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.

Association of low-level blood lead with plasma homocysteine in US children and adolescents.

Although research in adults has revealed a positive relationship between blood lead levels (BLLs) and homocysteine (Hcy) levels in adults, few studies have investigated this relationship in children and adolescents. We evaluated the relationship between lowlevel blood lead and Hcy levels in US children and adolescents. A total of 8,313 children and adolescents aged 8-19 participated in this study via the National Health and Nutrition Examination Survey 1999-2006. Multivariable linear regression analyses were performed to examine the association between continuous BLLs and Hcy levels. The dose-dependent relationship between continuous BLLs and Hcy levels was analyzed using smooth curve fitting. The average age of participants was 14.1 ± 3.3 years (50.3% male). The mean values of BLLs and Hcy levels were 1.45 µg/dL and 5.77 µmol/L, respectively. In a multivariable adjusted model, an increase in 1.0 µg/dL of BLLs was associated with an elevation of 0.06 µmol/L in Hcy levels (ß = 0.06, 95%CI:0.02-0.10, P = 0.001). A linear relationship between BLLs and Hcy levels was discovered using smooth curve fitting (P non-linearity = 0.464). The relationship between low-level blood lead and Hcy levels was stronger on participants with lower serum folate levels (P for interaction = 0.002). Low BLLs were positively associated with plasma Hcy levels in children and adolescents, which varies depending on the levels of folate, vitamin B, and dietary supplements involved in Hcy metabolism.

Nonhematogenic circulating aneuploid cells confer inferior prognosis and therapeutic resistance in gliomas.

Aneuploidy is the hallmark of malignancy. Our previous study successfully detected nonhematogenic circulating aneuploidy cells (CACs) in types of gliomas. The current prospective clinical study aims to further precisely subcategorize aneuploid CACs, including CD31- circulating tumor cells (CTCs) and CD31+ circulating tumor endothelial cells, and thoroughly investigate the clinical utilities of these different subtypes of cells. Co-detection and analysis of CTCs and circulating tumor-derived endothelial cells (CTECs) expressing CD133, glial fibrillary acidic protein (GFAP), or epidermal growth factor receptor variant III (EGFR vIII) were performed by integrated subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) in 111 preoperative primary diffuse glioma patients. Aneuploid CACs could be detected in most de novo glioma patients. Among detected CACs, 45.6% were CD31- /CD45- aneuploid CTCs and the remaining 54.4% were CD31+ /CD45- aneuploid CTECs. Positive detection of CTECs significantly correlated with disruption of the blood-brain barrier. The median number of large CTCs (L CTCs, >5 µm, 2) in low-grade glioma (WHO grade 2) was less than high-grade glioma (WHO grades 3 and 4) (3, p = 0.044), but this difference was not observed in small CTCs (S CTCs, ≤5 µm), CTECs or CACs (CTCs + CTECs). The numbers of CTCs, CTECs, or CACs in patients with contrast-enhancing (CE) lesions considerably exceeded that of non-CE lesions (p < 0.05). Receiver operating characteristic curves demonstrated that CD31+ CTECs, especially L CTECs, exhibited a close positive relationship with CE lesions. Survival analysis revealed that the high number of CD31- CTCs could be an adverse factor for compromised progression-free survival and overall survival. Longitudinal surveillance of CD31- CTCs was suitable for evaluating the therapeutic response and for monitoring potential emerging treatment resistance.

Association between hyperhomocysteinaemia and the risk of all-cause and cause-specific mortality among adults in the USA.

Hyperhomocysteinaemia (HHcy) is associated with all-cause mortality in some disease states. However, the correlation between HHcy and the risk of mortality in the general population has rarely been researched. We aimed to evaluate the association between HHcy and all-cause and cause-specific mortality among adults in the USA. This study analysed data from the National Health and Nutrition Examination Survey database (1999-2002 survey cycle). A multivariable Cox regression model was built to evaluate the correlation between HHcy and all-cause and cause-specific mortality. Smooth curve fitting was used to analyse their dose-dependent relationship. A total of 8442 adults aged 18-70 years were included in this study. After a median follow-up period of 14·7 years, 1007 (11·9 %) deaths occurred including 197 CVD-related deaths, 255 cancer-related deaths and fifty-eight respiratory disease deaths. The participants with HHcy had a 93 % increased risk of all-cause mortality (hazard ratio (HR) 1·93; 95 % CI (1·48, 2·51)), 160 % increased risk of CVD mortality (HR 2·60; 95 % CI (1·52, 4·45)) and 82 % increased risk of cancer mortality (HR 1·82; 95 % CI (1·03, 3·21)) compared with those without HHcy. For unmeasured confounding, E-value analysis proved to be robust. In conclusion, HHcy was associated with high risk of all-cause and cause-specific (CVD, cancer) mortality among adults aged below 70 years.

Association of Homocysteine and Insulin Resistance with Increased Risk of Mortality in a Nondiabetic Population: Third National Health and Nutrition Examination Survey.

Background and Objective: The combined effect of insulin resistance (IR) and total plasma homocysteine (tHcy) levels on the risk of mortality in nondiabetic populations has rarely been studied. We aimed to examine the association of tHcy levels and IR with the risk of mortality in nondiabetic populations. Methods: This observational cohort study was based on data from the Third National Health and Nutrition Examination Survey (NHANES III) database (1999-2002). A generalized additive model based on the Cox proportional hazards models was applied to estimate the relationship of tHcy levels with all-cause and cardiovascular disease (CVD) mortality. Smooth curve fitting was used to analyze their dose-dependent relationship. Results: During 5.7 years of follow-up, a total of 146 (5.8%) deaths occurred, including 65 deaths from CVD among 2053 individuals aged 40-80 years. In the multivariable adjusted model, every 1-µM increment of the tHcy level was associated with a 15% increase in risk of all-cause mortality and 20% increase in risk of CVD mortality among participants with IR (adjusted HR [95% CI]: 1.15 [1.06-1.24] and 1.20 [1.04-1.38]). However, among participants without IR, an increase of 1 µM in the tHcy level was associated with a 6% increase in risk of all-cause mortality and 3% increase in risk of CVD mortality (adjusted HR [95% CI]: 1.06 [1.00-1.13] and 1.03 [0.92-1.16]). Conclusions: Homocysteine levels were associated with higher risk of all-cause and CVD mortality among individuals with IR than among those without IR in a nondiabetic population aged 40-80 years.

Ventriculoperitoneal Shunt Alone for Cerebrospinal Fluid Rhinorrhea With Neuroendocrine Alterations in Idiopathic Intracranial Hypertension: A Case Report and Literature Review.

Spontaneous skull base cerebrospinal fluid (CSF) leaks due to idiopathic intracranial hypertension (IIH) are a rare entity. Patients often present with CSF rhinorrhea, recurrent meningitis, chronic headache, and visual defects, while few patients have been reported to present with neuroendocrine alterations. Endonasal endoscopic repair is the first-line treatment for these leaks at present. However, the relatively high risk of recurrence remains the main cause of reoperation because of elevated intracranial pressure (ICP) after endoscopic surgery and absence of postoperative ICP management. A shunting procedure may stop CSF leakage or relieve symptoms in complex cases, and this is presently well-known as the last-line therapy for CSF liquorrhea. We describe a 29-year-old woman with spontaneous CSF rhinorrhea and neuroendocrine alterations due to IIH, and with no previous history of trauma, tumor, or nasal surgery. The bone defect in the skull base became implicated when the site of the leak was detected by cranial magnetic resonance imaging and computed tomography (CT). The patient was successfully managed via ventriculoperitoneal shunt (VPS) alone without endoscopic repair, and neuroendocrine alterations resolved after the shunting procedure.

The interaction of hypertension and homocysteine increases the risk of mortality among middle-aged and older population in the United States.

OBJECTIVES: To investigate the interaction of hypertension and total plasma homocysteine (tHcy) levels on risk of all-cause and cardiovascular disease (CVD) mortality among middle-aged and older population. METHODS: This observational cohort study analyzed data from the National Health and Nutrition Examination Survey database (1999-2002 survey cycle). A generalized additive model (GAM) based on Cox proportional hazards models was applied to estimate the relationship of tHcy level with all-cause and CVD mortality. Stratification analyses by sex and renal function were performed. RESULTS: Among 5724 individuals aged 40-85, 704 (12.3%) died, with 339 CVD deaths after a median follow-up period of 5.58 years. Mean age was 60.7 ±â€Š13.4 years (49.6% men). In the fully adjusted model, we found that per 1 µmol/l increment of plasma tHcy was associated with 8% increased risk of all-cause mortality and 7% increased risk of CVD mortality in hypertensive participants. The adjusted hazard ratio (95% CIs) for all-cause and CVD mortality were 1.08 (1.06-1.10) and 1.07 (1.04-1.10), respectively. There were pronounced interactive effects between hypertension and tHcy levels on risk of all-cause mortality (P for interaction = 0.031). CONCLUSION: Hypertension and tHcy levels can interactively affect the risk of all-cause mortality among middle-aged and older population. Conceivably, hypertension may further enhance the ability of elevated tHcy to provoke the risk of all-cause mortality.

Severe contralateral carotid stenosis or occlusion drive 30-day risk after carotid endarterectomy.

OBJECTIVES: The significant effects on the treatment of severe carotid stenosis by carotid endarterectomy have been widely recognized. However, it is controversial whether patients with severe contralateral carotid stenosis or occlusion (SCSO) can benefit from carotid endarterectomy surgery. This study aimed to estimate the SCSO effects on early outcomes after carotid endarterectomy with selective shunting. METHODS: Between August 2011 and October 2019, a total of 617 patients who underwent carotid endarterectomy with selective shunting were analyzed. SCSO was defined as >70% luminal narrowing of the contralateral extracranial carotid stenosis or occlusion. Of these patients, 116 were categorized into an SCSO group while the rest were assigned to the non-SCSO group. Primary study outcomes were the occurrence of major adverse events, defined as stroke, all-cause mortality, and myocardial infarction during the perioperative period after carotid endarterectomy. Traditional multivariable logistic regression model and logistic regression model adjusted for propensity scores were used to estimate the SCSO effects on primary outcomes. Interaction and stratified analyses were conducted according to age, sex, comorbidities (hypertension, diabetes), preoperative neurological deficit, preoperative symptoms, and shunt use. RESULTS: Mean age was 68.5 ± 9.2 years (86.1% men). Overall major adverse events rate within 30 days was 2.5%. Major adverse events rates in SCSO and non-SCSO groups were 9.5% and 1.6%, respectively. This difference was statistically significant (p < 0.001). In multivariable regression analysis, patients with SCSO had a higher risk of major adverse events (non-SCSO vs. SCSO: aOR 5.05 [95% CI, 1.78-14.55]). In 342 propensity score matched patients, results were consistent (propensity score: aOR, 3.78 [95% CI, 1.13-12.64]). CONCLUSIONS: SCSO is an independent predictor of 30-day major adverse events. Whether these patients with SCSO are suitable for carotid endarterectomy should be carefully considered.

Association of hypocalcemia with in-hospital mortality in critically ill patients with intracerebral hemorrhage: A retrospective cohort study.

Background and purpose: There was little evidence to study the relationship between hypocalcemia and mortality among critically ill patients with intracerebral hemorrhage (ICH) aged ≥16 years. This study aimed to determine the potential association between hypocalcemia and in-hospital and ICU mortality in patients with ICH in the United States. Methods: We analyzed 1,954 patients with ICH from the e-Intensive Care Unit Collaborative Research Database and divided them into hypocalcemia and non-hypocalcemia groups. Hypocalcemia was defined as albumin-adjusted total calcium below 8.4 mg/dl. The primary and secondary outcomes were hospital and ICU mortality, respectively. We performed multivariable regression and subgroup analyses to evaluate the association of hypocalcemia with hospital and ICU mortality. Cumulative survival rate analysis was performed using Kaplan-Meier curves with log-rank statistics. Results: We enrolled 1,954 patients with ICH who had been hospitalized in ICU for >24 h and were older than 16 years (average age, 61.8 years; men, 56.7%). We noted that 373 (19%) hospital mortality occurred, including 235 (12%) ICU mortality. In this sample, 195 patients had hypocalcemia. Multivariable logistic regression analyses showed that hypocalcemia was associated with a 67% increased risk of in-hospital and a 72% increased risk of ICU mortality. This association was consistent across subgroup analyses. Conclusions: Hypocalcemia was associated with a high risk of hospital and ICU mortality among critically ill patients with ICH. Future prospective, randomized, controlled studies are needed to confirm our results.

Role of circulating tumor cell detection in differentiating tumor recurrence from treatment necrosis of brain gliomas.

Differentiating treatment necrosis from tumor recurrence poses a diagnostic conundrum for many clinicians in neuro-oncology. To investigate the potential role of circulating tumor cells (CTCs) detection in differentiating tumor recurrence and treatment necrosis in brain gliomas, we retrospectively analyzed the data of 22 consecutive patients with tumor totally removed and new enhancing mass lesion(s) showed on MRI after initial radiotherapy. The 22 patients were finally classified into tumor recurrence group (n = 10) and treatment necrosis group (n = 12), according to evidence from the clinical course (n = 11) and histological confirmation (n = 11). All 22 patients received CTCs detection, and DSC-MRP and 11C-MET-PET were performed on 20 patients (90.9%) and 17patients (77.3%) respectively. The data of the diagnosis efficacy to differentiate the two lesions by CTC detection, MPR and PET were analyzed by ROC analysis. The mean CTCs counts were significantly higher in the tumor recurrence group (6.10 ± 3.28) compared to the treatment necrosis group (1.08 ± 2.54, p < 0.001). The ROC curve showed that an optimized cell count threshold of 2 had 100% sensitivity and 91.2% specificity with AUC = 0.933 to declare tumor recurrence. The diagnostic efficacy of CTC detection was superior to rCBV of DSC-MRP and rSUVmax in MET-PET. Furthermore, we observed that CTCs detection could have a potential role in predicting tumor recurrence in one patient. Our research results preliminarily showed the potential value of CTC detection in differentiating treatment necrosis from tumor recurrence in brain gliomas, and is worthy of further confirmation with large samples involved.

Poor Neurological Deficit Was an Independent 30-day Risk Factor in Symptomatic Carotid Stenosis after CEA with Selective Shunting.

BACKGROUND: Carotid endarterectomy (CEA) prevents the occurrence of stroke in the future, although its efficacy depends on the detection and control of high perioperative risk factors. We aimed to analyze the association between preoperative neurological deficit and the 30-day risk of major adverse cardiovascular events (MACEs) in CEA with selective shunting for symptomatic carotid stenosis. METHODS: We assessed 653 patients who underwent CEA with selective shunting for symptomatic carotid stenosis between August 2011 and August 2019. The primary outcomes of the study were the occurrence of MACEs, defined as stroke (ischemic stroke or cerebral hemorrhage), all-cause mortality, and myocardial infarction during the perioperative period after CEA. Baseline patient characteristics were analyzed to identify factors associated with perioperative (<30 days) MACEs. Multivariable logistic regression models were used to estimate the association between preoperative modified Rankin Scale (mRS) and the 30-day risk of MACEs. Interaction and stratified analyses were conducted according to age, drinking, history of hypertension and coronary artery disease, and surgical side. RESULTS: The mean age of patients was 68.7 ± 9.1 years, and 86.4% were men. The 30-day MACEs rate was 2.5%. In univariate logistic regression, histories of coronary artery disease (odds ratio (OR), 2.57 [95% confidence interval (CI), 1.04-6.34]), a severe contralateral carotid stenosis or occlusion (OR, 4.52 [95% CI, 1.84-11.11]), and a poor neurological deficit (mRS ≥ 3 versus mRS < 3: OR, 3.78 [95% CI, 1.21-11.82]) were associated with higher primary outcome rates. A history of hypertension did not increase the risk of MACEs (OR, 0.37 [95% CI, 0.15-0.89]). In the multivariable regression analysis, poor neurological deficit was associated with a higher risk of the MACEs within 30 days (mRS ≥ 3 versus mRS < 3: 11.1% vs. 2.0%, adjusted OR 5.70 [95% CI, 1.50-21.60]). The interaction analysis revealed no interactive role in the association between neurological deficit and 30-day risk of MACEs. CONCLUSIONS: Poor neurological deficit was an independent risk factor associated with the 30-day risk of MACEs in symptomatic patients who underwent CEA with selective shunting. Our findings may provide guidance to surgeons when treating patients with poor neurological deficit. The decision to perform surgery should be made after careful consideration.

A Feasibility Study of Low Cement Content Foamed Concrete Using High Volume of Waste Lime Mud and Fly Ash for Road Embankment.

This paper aims to study the feasibility of low cement content foamed concrete using waste lime mud (LM) and fly ash (FA) as mineral additives. The LM/FA ratio was first optimized based on the compressive strength. Isothermal calorimetry test, ESEM, and XRD were used to investigate the role of LM during hydration. Afterward, the optimized LM/FA ratio (1/5) was used to design foamed concrete with various wet densities (600, 700, 800 and 900 kg/m3) and LM-FA dosages (0%, 50%, 60%, 70% and 80%). Flowability measurements and mechanical measurements including compressive strength, flexural strength, splitting strength, elastic modulus, and California bearing ratio were conducted. The results show that the foamed concretes have excellent workability and stability with flowability within 170 and 190 mm. The high alkalinity of LM accelerated the hydration of FA, thereby increasing the early strength. The significant power functions were fitted for the relationships between flexural/splitting and compressive strength with all correlation coefficients (R2) larger with 0.95. The mechanical properties of the foamed concrete increased with the density increasing or LM-FA dosage decreasing. The compressive strength, tensile strength, CBR of all prepared foamed concretes were higher than the minimum requirements of 0.8 and 0.15 MPa and 8%, respectively in the standard.

Efficacy and Safety of Gamma Knife Radiosurgery for Meningiomas in Patients with Neurofibromatosis Type 2: A Long-Term Follow-Up Single-Center Study.

OBJECTIVE: To explore the efficacy and safety of Gamma Knife radiosurgery (GKRS) for meningiomas in patients with neurofibromatosis type 2 (NF2). METHODS: A series of 35 consecutive patients with 99 meningiomas in our department were retrospectively included from January 2000 to December 2015. Clinical records, magnetic resonance images, and follow-up data were reviewed. RESULTS: A total of 35 patients (25 women and 10 men) with 99 NF2-associated meningiomas were identified. All patients initially received GKRS. The patients' median age at the time of GKRS was 40 years (range, 16-61 years). The median prescription dose at the tumor margin was 13 Gy (range, 12-15 Gy). The median follow-up time was 96 months (range, 25-224 months). Twenty-nine patients received GKRS only once, and 6 patients received it multiple times. Six patients (17.1%) had radiation-related complications 7.5 ± 2.4 months after GKRS. Local control rates at 1, 3, and 5 years were 100%, 97.1%, and 90.6%, respectively. Distant control rates at 1, 3, and 5 years were 88.5%, 55.9%, and 45.5%, respectively. Five patients died of concomitant neurologic symptoms. No malignant transformation was observed during the follow-up periods in all 35 patients. CONCLUSIONS: GKRS represents an effective and safe management strategy with minimal invasion for patients with NF2-associated meningiomas. Our data showed a high local control rate of NF2-associated meningiomas by GKRS; however, the distant control rate is low, especially in young patients. For these patients, retreatment with GKRS may still be the advisable method.

Comparison of phenotypic markers and neural differentiation potential of human bone marrow stromal cells from the cranial bone and iliac crest.

Cellular therapies represent a new frontier in the treatment of neurological diseases. Accumulating evidence from preclinical studies of animal models suggests that mesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, are an effective therapy for neurological diseases. In this study, we established human MSC lines from both cranial bone marrow (cBMMSCs) and iliac crest bone marrow (iBMMSCs) from the same donors and found that cBMMSCs show higher expression of neural crest-associated genes than iBMMSCs. Moreover, as observed in both mRNA and protein assays, neurogenic-induced cells from cBMMSCs expressed significantly higher levels of neural markers, such as NESTIN, SLUG, SOX9, and TWIST, than those from iBMMSCs. Thus, cBMMSCs showed a greater tendency than iBMMSCs to differentiate into neuron-like cells.

Direct versus indirect bypasses for adult ischemic-type moyamoya disease: a propensity score-matched analysis.

OBJECTIVE The optimal surgical modality for moyamoya disease (MMD) remains unclear. The aim of this study was to compare the surgical effects of direct bypass (DB) and indirect bypass (IB) in the treatment of adult ischemic-type MMD. METHODS Adult patients with ischemic-type MMD who underwent either DB or IB from 2009 to 2015 were identified retrospectively from a prospective database. Patients lost to follow-up or with a follow-up period less than 12 months were excluded. Recurrent stroke events and modified Rankin Scale (mRS) scores at the last follow-up were compared between the 2 surgical groups after 1:1 propensity score matching. RESULTS A total of 220 patients were considered, including 143 patients who underwent DB and 77 patients who underwent IB. After propensity score matching, 70 pairs were obtained. The median follow-up period was 40.5 months (range 14-75 months) in the DB group and 31.5 months (range 14-71 months) in the IB group (p = 0.004). Kaplan-Meier analysis showed that patients who received DB had a longer stroke-free time (mean 72.1 months) compared with patients who received IB (mean 61.0 months) (p = 0.045). Good neurological status (mRS score ≤ 2) was achieved in 64 patients in the DB group (91.4%) and 66 patients in the IB group (94.3%), but there was no significant difference (p = 0.512). CONCLUSIONS Although neurological function outcome was not determined by the surgical modality, DB is more effective in preventing recurrent ischemic strokes than IB for adult ischemic-type MMD.

Effects of different surgical modalities on the clinical outcome of patients with moyamoya disease: a prospective cohort study.

OBJECTIVE Bypass surgery is the most common treatment for moyamoya disease (MMD), but there is controversy over which surgical modality is best. The objective of this study was to evaluate the clinical outcome of patients with MMD after undergoing different surgical modalities. METHODS A series of 696 consecutive MMD patients treated between June 2009 and May 2015 were screened in this prospective cohort study. Patients who did not undergo revascularization surgeries and those who underwent different surgical modalities in bilateral hemispheres were excluded. Finally, 529 patients who were observed for at least 12 months were included: 438 patients underwent unilateral surgery, and 91 patients underwent bilateral surgery. Of these, 241 patients underwent direct bypass (DB); 81, a combined bypass (CB); and 207, an indirect bypass (IB). Three clinical outcomes were evaluated and compared between surgical groups: recurrent stroke events, modified Rankin Scale (mRS) scores, and change in the main symptoms. RESULTS The mean follow-up period was 40 months. During the follow-up period, recurrent stroke was observed in 43 patients, including 15 patients with hemorrhage, 26 patients with ischemia (transient ischemic attack in 19 patients and infarction in 7 patients), and 2 patients with both hemorrhage and cerebral infarction. Kaplan-Meier analysis showed that patients who underwent a CB or DB had a longer ischemia-free time than those who underwent IB (p = 0.013); however, there was no significant difference in the hemorrhage-free time between the different surgical modalities (p = 0.534). A good neurological status (mRS score ≤ 2) was achieved in 495 patients (93.6%) and was significantly achieved by more children (98.2%) than adults (92.3%; p = 0.022). Surgical modalities were not significantly associated with outcome neurological status (p = 0.860). Moreover, improvement in symptoms was observed in 449 patients (84.9%) and was also significantly more common in children (93.0%) than in adults (82.7%; p = 0.006). No significant difference was observed between the different surgical modalities (p = 0.548). CONCLUSIONS CB and DB are more effective at preventing recurrent ischemic strokes than IB. However, there is no evidence that these 3 surgical modalities demonstrate significant differences in preventing recurrent hemorrhage.

Altered expression of circular RNAs in Moyamoya disease.

Moyamoya disease (MMD) is the most common pediatric cerebrovascular disease in Eastern Asian countries but the etiology is not well understood. Circular RNAs (circRNAs) have been implicated in various biological processes, but their role in the development of MMD remains unclear. To address this issue, we carried out a comparative circRNA microarray analysis of blood samples obtained from patients with MMD and healthy subjects and identified 146 circRNAs that were differentially expressed between the two groups. Of these, 29 were upregulated and 117 were downregulated in patients as compared to controls (fold change ≥2.0 and P<0.05). The microarray results were validated by quantitative reverse-transcription PCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that the differentially expressed circRNAs were primarily involved in angiogenesis, metabolism, and immune responses in MMD. In addition, the mitogen-activated protein kinase signaling pathway was found to be the core regulatory pathway associated with disease pathogenesis. These results indicate that specific circRNAs are aberrantly expressed in MMD and are potential therapeutic targets for its treatment.

Results of Conservative Follow-up or Surgical Treatment of Moyamoya Patients Who Present without Hemorrhage, Transient Ischemic Attack, or Stroke.

OBJECTIVE: The epidemiology of asymptomatic moyamoya disease (MMD) is still unclear, and the best management remains controversial. The aim of this study is to evaluate the prognosis of these patients with different management, conservative follow-up, or surgical treatment. METHODS: This prospective cohort study screened a series of 696 consecutive MMD patients from 2009-2015. Patients with any episodes of hemorrhage and ischemic stroke or TIA were excluded. Finally, 61 patients who were followed up for at least 12 months were included, with 52 patients who underwent surgical treatment and 9 patients who underwent conservative follow-up. Patients were divided into 2 groups: surgical and conservative. Advert events including newly hemorrhage and ischemic stroke and death were compared between the groups. Relationships between disease progression and collaterals and cerebral blood flow were analyzed separately. RESULTS: The mean follow-up period was 56.32 months (range, 11.3-112.62 months). During the follow-up period, 3 patients had symptomatic progression in the conservative group, 1 suffered a hemorrhage, and 2 had TIAs. Among the patients in the surgical group, 6 of them experienced TIAs. Kaplan-Meier analysis showed that patients receiving surgeries had a longer symptom-free time compared with patients in the conservative group (P = 0.015). Decreased cerebral blood flow had no influence on disease progression in patients in both groups. Existence of extracranial to intracranial collaterals showed a better outcome for patients in the surgical group but not the conservative group. CONCLUSIONS: Surgical treatment may be a better choice for patients with asymptomatic MMD. And patients with better collateral circulations, especially extracranial to intracranial collateral arteries, may have a better prognosis.

Adolescents with moyamoya disease: clinical features, surgical treatment and long-term outcomes.

BACKGROUND: This study aimed to elucidate the clinical features, surgical treatment and long-term outcomes of adolescent patients with moyamoya disease. METHODS: We reviewed consecutive patients with moyamoya vasculopathy who were admitted to our hospital from 2009 to 2015 to identify adolescent patients with moyamoya disease. Clinical features, surgical treatment and long-term outcomes were analyzed. Follow-up was performed by face-to-face or structured telephone interviews. Outcome measures were future stroke events. We performed univariate and multivariate time-to-event analyses to identify risk factors associated with future stroke events. RESULTS: A total of 95 adolescent patients with moyamoya disease (age at onset, 13.1 ± 2.3 years) were included in this study. During follow-up, 12 patients (12.6%) had stroke events. We found that the patients who underwent direct/combined bypass had a significantly lower risk of future strokes [hazard ratio (HR), 0.16; 95% confidence interval (CI), 0.03-0.74; P = 0.019] compared to patients who underwent indirect bypass. CONCLUSIONS: Our results demonstrate that direct/combined bypass can be more effective in preventing future strokes than indirect bypass in adolescent patients with moyamoya disease.

Ischemic Stroke in Young Adults with Moyamoya Disease: Prognostic Factors for Stroke Recurrence and Functional Outcome after Revascularization.

OBJECTIVE: Stroke in young adults is uncommon and rarely described. Moyamoya disease is one of the leading causes of stroke in young adults. We aimed to study the prognostic factors for stroke recurrences and functional outcomes in young stroke patients with moyamoya disease after revascularization. METHODS: We reviewed 696 consecutive patients with moyamoya disease admitted to our hospital from 2009-2015 and identified patients aged 18-45 years with first-ever stroke. Follow-up was conducted via face-to-face or structured telephone interviews. Outcome measures were recurrent stroke events and unfavorable functional outcomes (modified Rankin Scale >2). RESULTS: We included 121 young patients with moyamoya disease suffering from stroke (initial presentation age, 35.4 ± 7.5 years). All patients underwent revascularization after the acute phase of initial stroke events as the secondary prevention for recurrences. During follow-up (median, 40 months), 9 patients (7.4%) experienced recurrent strokes and 8 of them (6.6%) suffered unfavorable functional outcomes. In the multivariate analysis, diabetes was an independent predictor for stroke recurrences (hazard ratio 6.76; 95% confidence interval 1.30-35.11; P = 0.02) and was significantly associated with unfavorable functional outcomes (odds ratio 7.87; 95% confidence interval 1.42-38.74; P = 0.01). CONCLUSIONS: We identified diabetes as an independent risk factor for recurrent strokes and unfavorable functional outcomes after revascularization in young stroke patients with moyamoya disease.