moreover, the predictive model based on CyTOF features holds the potential to aid in diagnosing and monitoring the progression of human IAs.

Association of lysine pathway metabolites with moyamoya disease.

BACKGROUND AND OBJECTIVE: Lysine and its pathway metabolites have been identified as novel biomarkers for metabolic and vascular diseases. The role of them in the identification of moyamoya disease (MMD) has not been elucidated. This study aimed to determine the association between lysine pathway metabolites and the presence of MMD. METHODS: We prospectively enrolled 360 MMD patients and 89 healthy controls from September 2020 to December 2021 in Beijing Tiantan Hospital. Serum levels of lysine, pipecolic acid and 2-aminoadipic acid were measured by liquid chromatography-mass spectrometry. We employed logistic regression and restricted cubic spline to explore the association between these metabolites and the presence of MMD. Stratified analyses were also conducted to test the robustness of results. RESULTS: We observed that lysine levels in MMD patients were significantly higher and pipecolic acid levels were significantly lower compared to HCs (both p < 0.001), while no difference was found in the level of 2-AAA between both groups. When comparing metabolites by quartiles, elevated lysine levels were linked to increased odds for MMD (the fourth quartile [Q4] vs the first quartile [Q1]: odds ratio, 3.48, 95%CI [1.39-8.75]), while reduced pipecolic acid levels correlated with higher odds (Q4 vs Q1: odds ratio, 0.08; 95 % CI [0.03-0.20]). The restricted cubic spline found a L-shaped relationship between pipecolic acid level and the presence of MMD, with a cutoff point at 2.52 µmol/L. Robust results were also observed across subgroups. CONCLUSION: Elevated lysine levels were correlated with increased odds of MMD presence, while lower pipecolic acid levels were associated with higher odds of the condition. These results suggest potential new biomarkers for the identification of MMD. CLINICAL TRIAL REGISTRY NUMBER: URL: https://www.chictr.org.cn/. Unique identifier: ChiCTR2200061889.

The brain nebula: minimally invasive brain-computer interface by endovascular neural recording and stimulation.

A brain-computer interface (BCI) serves as a direct communication channel between brain activity and external devices, typically a computer or robotic limb. Advances in technology have led to the increasing use of intracranial electrical recording or stimulation in the treatment of conditions such as epilepsy, depression, and movement disorders. This indicates that BCIs can offer clinical neurological rehabilitation for patients with disabilities and functional impairments. They also provide a means to restore consciousness and functionality for patients with sequelae from major brain diseases. Whether invasive or non-invasive, the collected cortical or deep signals can be decoded and translated for communication. This review aims to provide an overview of the advantages of endovascular BCIs compared with conventional BCIs, along with insights into the specific anatomical regions under study. Given the rapid progress, we also provide updates on ongoing clinical trials and the prospects for current research involving endovascular electrodes.

Brain-computer interface digital prescription for neurological disorders.

Neurological and psychiatric diseases can lead to motor, language, emotional disorder, and cognitive, hearing or visual impairment By decoding the intention of the brain in real time, the Brain-computer interface (BCI) can first assist in the diagnosis of diseases, and can also compensate for its damaged function by directly interacting with the environment; In addition, provide output signals in various forms, such as actual motion, tactile or visual feedback, to assist in rehabilitation training; Further intervention in brain disorders is achieved by close-looped neural modulation. In this article, we envision the future BCI digital prescription system for patients with different functional disorders and discuss the key contents in the prescription the brain signals, coding and decoding protocols and interaction paradigms, and assistive technology. Then, we discuss the details that need to be specially included in the digital prescription for different intervention technologies. The third part summarizes previous examples of intervention, focusing on how to select appropriate interaction paradigms for patients with different functional impairments. For the last part, we discussed the indicators and influencing factors in evaluating the therapeutic effect of BCI as intervention.

Risk stratification of delayed causative aneurysm detection and long-term outcome in angiographically negative spontaneous subarachnoid haemorrhage.

BACKGROUND: The risk factors of aetiology and poor outcome in angiographically negative subarachnoid haemorrhage (anSAH) were unclearly. METHODS: The authors performed a retrospective review of a prospectively maintained database for anSAH patients between 2014 and 2018. AnSAH was defined as SAH presents in CT with no underlying vascular abnormality on initial digital subtraction angiography (DSA) within 72 hours of admission. Baseline and follow-up information, including medical history, bleeding pattern (perimesencephalic angiogram-negative SAH (PAN-SAH) and non-PAN-negative SAH (NPAN-SAH)), modified Fisher Scale (mFS), Glasgow Coma Score (GCS), Hunt-Hess grade, repeated imaging and causative vascular lesions and follow-up modified Rankin Scale (mRS) were reviewed. Poor outcome was defined as mRS scored 3-6 at last clinical follow-up. RESULTS: Among 303 enrolled patients, 272 patients underwent at least once repeated imaging examination (median follow-up time, 3.0 months). Twenty-one (7.7%) aneurysms were detected. Multivariate logistic analysis showed that NPAN-SAH and mFS 3-4 were associated with a high rate of aneurysm detection in anSAH patients. Based on risk stratification, the aneurysm detection rate in the high-risk group (both NPAN-SAH and mFS 3-4) was as high as 20.370 per 100 person-years. Furthermore, of 251 non-aneurysm anSAH patients, after a total follow-up time of 1265.83 patient-years, poor outcome occurred in 18 (7.2%) patients. Multivariate Cox analysis found that NPAN-SAH and GCS 3-12 were associated with a high rate of poor outcome of anSAH. The cumulative 5-year incidence rate for poor outcome in the non-aneurysm anSAH patients in the high-risk group (both NPAN-SAH and GCS 3-12) was as high as 75.302 per 100 person-years. CONCLUSIONS: Even in anSAH confirmed by initial DSA, patients with NPAN-SAH and mFS 3-4 should be monitored for delayed causative aneurysm detection, meanwhile in non-aneurysm anSAH patients, NPAN-SAH and initial functional impairment are associated with poor prognosis.

Effectiveness of indirect revascularization for adult hemorrhagic moyamoya disease: a 10-year follow-up study.

OBJECTIVE: The optimal surgical approach for hemorrhagic moyamoya disease (hMMD) continues to be a topic of debate. The authors' prior research demonstrated that both combined and indirect revascularization were efficacious. However, questions remain regarding the long-term prognosis consistency between these two treatments. Therefore, the objective of this study was to evaluate and compare the enduring effects of these surgical modalities on adult hMMD, extending the findings of the authors' previous studies. METHODS: The authors recruited patients diagnosed with hMMD between 2010 and 2015. The patients were categorized into two groups: those who underwent combined revascularization (superficial temporal artery-middle cerebral artery bypass alongside dural reverse application) and those who underwent indirect revascularization (encephaloduroarteriosynangiosis [EDAS]). The primary and secondary endpoints of this study were instances of rebleeding, confirmed with CT scan, and death resulting from rebleeding, respectively. The authors estimated rebleeding-free and death-free survival rates by utilizing the Kaplan-Meier survival method. They used Cox regression to adjust for confounders and to evaluate the effects of the varying surgical modalities on the endpoints. RESULTS: After an average follow-up period of 114 months, 35 patients (28.6%) experienced 40 rebleeding events, yielding an average annual incidence of 3.5%. Of the 79 patients who received combined revascularization, 17 (21.5%) experienced rebleeding events. Similarly, of 43 patients who underwent EDAS, 18 (41.9%) experienced rebleeding events (p = 0.018). Most rebleeding instances occurred 61-120 months after surgery (21 patients [60%]), followed by 12-60 months (11 patients [31.4%]). Multivariate survival analysis highlighted significant differences in surgical outcomes (HR 0.33, 95% CI 0.15-0.74, p = 0.007). The authors observed that 8 patients (10.1%) died of rebleeding events in the combined group, as well as 10 patients (23.3%) in the EDAS group. Despite the lack of a statistically significant difference in mortality (p = 0.051), multivariable survival analysis found a significant difference (HR 0.31, 95% CI 0.10-0.97, p = 0.044). CONCLUSIONS: High rebleeding rates persist in adult hMMD patients, even after revascularization. Combined revascularization proved superior to EDAS in preventing long-term rebleeding. In contrast, EDAS alone did not display a clear effect on reducing long-term rebleeding rates.

Zabramski classification in predicting the occurrence of symptomatic intracerebral hemorrhage in sporadic cerebral cavernous malformations.

OBJECTIVE: The authors aimed to investigate the evolutionary characteristics of the Zabramski classification of cerebral cavernous malformations (CCMs) and the value of the Zabramski classification in predicting clinical outcome in patients with sporadic CCM. METHODS: This retrospective study consecutively included cases of sporadic CCM that had been untreated from January 2001 through December 2021. Baseline and follow-up patient information was recorded. The evolution of the Zabramski classification of a sporadic CCM was defined as the initial lesion type changing into another type for the first time on MRI follow-up. The primary outcome was the occurrence of a hemorrhage event, which was defined as a symptomatic event with radiological evidence of overt intracerebral hemorrhage. RESULTS: Among the 255 included cases, 55 (21.6%) were classified as type I CCM, 129 (50.6%) as type II CCM, and 71 (27.8%) as type III CCM, based on initial MRI. During a mean follow-up of 58.8 ± 33.6 months, 51 (20.0%) patients had lesion classification transformation, whereas 204 (80.0%) patients maintained their initial type. Among the 51 transformed lesions, 29 (56.9%) were type I, 11 (21.6%) were type II, and 11 (21.6%) were type III. Based on all follow-up imaging, of the initial 55 type I lesions, 26 (47.3%) remained type I and 27 (49.1%) regressed to type III because of hematoma absorption; 91.5% of type II and 84.5% of type III lesions maintained their initial type during MRI follow-up. The classification change rate of type I lesions was statistically significantly higher than those of type II and III lesions. After a total follow-up of 1157.7 patient-years, new clinical hemorrhage events occurred in 40 (15.7%) patients. The annual cumulative incidence rate for symptomatic hemorrhage in all patients was 3.4 (95% CI 2.5-4.7) per 100 person-years. Kaplan-Meier survival analysis showed that the annual cumulative incidence rate for symptomatic hemorrhage of type I CCM (15.3 per 100 patient-years) was significantly higher than those of type II (0.6 per 100 patient-years) and type III (2.3 per 100 patient-years). CONCLUSIONS: This study suggests that the Zabramski classification is helpful in estimating clinical outcome and can assist with surgical decision-making in patients with sporadic CCM.

Single-Cell Atlas of Atherosclerosis Patients by Cytof: Circulatory and Local Immune Disorders.

Atherosclerosis (AS) is a common underlying pathology of coronary artery disease, peripheral artery disease, and stroke. The characteristics of immune cells within plaques and their functional relationships with blood are crucial in AS. In this study, Mass cytometry (CyTOF), RNA-sequencing and immunofluorescence were combined to comprehensively analyze plaque tissues and peripheral blood from 25 AS patients (22 for Mass cytometry and 3 for RNA-sequencing), as well as blood from 20 healthy individuals. The study identified a complexity of leukocytes in the plaque, including both defined anti-inflammatory and pro-inflammatory subsets such as M2-like CD163+ macrophages, Natural killer T cells (NKT), CD11b+ CD4+ T effector memory cells (Tem), and CD8+ terminally differentiated effector memory cells (TEMRA). Functionally activated cell subsets were also found in peripheral blood in AS patients, highlighting the vivid interactions between leukocytes in plaque and blood. The study provides an atlas of the immune landscape in atherosclerotic patients, where pro-inflammatory activation was found to be a major feature of peripheral blood. The study identified NKT, CD11b+ CD4+ Tem, CD8+ TEMRA and CD163+ macrophages as key players in the local immune environment.

Hybrid surgery can improve neurocognitive function in patients with internal carotid artery occlusion.

Internal carotid artery occlusion (ICAO) is a relatively uncommon but important cause of transient ischaemic attack and cerebral infarction. Hybrid surgery (HS) improves cerebral perfusion, but its impact on neurocognitive function has been controversial. Patients with symptomatic chronic ICAO treated by hybrid surgery or medical treatment from 2016 to 2019 were included. We recorded and analysed the clinical characteristics, angiographic data, outcomes and cognitive status. Functional assessments, including the National Institutes of Health Stroke Scale (NIHSS), the Barthel Index, and a battery of neuropsychological tests, including the Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale-Cognitive Subtest (ADAS-cog), verbal fluency, and Colour Trail test Parts 1 and 2, were administered. Significant improvements in the ADAS (before, 7.5 ± 6.2 versus after, 5.2 ± 5.7; P = 0.022), MMSE (before, 25.5 ± 2.8 versus after, 28.1 ± 2.3; P = 0.013), and Colour Trail test Part 1 (before, 118.3 ± 26.5 versus after, 96.2 ± 23.1; P = 0.016) were observed six months after HS. Moreover, the abovementioned postprocedure scales were ameliorated in the HS group. This study found that in patients with multiple symptomatic ICAO and objective ipsilateral ischaemia, successful HS leads to improvement in the scores of three cognitive tests.

Clinical neuromodulatory effects of deep brain stimulation in disorder of consciousness: A literature review.

BACKGROUND: The management of patients with disorders of consciousness (DOC) presents substantial challenges in clinical practice. Deep brain stimulation (DBS) has emerged as a potential therapeutic approach, but the lack of standardized regulatory parameters for DBS in DOC hinders definitive conclusions. OBJECTIVE: This comprehensive review aims to provide a detailed summary of the current issues concerning patient selection, target setting, and modulation parameters in clinical studies investigating the application of DBS for DOC patients. METHODS: A meticulous systematic analysis of the literatures was conducted, encompassing articles published from 1968 to April 2023, retrieved from reputable databases (PubMed, Embase, Medline, and Web of Science). RESULTS: The systematic analysis of 21 eligible articles, involving 146 patients with DOC resulting from acquired brain injury or other disorders, revealed significant insights. The most frequently targeted regions were the Centromedian-parafascicular complex (CM-pf) nuclei and central thalamus (CT), both recognized for their role in regulating consciousness. However, other targets have also been explored in different studies. The stimulation frequency was predominantly set at 25 or 100 Hz, with pulse width of 120 µs, and voltages ranged from 0 to 4 V. These parameters were customized based on individual patient responses and evaluations. The overall clinical efficacy rate in all included studies was 39.7%, indicating a positive effect of DBS in a subset of DOC patients. Nonetheless, the assessment methods, follow-up durations, and outcome measures varied across studies, potentially contributing to the variability in reported efficacy rates. CONCLUSION: Despite the challenges arising from the lack of standardized parameters, DBS shows promising potential as a therapeutic option for patients with DOC. However, there still remains the need for standardized protocols and assessment methods, which are crucial to deepen the understanding and optimizing the therapeutic potential of DBS in this specific patient population.

A novel system for evaluating collateralization of the external carotid artery after cerebral revascularization in moyamoya disease.

OBJECTIVE: The objective of this retrospective study was to establish a novel system for evaluating collateralization of the external carotid artery in patients with moyamoya disease (MMD) following direct and indirect revascularization surgeries. METHODS: The authors conducted a retrospective analysis of 456 patients diagnosed with MMD who underwent direct and indirect revascularization procedures at Beijing Tiantan Hospital, Capital Medical University, between January 2015 and May 2023. Using a newly proposed digital subtraction angiography (DSA)-based evaluation system, the authors assessed collateralization angiogenesis objectively and in a standardized manner. RESULTS: The authors' findings indicated that there was no significant difference in collateralization angiogenesis between patients undergoing direct or indirect cerebral revascularization (p = 0.702). However, after cerebral revascularization, patients with ischemic MMD exhibited significantly higher collateralization angiogenesis compared with those with hemorrhagic MMD (p = 0.007). Children with MMD demonstrated higher angiogenesis levels than adults (p < 0.001), but subgroup analysis showed age-specific variations. In adults, collateralization angiogenesis was significantly greater in those with ischemic MMD (p = 0.006), whereas in children, no significant difference was noted between ischemic and hemorrhagic MMD (p = 0.962). Furthermore, regardless of MMD type, direct and indirect revascularization methods yielded similar collateralization angiogenesis (p = 0.962 and p = 0.963, respectively). Importantly, the Matsushima grading system revealed significant differences in angiogenesis in patients with ischemic MMD (p < 0.001). CONCLUSIONS: The newly introduced DSA-based evaluation system offers an objective and standardized method for assessing collateralization angiogenesis in MMD. This study supports the efficacy of both direct and indirect revascularization surgical procedures and highlights distinct pathophysiological processes of ischemic and hemorrhagic disease subtypes. These findings contribute to a better understanding of surgical outcomes and aid in the selection of appropriate treatment strategies for patients with MMD.

Gut microbiota in adults with moyamoya disease: characteristics and biomarker identification.

Background and purpose: When it comes to the onset of moyamoya disease (MMD), environmental variables are crucial. Furthermore, there is confusion about the relationship between the gut microbiome, an environmental variable, and MMD. Consequently, to identify the particular bacteria that cause MMD, we examined the gut microbiome of MMD individuals and healthy controls (HC). Methods: A prospective case-control investigation was performed from June 2021 to May 2022. The fecal samples of patients with MMD and HC were obtained. Typically, 16S rRNA sequencing was employed to examine their gut microbiota. The QIIME and R softwares were used to examine the data. The linear discriminant analysis effect size analysis was used to determine biomarkers. Multivariate analysis by linear models (MaAsLin)2 were used to find associations between microbiome data and clinical variables. Model performance was assessed using the receiver operating characteristic curve and the decision curve analysis. Results: This investigation involved a total of 60 MMD patients and 60 HC. The MMD group's Shannon and Chao 1 indices were substantially lower than those of the HC cohort. ß-diversity was significantly different in the weighted UniFrac distances. At the phylum level, the relative abundance of Fusobacteriota/Actinobacteria was significantly higher/lower in the MMD group than that in the HC group. By MaAsLin2 analysis, the relative abundance of the 2 genera, Lachnoclostridium and Fusobacterium, increased in the MMD group, while the relative abundance of the 2 genera, Bifidobacterium and Enterobacter decreased in the MMD group. A predictive model was constructed by using these 4 genera. The area under the receiver operating characteristic curve was 0.921. The decision curve analysis indicated that the model had usefulness in clinical practice. Conclusions: The gut microbiota was altered in individuals with MMD, and was characterized by increased abundance of Lachnoclostridium and Fusobacterium and decreased abundance of Bifidobacterium and Enterobacter. These 4 genera could be used as biomarkers and predictors in clinical practice.

The association between hemoglobin concentration and clinical outcomes after aneurysmal subarachnoid hemorrhage: Insights from the LongTEAM registry.

OBJECTIVE: The aim of this study is to explore whether preoperative hemoglobin levels could serve as a prospective biomarker for early brain injury in patients with aneurysmal subarachnoid hemorrhage (aSAH). This investigation seeks to discern its association with postoperative complications and unfavorable clinical outcomes. METHODS: We conducted a comprehensive analysis of data derived from the LongTeam registry, including patients with aSAH diagnosed between January 2015 and September 2021. These patients were stratified into three distinct groups based on their hemoglobin levels: anemic, standard, and elevated HGB. We employed logistic models featuring spline transformations to assess the relationship between HGB levels and in-hospital complications. Furthermore, a multivariate Cox proportional hazard model was employed to estimate the impact of elevated hemoglobin levels on the hazard function, which was elucidated through Kaplan-Meier curves. RESULTS: Our study comprised a total of 988 patients, among whom 115 (11.6%) presented preoperative anemia, and 63 (6.4%) exhibited elevated preoperative HGB levels. Following adjustments for potential confounding factors, no significant disparity in risk was evident between anemic patients and those with standard HGB levels. However, individuals with elevated HGB levels displayed a heightened incidence and an increased risk of developing deep vein thrombosis (DVT, odds ratio [OR] = 2.39, 95% confidence interval [CI] = 1.16-4.91, p = 0.018; hazard ratio [HR] = 2.05, 95% CI 1.08-3.92, p = 0.015). Aberrant HGB concentrations did not demonstrate an association with other clinical outcomes. CONCLUSION: Our findings emphasize that abnormal HGB levels show no association with adverse outcomes at the 90 days mark after accounting for clinical confounding factors in patients with aSAH. Simultaneously, the study illuminates the potential of HGB as an early indicator for identifying patients at a heightened risk of developing DVT.