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Objective To elucidate the clinical features, risk factors for contralateral progression, and long-term outcomes of patients with unilateral moyamoya disease (MMD). Methods We retrospectively reviewed 109 patients with unilateral MMD treated at Beijing Tiantan Hospital. Clinical features, radiologic findings, and outcomes were analyzed. Results The mean age at diagnosis was 30.8 ± 14.2 years with a one-peak distribution in the thirties. The ratio of women to men was 1.1:1. Familial occurrence was 5.5%. The primary symptoms at initial presentation were transient ischemic attack (39.4%), infarction (22%), and hemorrhage (26.6%). The distribution of the initial Suzuki stage was as follows: stage 2, n = 33; stage 3, n = 35; stage 4, n = 27; stage 5, n = 11, and stage 6, n = 3. Contralateral abnormality on initial angiography occurred in 19 adult patients (17.4%). Posterior cerebral artery involvement was observed in 28 (25.7%) patients. During the average follow-up of 43.8 ± 21.3 months, contralateral progression was observed in 18 patients (16.5%). Contralateral abnormalities ( P = 0.033) on initial angiography and infarction at initial presentation ( P = 0.041) were significantly associated with contralateral progression in adults and children, respectively. Approximately 91.7% of patients had a modified Rankin Scale score of 0–2 during follow-up. Conclusions A one-peak pattern in age distribution, lower grade of Suzuki stage, fewer familial cases, and posterior cerebral artery involvement were observed in patients with unilateral MMD. Contralateral abnormalities on initial angiography and infarction at onset were risk factors for contralateral progression in adult and pediatric patients, respectively. Good functional outcomes can be anticipated in the vast majority of surgically treated patients. [ABSTRACT FROM AUTHOR]

Dual antiplatelet therapy (DAPT) of aspirin plus clopidogrel is commonly used in patients with unruptured intracranial aneurysms treated with stent-assisted coil (SAC) embolization. However, the unpredictable clopidogrel efficacy of the 5%–55% nonresponders limits its use. Ticagrelor, as a potential alternative of clopidogrel, is an antiplatelet agent with low resistance rates but uncertain efficacy and safety in these patients. A single-center cohort study was performed to compare the efficacy and safety of ticagrelor with clopidogrel in the DAPT regimen in patients with unruptured intracranial aneurysms and treated with SAC. The patients with clopidogrel resistance identified as inadequate adenosine diphosphate inhibition rate determined by thromboelastography were treated with ticagrelor instead, and both drugs achieved adequate suppression of platelet aggregation when stents were implanted. The occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) and bleeding events was recorded through 6 months follow-up. Data from 86 patients with 99 unruptured intracranial aneurysms and treated by SAC with clopidogrel were compared with those from 108 patients with 111 aneurysms and treated with ticagrelor. Neither the baseline characteristics nor the incidence of the MACCE or bleeding events differed between the groups. Ticagrelor exerted significantly higher adenosine diphosphate inhibition rate than that of the clopidogrel. Multivariable logistic regression analysis showed that the incidence of MACCE was related to hematocrit and fibrinogen levels. Ticagrelor seemed to be as effective and safe as clopidogrel for SAC in unruptured intracranial aneurysms. Hematocrit and fibrinogen levels were independent risk factors for the incidence of MACCE. [ABSTRACT FROM AUTHOR]

Moyamoya disease (MMD) is a cerebrovascular disorder, currently defined as progressive stenosis of intracranial internal carotid artery and its main branches with secondary formation of netlike vessels. Its precise formation mechanism, however, is unknown. We propose that MMD is caused by abnormal embryonic development of the cerebral arteries and also propose a mechanism for MMD formation. The anterior, middle, and posterior cerebral arteries, anterior choroidal arteries (AChoA) and posterior choroidal arteries, and posterior corpus callosum arteries were analyzed separately for each patient with MMD to determine whether the arteries exhibited the following characteristics, which we regarded as remnants of primitive vessels: 1) plexiform arteries rather than normal artery trunks; 2) clustered arteries converging at locations of normal artery trunks; and 3) dilated AChoA. We retrospectively analyzed 39 consecutive patients with MMD, of whom 30 had anterior cerebral arteries, 31 middle cerebral arteries, 10 posterior cerebral arteries, 30 AChoAs, 18 posterior choroidal arteries, and 20 posterior corpus callosum arteries and had the characteristics of primitive vessel remnants. Altogether, 82.05% of the patients had the remnants of primitive vessels. MMD is more likely to be caused by abnormalities of cerebral artery development, which mainly occur in the embryonic period or postnatally. The abnormality developing processes include sprouting angiogenesis, vessel fusion, and pruning, which primarily affect cranial ramus of primitive internal carotid artery, may occasionally affect the caudal ramus of the primitive internal carotid artery, and rarely affect the vertebrobasilar artery system. So-called moyamoya vessels comprise unfused primitive small vessels; to compensate, enlarged AChoAs remain undegenerated but are not dilated. [ABSTRACT FROM AUTHOR]

Recurrent stroke after surgical revascularization is still a big issue for moyamoya disease (MMD). This study aims to identify predictors for postoperative stroke and unfavorable outcome in ischemic-type MMD. We identified a consecutive series of patients with ischemic-type MMD who underwent revascularization between January 2005 and December 2012. Predictors for postoperative stroke and functional outcomes were assessed with logistic and Cox regression analysis. A total of 346 patients underwent 437 revascularization procedures and the mean follow-up period was 4.0 years. The incidence of perioperative stroke was 6.9%. Being adult at onset (odds ratio [OR], 5.033; 95% confidence interval [CI], 1.447–17.506; P = 0.011) and posterior cerebral artery (PCA) stenosis (OR, 3.364; 95% CI, 1.588–7.265; P = 0.002) before surgery were predictors of perioperative stroke. The annual subsequent stroke rate beyond 30 days after surgery was 1.2%. Subsequent stroke events tended to occur throughout the first 5 years after surgery in adults, whereas in children they mainly occurred within the first 2 years after surgery. Age at onset (OR, 1.025; 95% CI, 1.003–1.048; P = 0.023), ischemic stroke or transient ischemic attack at presentation (OR, 2.703; 95% CI, 1.062–6.875; P = 0.037), and PCA involvement (OR, 2.664; 95% CI, 1.462–4.854; P = 0.001) were associated with higher risk of overall postoperative stroke. PCA involvement (OR, 2.62; 95% CI, 1.33–5.15; P = 0.005), internal carotid artery supraclinoid segment occlusion (OR, 2.76; 95% CI, 1.27–6.03; P = 0.011), and older age at onset (OR, 1.03; 95% CI, 1.01–1.05; P = 0.033) were predictive of unfavorable outcome. Patients with ischemic-type MMD at an older age and more severe angiopathy might be at higher risk of recurrent stroke and unfavorable outcome after revascularization. [ABSTRACT FROM AUTHOR]

Objective To elucidate the clinical features of patients with hemorrhagic moyamoya disease (MMD) in China. Methods We retrospectively reviewed 471 patients with hemorrhagic MMD at Beijing Tiantan Hospital. Clinical features and radiologic findings were analyzed. Results The mean age at diagnosis was 35.3 ± 11.5 years, with 1 peak distribution in patients from 35 to 39 years of age. The ratio of women to men was 1.2:1. Familial occurrence was 3.8%. The primary symptoms at initial presentation were intraventricular hemorrhage (42.0%), intracerebral hemorrhage (23.6%), intracerebral hemorrhage with intraventricular hemorrhage (18.3%), and subarachnoid hemorrhage (16.1%). Before the diagnosis, 68 patients experienced a second episode of bleeding. Rebleeding tends to be common within 6 years after the first bleeding (83.8%). The second bleeding episode was characterized by a change in which hemisphere bleeding occurred in 7 patients (10.3%) and by the type of bleeding in 23 patients (33.8%). Most patients presented with Suzuki stage 3 or 4 MMD (61.7%). Posterior cerebral artery involvement was observed in 28 (18.4%) patients. Forty-three intracranial aneurysms were identified in 39 patients (8.3%). Conclusions A 1-peak pattern in age distribution and mild female dominance in sex distribution were observed in patients with hemorrhagic MMD. Rebleeding tends to be common within 6 years after the first bleeding; however, some cases of rebleeding occur after a long period. Furthermore, the second bleeding episode was characterized frequently by a change in hemisphere and the type of bleeding. Early surgical treatment in both hemispheres is recommended. [ABSTRACT FROM AUTHOR]

Background Different gene expression profiles are observed in intracranial aneurysm tissues. Understanding these genes and what regulates their expression will provide insight into the pathogenesis of intracranial aneurysms. We investigated whether differences in DNA methylation regulate gene expression in intracranial aneurysms. Methods We compared 20 intracranial aneurysm tissue specimens with 20 matched specimens from the superficial temporal artery as controls. We identified the gene expression profiles in these samples using the GeneChip Human U133 Plus 2.0 array and evaluated DNA methylation modifications using the Infinium HumanMethylation450 BeadChip Kit. Results A total of 11,022 differentially methylated sites between aneurysm tissues and matched control tissues were identified, and 2142 differentially expressed gene transcripts were detected based on the 2 gene expression profiles. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses and verification analysis showed that the MYH11 , LIFR , and TLR4 genes were associated with the occurrence and development of intracranial aneurysms. These genes mainly encode cell adhesion molecules or are involved in the NF-κB, JAK-STAT, and ERK/JNK signaling pathways. Conclusions In the development of intracranial aneurysms, DNA methylation plays an important role in the regulation of genetic expression involved in immune and inflammatory reactions, cell function, cell maintenance, and cell signal transduction. [ABSTRACT FROM AUTHOR]

Objective To investigate the long-term outcomes after conservative and direct surgical treatment for patients with moyamoya disease (MMD) at late Suzuki stage. Methods We retrospectively reviewed 82 patients (164 hemispheres) with MMD at late Suzuki stage at Beijing Tiantan Hospital. Clinical features, radiologic findings, and outcomes were analyzed. Results The mean age at diagnosis was 36.4 ± 11.7 years. The distribution of the initial Suzuki stage of MMD was as follows: stage 4, n = 113; stage 5, n = 45; stage 6, n = 6, posterior cerebral artery involvement was observed in 41 hemispheres (25.0%). The incidence of postoperative stroke (<48 hours) was 6.7%. During the average follow-up of 55.1 ± 16.2 months, including postoperative and follow-up strokes, 7 of 75 conservatively treated hemispheres (9.3%) and 9 of 89 surgically treated patients (10.1%) experienced a stroke event; there was no statistical significance in the Kaplan-Meier curve of stroke incidence between the surgical group and conservative group (log-rank test, P = 0.848). However, the rate of perfusion improvement in direct bypass surgically treated patients was higher than in those conservatively treated patients 3 months after discharge ( P < 0.05). Conclusions Although direct bypass surgery was shown to effectively improve the cerebral perfusion in patients with MMD at late Suzuki stage, compared with conservative treatment, it did not reduce the risk of recurrent stroke. Further study is needed to determine whether direct bypass surgery is effective in patients with MMD at late Suzuki stage. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective To compare two 3-dimensional (3D) printed models of intracranial aneurysms for simulation and training for complex aneurysm surgery. Methods The study included 6 complex or large aneurysm cases. We printed two 3D models of complex aneurysms based on computed tomography angiography data using a 3D printer: a whole model, which was all-in-one printed hollow aneurysm method with colorful and multiple materials and included the hollow aneurysm, adjacent arteries, skull base, and nerves, and a regional model that included the hollow aneurysm and adjacent arteries. The 3D models were used for surgical planning and for practice in craniotomy and clipping. Neurosurgeons rated the models via questionnaires. Results Both 3D aneurysm models were accurate: the diameter, width, and neck of the aneurysms in the models were not significantly different from the computed tomography angiography data ( P > 0.05). Furthermore, the models were useful for selecting clips before surgery. The whole 3D model improved understanding of the surgical view more than the regional model did ( P < 0.05); however, the clip application felt more realistic in the regional model ( P < 0.05). The process time for making the whole model is shorter ( P < 0.05) but more expensive ( P < 0.05) compared with the regional model. Conclusions The whole and regional 3D printed aneurysm models were accurate. The whole model was more useful for planning the trajectory of approach to the aneurysm when it was located in close proximity to bone and nerves, whereas the regional 3D aneurysm model was appropriate for aneurysms not involving bone and nerves. This will help neurosurgeon choose the proper 3D model for the complex aneurysm surgery according to the comparison. [ABSTRACT FROM AUTHOR]

Objective To study clinical outcome of giant intracranial aneurysms (diameter ≥25 mm) treated with different surgical modalities and to analyze factors affecting prognosis. Methods A retrospective analysis was performed of 204 consecutive patients with giant intracranial aneurysms who underwent surgical treatment in our department from 1995 to 2008. Clinical outcome was evaluated with the Glasgow Outcome Scale. Results Surgical modalities included direct aneurysm neck clipping in 102 patients (50.0%), parent artery reconstruction in 51 patients (25.0%), proximal artery ligation in 23 patients (11.3%; 4 patients combined with revascularization), trapping in 26 patients (12.7%), and wrapping in 2 patients (1.0%). Follow-up data were available for 181 patients (88.7%), with a mean follow-up period of 62 months (range, 12–164 months). A good outcome (Glasgow Outcome Scale score 5) was observed in 114 patients (63.0%), and a poor outcome (Glasgow Outcome Scale score 1–4) was observed in 67 patients (37.0%). Independent factors that affected prognosis were age and location of aneurysm. Older age (≥50 years) and location of aneurysm in posterior circulation were associated with poor outcome. In 85 patients with preoperative subarachnoid hemorrhage, patients with a higher Hunt and Hess grade (≥3) had a worse outcome compared with patients with a low Hunt and Hess grade (1 or 2). Surgical modalities and other factors were not significantly associated with clinical outcome. Conclusions Giant intracranial aneurysms are effectively treated with craniotomy and surgical treatment. Older age, aneurysm location in posterior circulation, and higher Hunt and Hess grade are risk factors affecting prognosis. [ABSTRACT FROM AUTHOR]

Objective To elucidate the clinical features, surgical treatment, and long-term outcome in elderly patients with moyamoya disease (MMD). Methods We retrospectively reviewed 87 elderly patients with MMD at Beijing Tiantan Hospital. Clinical features, radiologic findings, and outcomes were analyzed. Results The mean age at diagnosis was 54.0 ± 3.7 years. Familial occurrence was 2.3%. Underlying vascular risk factors was 74.7%. Infarction was the most common symptom in elderly MMD (40.2%). Most patients presented with Suzuki stage 4 or 5 MMD (51.2%). Posterior cerebral artery involvement was observed in 22 (25.3%) patients. The incidence of postoperative infarction or hemorrhages was 6.9%. Diabetes was identified as a predictor of adverse postoperative events. During the average follow-up of 35.5 ± 22.2 months, rebleeding in patients with hemorrhagic MMD was higher than in those with ischemic MMD ( P < 0.05). What's more, the rate of perfusion improvement in surgically treated patients was higher than in conservatively treated patients 3 months after discharge ( P < 0.05). Conclusions Infarction was the most common symptom in elderly MMD. More vascular risk factors, a higher grade of Suzuki stage, fewer familial cases, and posterior cerebral artery involvement were observed in elderly patients with MMD. Diabetes was a risk factor of postoperative events for elderly patients. Hemorrhagic MMD had a higher rate of rebleeding than the ischemic type. Although surgical revascularization procedures can improve cerebral perfusion, further study is needed to determine whether surgical revascularization is effective in elderly patients or with certain techniques. [ABSTRACT FROM AUTHOR]

Background and Purpose Moyamoya disease (MMD) is a chronic cerebrovascular disorder with little known etiology. We aim to propose a new classification system for MMD from the perspective of embryology. Methods MMD patients' digital subtraction angiograms were retrospectively analyzed. Every angiogram was analyzed to find the abnormal vessels and from which part of the posterior cerebral artery (PCA) the lesions begin. Results In 262 MMD cases, 32 pediatric patients had PCA involvement, of which 17 were male and 15 were female; 68 adults had PCA involvement, of which 33 were male and 35 were female. The initially affected part of the PCA was compared between sexes and between pediatric and adult patients, and the findings are not statistically significant ( P = 0.233, P = 0.855, P = 0.343, respectively). However, of the 100 cases with PCA involvement, only 4 had the lesions begin from the first part of the PCA, and all of the 4 cases had the basilar artery lesions. All the other 96 cases had the lesions begin from the second part of the PCA or from the posterior communication artery, which is derived from the caudal ramus of the primitive intracarotid artery, leaving the first part of the PCA and basilar artery excluded from affection. Conclusion MMD should be classified into primitive intracarotid artery system–involved type and primitive vertebral basilar artery system–involved type. The reason that the vertebral basilar artery is so rarely involved in MMD might be because of its late development in the brain. [ABSTRACT FROM AUTHOR]

Background The diagnosis of moyamoya disease (MMD) is often uncertain. Moyamoya syndrome (MMS) is often misdiagnosed as MMD. High-resolution magnetic resonance imaging (HR-MRI) enables vessel wall assessment to obtain more precise diagnoses. The aim of this study was to determine the true etiologies of arterial steno-occlusion in patients with an angiographic diagnosis of MMD or MMS using HR-MRI. Methods HR-MRI was performed in 21 adult patients with angiographically proven MMD or MMS. A definite diagnosis was based on the HR-MRI findings. The diagnoses made via the 2 different imaging technologies were compared, and significant findings were analyzed. Results A total of 21 patients were enrolled, including 7 patients with angiographically proven MMD and 14 patients with angiographically proven MMS. Among the 7 patients with MMD, HR-MRI confirmed the diagnosis of MMD in 6; the remaining patient was considered to have atherosclerosis in the bilateral distal internal carotid arteries (ICAs) and the left middle cerebral artery. Among the 14 patients with MMS, HR-MRI confirmed MMD in 6 patients (including 2 patients with unilateral MMD), atherosclerosis in 5 patients (including 3 patients with bilateral atherosclerosis and 2 with unilateral atherosclerosis), arterial dissection of the left ICA in 1 patient, and MMD in the left cerebral hemisphere with atherosclerosis in the right hemisphere in 2 patients. Conclusions Differentiating MMD from MMS is difficult in certain situations, and HR-MRI may help provide a more in-depth understanding of MMD and MMS, thereby achieving a more reliable diagnosis. [ABSTRACT FROM AUTHOR]

Objective To investigate long noncoding ribonucleic acid (lncRNA) expression patterns in adult moyamoya disease (MMD) patients and explore their possible roles in the pathophysiology of MMD. Methods A healthy control group ( n = 10) and an MMD group ( n = 15) were evaluated. RNA was extracted from peripheral blood samples and hybridized to microarray to get lncRNA expression profiles. Then predicted lncRNA target genes were identified, and bioinformatics analysis was performed to investigate their molecular functions. Results In the MMD group, 3649 lncRNAs exhibited more than 2-fold expression than their counterparts in the healthy control group; of these, 1494 were upregulated, while 2155 were downregulated. Principal component analysis and Hclust analysis produced completely different clusters between the 2 groups. Gene ontology and KEGG pathway enrichment analysis suggested that the differentially expressed lncRNAs regulate multiple signaling pathways that were related with inflammation and vascular disease, and mitogen-activated protein kinase (MAPK) signaling pathway was the core regulatory pathway. Conclusions Long noncoding RNA expression profiles were quite different between MMD and control groups. Multiple signaling pathways that were closely associated with immune response, vasculogenesis, and smooth muscle contraction were indicated to participate in lncRNAs regulatory mechanism; of these, MAPK signaling pathway, which has been well studied for the treatment of many other cardiovascular diseases, was the core of this regulatory network. Our findings could help further understand the pathophysiology of MMD and provide new potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Objective To elucidate the clinical and angiographic features in patients with moyamoya disease (MMD) and the p.R4810K heterozygous variant and present an angiographic grading system to evaluate disease severity. Methods We retrospectively reviewed 87 patients with MMD and the p.R4810K variant treated at Beijing Tiantan Hospital. Clinical features, stroke subtype, and angiographic characteristics were analyzed. Results The median age at diagnosis was 25 years (range, 3–59). The ratio of women to men was 1.2:1. The familial occurrence of MMD was 14.9%. The primary symptom at diagnosis was ischemia, hemorrhage, or other in 67, 16, and 4 patients, respectively. Angiographic features correlating with ischemic stroke or stroke, including Suzuki grade, external carotid artery collaterals, leptomeningeal collaterals, and Mugikura grade, were identified. A binary logistic regression model demonstrated a significant correlation of Suzuki grade ( P = 0.008) and posterior cerebral artery grade ( P = 0.029) with ischemic stroke (142 hemispheres). A modified Suzuki-Mugikura grading system was developed. The areas under the receiver operating characteristic curves used to predict ischemic stroke based on the Suzuki grading, Mugikura grading, and modified Suzuki-Mugikura grading systems were 0.736, 0.69, and 0.741, respectively. Furthermore, the modified Suzuki-Mugikura grades were significantly correlated with infarction in posterior circulation and the number of infarcted regions. Conclusions The clinical and angiographic features of a Chinese MMD population with the p.R4810K variant were similar to those of a Japanese MMD population; they might be a distinct cerebrovascular disease entity and represent a separate subgroup. A modified Suzuki-Mugikura grading system was valuable for predicting stroke and evaluating disease severity. [ABSTRACT FROM AUTHOR]

Background Quasi-moyamoya disease (MMD) is characterized by moyamoya vasculopathy and well-recognized comorbidity. Whether the recently identified MMD susceptibility gene variant, p.R4810K (rs112735431), is associated with quasi-MMD remains unclear. Methods This study was a 2-hospital–based case–control study that was conducted in the neurosurgical departments of Beijing Tiantan Hospital and Peking University International Hospital. A total of 42 patients and 161 controls were enrolled. The p.R4810K polymorphism was assessed with Sanger sequencing. A review of the pertinent literature on the p.R4810K polymorphism and quasi-MMD was performed. Results The mean age of patients at diagnosis was 34.9 ± 16.5 years with a one-peak distribution in the forties; 57.1% of the patients were female. The p.R4810K heterozygous variant was identified in 5 patients, including 3 patients with atherosclerosis, 1 patient with Graves disease, and 1 patient with rheumatoid arthritis; it was also observed in one control. The frequencies of the A allele and the G/A genotype of rs112735431 (p.R4810K) were significantly greater in the patients with quasi-MMD than in the control groups (5.95% vs. 0.31%, odds ratio [OR] 20.316, P = 0.002; 11.9% vs. 0.6%, OR 21.622, P = 0.002, respectively). In the subgroup analysis, the rs112735431 G/A genotype was significantly associated with arteriosclerotic or autoimmune quasi-MMD ( P = 0.006, OR 25.263, confidence interval 2.501–255.175; P = 0.015, OR 29.091, confidence interval 2.444–346.334, respectively). Conclusions The p.R4810K variant was associated with atherosclerotic and autoimmune quasi-MMD in a Chinese population, and a lower prevalence of this variant in patients with quasi-MMD compared with patients with MMD was observed. [ABSTRACT FROM AUTHOR]