Wilms' tumour 1-associating protein inhibits endothelial cell angiogenesis by m6A-dependent epigenetic silencing of desmoplakin in brain arteriovenous malformation.

Brain arteriovenous malformations (AVMs) are congenital vascular abnormality in which arteries and veins connect directly without an intervening capillary bed. So far, the pathogenesis of brain AVMs remains unclear. Here, we found that Wilms' tumour 1-associating protein (WTAP), which has been identified as a key subunit of the m6A methyltransferase complex, was down-regulated in brain AVM lesions. Furthermore, the lack of WTAP could inhibit endothelial cell angiogenesis in vitro. In order to screen for downstream targets of WTAP, we performed RNA transcriptome sequencing (RNA-seq) and Methylated RNA Immunoprecipitation Sequencing technology (MeRIP-seq) using WTAP-deficient and control endothelial cells. Finally, we determined that WTAP regulated Desmoplakin (DSP) expression through m6A modification, thereby affecting angiogenesis of endothelial cells. In addition, an increase in Wilms' tumour 1 (WT1) activity caused by WTAP deficiency resulted in substantial degradation of ß-catenin, which might also inhibit angiogenesis of endothelial cells. Collectively, our findings revealed the critical function of WTAP in angiogenesis and laid a solid foundation for the elucidation of the pathogenesis of brain AVMs.

Aspirin and Growth of Small Unruptured Intracranial Aneurysm: Results of a Prospective Cohort Study.

BACKGROUND AND PURPOSE: The role of aspirin in unruptured intracranial aneurysm (UIA) growth remains largely unknown. We aim to identify whether aspirin is associated with a lower rate of UIA growth in patients with UIA <7 mm. METHODS: This prospective cohort study consecutively enrolled patients with UIAs <7 mm with ischemic cerebrovascular disease between January 2016 and December 2019. Baseline and follow-up patient information, including the use of aspirin and blood pressure level, were recorded. Patients were considered aspirin users if they took aspirin, including standard- and low-dose aspirin, ≥3× per week. The primary end point was aneurysm growth in any direction or an indisputable change in aneurysm shape. RESULTS: Among the 315 enrolled patients, 272 patients (86.3%) underwent imaging examinations during follow-up (mean follow-up time, 19.6±12.7 months). A total of 113 patients were continuously treated with aspirin. UIA growth occurred in 31 (11.4%) patients. In the multivariate Cox analysis, specific aneurysm locations (anterior communicating artery, posterior communicating artery, or middle cerebral artery; hazard ratio, 2.89 [95% CI, 1.22-6.88]; P=0.016) and a UIA size of 5 to <7 mm (hazard ratio, 7.61 [95% CI, 3.02-19.22]; P<0.001) were associated with a high risk of UIA growth, whereas aspirin and well-controlled blood pressure were associated with a low risk of UIA growth (hazard ratio, 0.29 [95% CI, 0.11-0.77]; P=0.013 and hazard ratio, 0.25 [95% CI, 0.10-0.66]; P=0.005, respectively). The cumulative annual growth rates were as high as 40.0 and 53.3 per 100 person-years in the high-risk patients (>1 risk factor) with and without aspirin, respectively. CONCLUSIONS: Aspirin therapy and well-controlled blood pressure are associated with a low risk of UIA growth; the incidence of UIA growth in high-risk patients in the first year is high, warranting intensive surveillance in this patient group. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02846259.

N6-methyladenosine methyltransferase METTL3 affects the phenotype of cerebral arteriovenous malformation via modulating Notch signaling pathway.

BACKGROUND: Cerebral arteriovenous malformation (AVM) is a serious life-threatening congenital cerebrovascular disease. Specific anatomical features, such as nidus size, location, and venous drainage, have been validated to affect treatment outcomes. Until recently, molecular biomarkers and corresponding molecular mechanism related to anatomical features and treatment outcomes remain unknown. METHODS: RNA N6-methyladenosine (m6A) Methyltransferase METTL3 was identified as a differentially expressed gene in groups with different lesion sizes by analyzing the transcriptome sequencing (RNA-seq) data. Tube formation and wound healing assays were performed to investigate the effect of METTL3 on angiogenesis. In addition, Methylated RNA Immunoprecipitation Sequencing technology (MeRIP-seq) was performed to screen downstream targets of METTL3 in endothelial cells and to fully clarify the specific underlying molecular mechanisms affecting the phenotype of cerebral AVM. RESULTS: In the current study, we found that the expression level of METTL3 was reduced in the larger pathological tissues of cerebral AVMs. Moreover, knockdown of METTL3 significantly affected angiogenesis of the human endothelial cells. Mechanistically, down-regulation of METTL3 reduced the level of heterodimeric Notch E3 ubiquitin ligase formed by DTX1 and DTX3L, thereby continuously activating the Notch signaling pathway. Ultimately, the up-regulated downstream genes of Notch signaling pathway dramatically affected the angiogenesis of endothelial cells. In addition, we demonstrated that blocking Notch pathway with DAPT could restore the phenotype of METTL3 deficient endothelial cells. CONCLUSIONS: Our findings revealed the mechanism by which m6A modification regulated the angiogenesis and might provide potential biomarkers to predict the outcome of treatment, as well as provide suitable pharmacological targets for preventing the formation and progression of cerebral AVM.

Natural Course of Moyamoya Disease in Patients With Prior Hemorrhagic Stroke.

Background and Purpose- Evidence on the natural history of hemorrhagic moyamoya disease is still insufficient. We investigated the incidence of recurrent intracranial bleeding, mortality, and risk factors for rebleeding in patients with moyamoya disease. Methods- A total of 128 conservatively managed patients with hemorrhagic presentation and complete follow-up data were included. Recurrent hemorrhages during long-term follow-up were documented. Annual and cumulative incidence rate of bleeding was generated via Kaplan-Meier survival analysis, and risk factors were analyzed using logistic regression analysis. Results- The median follow-up time was 10.1 (1-27) years. During a total of 1300.7 patient-years, 47 (36.7%) patients experienced 59 occurrences of recurrent hemorrhages, rendering an average annual incidence of 4.5%. Among them, 9 patients (19.1%) died from rebleeding and 12 patients sustained severe disability (modified Rankin Scale score of ≥3). The cumulative risk of rebleeding was 7.8% at 5 years, 22.6% at 10 years, and 35.9% at 15 years. Only 4 (3.1%) patients experienced ischemic stroke, yielding an average annual incidence of 0.3%. Multivariate analysis showed that smoking (odds ratio, 4.85; P=0.04) was an independent risk factor of rebleeding. Rebleeding (hazard ratio, 11.04; P=0.02) and hypertension (hazard ratio, 4.16; P=0.04) were associated with increased mortality. Age, type of initial bleeding, digital subtraction angiography staging, family history, and coexisting cerebral aneurysms were not associated with increased risk of rebleeding. Conclusions- Rebleeding events were common and the main cause of death in patients with hemorrhagic moyamoya disease. The risk of rebleeding steadily increased during long-term follow-up. Smoking was a risk factor for rebleeding, and hypertension was associated with increased mortality.

Decreased level of irisin, a skeletal muscle cell-derived myokine, is associated with post-stroke depression in the ischemic stroke population.

BACKGROUND: Depression is a frequent mood disorder in stroke patient. Our aim was to determine irisin levels in serum and investigate their associations with post-stroke depression (PSD) in a 6-month follow-up study in Chinese patients with first-ever acute ischemic stroke (AIS). METHODS: The subjects were first-ever AIS patients who were hospitalized at three stroke centers during the period from January 2015 to December 2016. Neurological and neuropsychological evaluations were conducted at the 6-month follow-up. Serum irisin concentrations were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: During the study period, 1205 patients were included in the analysis. There were 370 patients (30.7%) classified as depression. The depression distribution across the irisin quartiles ranged between 49.8% (first quartile) and 9.9% (fourth quartile). In the patients with depression, serum irisin levels were lower compared with those in patients without depression (P < 0.001). In a multivariate model using the first (Q1) quartile of irisin vs. Q2-4 together with the clinical variables, the marker displayed predictive information and increased risk of PSD by 75% (odds ratio [OR] for Q1, 1.75 [95% confidence interval [CI], 1.15-2.65]). In addition, a model containing known risk factors plus irisin compared with a model containing known risk factors without irisin showed a greater discriminatory ability; the area under the curve (AUC) increased from 0.77 to 0.81 (95% CI, 0.76-0.86). CONCLUSIONS: The data suggested that reduced serum levels of irisin were powerful biological markers of risk of developing PSD even after adjustment by variables. Further studies are necessary to confirm this association, which may open the way to the proposal of new therapeutic options. TRIAL REGISTRATION: ChiCTR-OPC-17013501 . Retrospectively registered 23 September 2017.

Surgical management of giant intrapetrous internal carotid aneurysm presenting with coil exposure after endovascular treatment.

Giant intrapetrous internal carotid aneurysms (petrous ICA aneurysm) are rare. A giant petrous ICA aneurysm presenting with otorrhagia and coil exposure to the external auditory meatus (EAM) after endovascular treatment has never been documented before. The authors report here a case of successful surgical trapping with bypass intervention of a giant petrous ICA aneurysm presenting with coil exposure after endovascular treatment. A 58-year-old man presented with persistent otorrhagia having been admitted to our hospital because of the recurrence of a giant petrous ICA aneurysm after repeated embolization treatments with coils. An electronic otoscope examination demonstrated that a piece of coil escaped into his right EAM. After multidisciplinary consultation, an extracranial-intracranial (EC-IC) bypass with ICA occlusion and coil removal with a closed EAM filling were performed in stages. The patient recovered quickly without any neurological deficits. A digital subtraction angiography confirmed the absence of the aneurysm and patency of the bypass graft.

MAGI3 Suppresses Glioma Cell Proliferation via Upregulation of PTEN Expression.

OBJECTIVE: To investigate the role and molecular mechanism of membrane-associated guanylate kinase inverted 3 (MAGI3) in glioma cell proliferation. METHODS: The expression levels of MAGI3 and PTEN were assessed in glioma samples by Western blotting. MAGI3 was stably transfected into C6 glioma cells to obtain C6-MAGI3 cells. Then, the proliferation, the expression levels of MAGI3 and PTEN, and Akt phosphorylation were evaluated in C6 and C6-MAGI3 cells. Xenograft tumor models were established by subcutaneous injection of C6 and C6-MAGI3 cells into nude mice, and the growth rates of xenografts in the mice were compared. The potential role of MAGI3 expression in PI3K/Akt signaling activation was further investigated by examining the correlation between MAGI3 expression and the expression of PI3K/Akt signaling downstream target genes in a glioma dataset using gene set enrichment analysis (GSEA). RESULTS: Expression levels of MAGI3 and PTEN were significantly downregulated in gliomas. Overexpression of MAGI3 in the glioma C6 cell line upregulated PTEN protein expression, inhibited the phosphorylation of Akt, and suppressed cell proliferation. MAGI3 overexpression also inhibited the growth of C6 glioma tumor xenografts in nude mice. Analysis based on the GEO database confirmed the negative correlation between activation of PI3K/Akt pathway and MAGI3 mRNA levels in human glioma samples. CONCLUSION: The loss of MAGI3 expression in glioma may enhance the proliferation of glioma cells via downregulation of PTEN expression, leading to the activation of the PI3K/Akt pathway. MAGI3 is a potential glioma suppressor.

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.

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.

The incidence of cerebral amyloid angiopathy in surgically treated intracranial hemorrhage in the Chinese population.

Despite being widely accepted as an important cause of spontaneous intracranial hemorrhage (ICH), cerebral amyloid angiopathy (CAA) has seldom been studied in the Chinese population. The current study aims to investigate the incidence and features of CAA in surgically treated ICH patients in China. From May 2006 to April 2011, 974 patients admitted to 71 hospitals throughout China for acute spontaneous ICH were studied. Craniotomy for hematoma evacuation was performed. Brain tissue from the superficial side of the suspected residual hematoma cavity, as well as from the cortex and subcortex, was obtained. Congo Red stain and ß-amyloid immunohistochemistry were used for the diagnosis. Each case was assigned a pathological severity score. Of the 974 involved patients, 37.7% were identified with CAA of different degrees. CAA had positive correlation with age and was independent of sex. Most patients had mild CAA with only the superficial vessels involved in lobes instead of the basal ganglia; the patients ≥65 years had more severe pathological score of CAA than those <65 years and had more lobes and cerebellum involved than the latter. More than one third of the surgically treated Chinese ICH patients may have CAA of different degrees.

[Melanocytic neoplasms of central nervous system analysis].

OBJECTIVE: To explore the clinical manifestations, diagnosis, treatment and prognostic features of melanocytic neoplasms of central nervous system (CNS). METHODS: A total of 24 patients with melanocytic neoplasms of CNS underwent surgery and were confirmed pathologically our hospital during 2006 - 2012. Their clinical data were collected. There were primitive melanocytic neoplasms (n = 8) and metastatic melanoma (n = 16) according to the diagnostic criteria of Willis. The scans of magnetic resonance imaging (MRI) showed hyper-intensity on T1 weighted image (n = 15) and hypo-intensity on T2 weighted image (n = 20). RESULTS: The outcomes were total resection (n = 11), subtotal resection (n = 9) and partial resection (n = 4). All 8 primitive melanocytic neoplasms were followed up. Among them, 2 cases died postoperatively at 15 and 40 months respectively. The remaining 6 cases survived 13 - 56 months after craniotomy. And 14/16 patients of metastatic melanoma were followed up, 8 cases died and the mean survival period was 4.5 months. The remaining 6 cases survived 1-7 months after craniotomy. Immunohistochemical staining demonstrated that the positive rate of HMB-45 was 9/10, S-100 9/11 and Vimentin 8/11. CONCLUSION: Melanocytic neoplasms of CNS are rare lesions with characteristic MRI features. Immunohistochemical staining helps to reach a definite pathological diagnosis. Surgical excision is recommended. Differentiation of primary and metastatic neoplasm is critical for prognostic evaluations.

[Surgical treatment of ruptured cerebellar arteriovenous malformations].

OBJECTIVE: To analyze the clinical characteristics and surgical outcomes of ruptured cerebellar arteriovenous malformations (AVM). METHODS: The clinical data were retrospectively analyzed for 676 brain AVM patients. Among them, 616 cases were treated at Beijing Tiantan Hospital from January 2003 to December 2009 and 32 cases of them were of cerebellar AVM. Another 60 cases of intracranial AVM were managed at Beijing Chaoyang Hospital from January 2003 to December 2011 and there were 8 cases of cerebellar AVM. Microsurgery was performed to remove hematoma and excise AVM. And the postoperative outcomes were evaluated. RESULTS: Statistics analysis of activities of daily living (ADL) scores for 636 cases of cerebral AVM and 40 cases of cerebellar AVM showed no significant difference. Among 40 cases of cerebellar AVM, hemorrhage occurred first in 35 (87.5%) patients. Postoperative re-examinations of computed tomography revealed the resolution of hematoma and the absence of re-hemorrhage. Digital subtraction angiography (DSA) examinations were performed in 39 cases and no residual nidus was observed. Tonsillar herniation occurred preoperatively in 1 case and DSA was not re-examined. There were balance dysfunction (n = 3), dysarthria (n = 2) and dystaxia and dysphasia (n = 1). The postoperative ADL degrees were I(n = 26), II(n = 10), III(n = 3) and IV(n = 1). During a follow-up period of 6 months, no re-hemorrhage occurred and there was no worsening function of central nerve system. CONCLUSION: Emergency microsurgery is effective in the treatment of ruptured cerebellar AVM.

[Preoperative location of major language functional cerebral areas using functional magnetic resonance imaging].

OBJECTIVE: To design a set of functional magnetic resonance imaging (fMRI) tasks to activate the major Chinese language functional areas. METHODS: Eight volunteers and 3 patients received fMRI studies with the tasks of semantic judgment, word reading and listening comprehension. Brain activation map of each task was obtained after standard fMRI data processing. RESULTS: The fMRI examination with 3 tasks activated middle frontal gyrus (BA 9), Broca area and Wernicke area respectively. CONCLUSION: A set of fMRI examinations, including semantic judgment, word reading and listening comprehension, can activate the major Chinese language functional areas steadily and may be used as a preoperative localizer of language areas.

Somatic GJA4 mutation in intracranial extra-axial cavernous hemangiomas.

OBJECTIVE: Extra-axial cavernous hemangiomas (ECHs) are sporadic and rare intracranial occupational lesions that usually occur within the cavernous sinus. The aetiology of ECHs remains unknown. METHODS: Whole-exome sequencing was performed on ECH lesions from 12 patients (discovery cohort) and droplet digital polymerase-chain-reaction (ddPCR) was used to confirm the identified mutation in 46 additional cases (validation cohort). Laser capture microdissection (LCM) was carried out to capture and characterise subgroups of tissue cells. Mechanistic and functional investigations were carried out in human umbilical vein endothelial cells and a newly established mouse model. RESULTS: We detected somatic GJA4 mutation (c.121G>T, p.G41C) in 5/12 patients with ECH in the discovery cohort and confirmed the finding in the validation cohort (16/46). LCM followed by ddPCR revealed that the mutation was enriched in lesional endothelium. In vitro experiments in endothelial cells demonstrated that the GJA4 mutation activated SGK-1 signalling that in turn upregulated key genes involved in cell hyperproliferation and the loss of arterial specification. Compared with wild-type littermates, mice overexpressing the GJA4 mutation developed ECH-like pathological morphological characteristics (dilated venous lumen and elevated vascular density) in the retinal superficial vascular plexus at the postnatal 3 weeks, which were reversed by an SGK1 inhibitor, EMD638683. CONCLUSIONS: We identified a somatic GJA4 mutation that presents in over one-third of ECH lesions and proposed that ECHs are vascular malformations due to GJA4-induced activation of the SGK1 signalling pathway in brain endothelial cells.

Regional cerebral perfusion and ischemic status after standard superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery in ischemic cerebrovascular disease.

BACKGROUND AND PURPOSE: Standard superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery is an effective treatment for ischemic cerebrovascular diseases, including moyamoya disease and occlusive cerebrovascular disease. Our purpose in this study was to evaluate the ischemic status based on the imaging modality of computed tomographic perfusion (CTP) before and after STA-MCA bypass in patients with moyamoya disease and occlusive cerebrovascular disease. METHODS: CTP was performed on 19 patients, comprising 10 patients with moyamoya disease and nine patients with occlusive cerebrovascular disease, preoperatively and on the third postoperative day. According to the regional cerebral microcirculatory change and modality of CTP, the regional cerebral ischemic status was graded into two stages with four substages (I1, I2, II1, and II2) to indicate the regional cerebral perfusion and ischemic status of the patients. The ischemic status was analyzed in all 19 patients according to those stages preoperatively and postoperatively. RESULTS: Among the 19 patients, nine (47.4%) showed improvement in the regional cerebral ischemic status, six (31.6%) showed no change, and four (21.1%) showed deterioration. Both improvement and no change in the regional cerebral ischemic status were regarded as effective, while deterioration was regarded as ineffective, meaning that 15 (78.9%) patients were effective and four (21.1%) patients were ineffective. The effective rate for moyamoya disease (one of ten, 90.0%) was significantly higher than that for occlusive cerebrovascular disease (three of nine, 66.7%). Postoperatively, only one patient (case N11) exhibited deterioration of symptoms, which presented as right hemiplegia and aphasia, and no obvious changes in symptoms were observed for the other patients in the transient period. CONCLUSIONS: This study has shown that STA-MCA bypass is an effective and safe way to improve the regional cerebral perfusion and ischemic status in ischemic cerebrovascular diseases. The stage based on the regional cerebral microcirculatory change and presentation of CTP can directly reflect the pathological mechanism underlying the regional cerebral ischemic status.

[Studying change of regional cerebral blood flow after superficial temporal artery-middle cerebral artery anastomosis during acute stage in patients with Moyamoya disease].

OBJECTIVE: To explore the changes of regional cerebral blood flow at the site of anastomosis of superficial temporal artery-middle cerebral artery (STA-MCA) to guide the preventive treatment of symptomatic hyperperfusion. METHODS: A total of 35 patients with Moyamoya disease were recruited from Beijing Tiantan Hospital. There were 22 males and 13 females with an average age of 29 years (range: 5 - 55). And there were 10 children. Regional cortical blood flow (rCBF) was measured by Laser Doppler flowmeter (LDF) before, after and at Day 1, 2, 3, 4, 5 and 6 postoperation of STA-MCA anastomosis. The probe of LDF was implanted adjacent to the area of anastomosis for 144 hours to record the values of rCBF. RESULTS: The baseline LDF values of cortical rCBF near the area of anastomosis were (69 ± 24) PU before anastomosis, (66 ± 74) PU immediately after anastomosis, (123 ± 23) PU at the conscious time after anesthesia postoperation, (297 ± 17) PU at Day 1 postoperation. And the LDF values of the following 5 days were (302 ± 31), (317 ± 26), (272 ± 46), (363 ± 54) and (367 ± 24) PU respectively. CONCLUSION: As a safe and effective treatment for Moyamoya disease, STA-MCA anastomosis has great risks for symptomatic hyperperfusion. The highest risk time for hyperperfusion is identified after STA-MCA.

[Experience of 97 patients with moyamoya disease: long-term follow-up at a single center].

OBJECTIVE: To explore the medium and long-term outcomes of patients with Moyamoya disease (MD) undergoing surgery and conservative treatment at a single institution and analyze the related prognostic factors. METHODS: A retrospective review was conducted for 97 MD patients at Beijing Tiantan Hospital from January 2000 to December 2007. They were divided into 3 groups according to treatments: superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis (n = 31), indirect vascular revascularization group (n = 38) and conservative treatment group (n = 28). The primary follow-up events included death, recurrent cerebral hemorrhage, new cerebral infarction and transient ischemic attack (TIA). RESULTS: All were available for analysis with the complete follow-up data. The average follow-up period of was 85 ± 38 months. In total, there were 6 deaths with all-cause mortality (6.1%). Among them, 5 (5.1%) patients died from recurrent cerebral hemorrhage. And 17 episodes of rebleeding occurred in 11 patients. Two episodes of intracranial hemorrhage were found in 4 patients. The risk of rebleeding was 17.5%. In the STA-MCA group, 23(74%) cases had excellent recovery, 5 cases fared worse and there was no death case. Among the patients undergoing indirect vascular revascularization, 28 cases recovered favorably, 4 cases progressed and 3 cases died. In the conservative treatment group, 17 patients recovered favorably, 7 progressed, 9 experienced 15 episodes of rebleeding and 3 died. Multivariate Cox regression analysis showed that the method of treatment was an independent prognostic factor for MD and surgical revascularization was superior to conservative treatment. No correlation was found between the patient age, gender, familial history, unilateral or bilateral and prognosis (P > 0.05). Kaplan-Meier stroke risk analysis showed the risk of recurrent hemorrhage in the revascularization surgery group was lower than that in the conservative group. And no difference existed between STA-MCA and indirect arterial anastomoses. CONCLUSIONS: Rebleeding is a major cause of poor prognosis, mobility and mortality in MD patients. Surgical revascularization offers better long-term outcomes than conservative treatment. And direct arterial anastomoses may decrease recurrent hemorrhage effectively.

[Correlations of angio-architectural factors with cerebral arteriovenous malformation hemorrhage].

OBJECTIVE: To explore the relationship between angio-architectures of cerebral arteriovenous malformations (AVM) and hemorrhage. METHODS: A total of 55 consecutive surgical cases of AVM were collected in August 2010 to May 2011 at Beijing Tiantan Hospital. There were 34 males and 21 females with an average age of 32.5 years (range: 3 - 59). The initial symptoms included bleeding (n = 20), epilepsy (n = 21), headache (n = 7), neurological dysfunctions (n = 6) and others (n = 1). The relationship between size, location, type of feeding artery, type of draining vein, complicated venous aneurysm and hemorrhage was analyzed by single factor test. RESULTS: The cases of AVM fed by perforators, located in basal ganglia and post-cranial fossa, with small size, exclusively deep drainage and complicated venous aneurysm were more likely to present with hemorrhage. CONCLUSION: The hemorrhage of AVM is significantly correlated with many factors, such as the type of feeding artery, size and location of AVM, the type of draining vein and complicated venous aneurysm. But the number of draining vein is irrelevant.

Quantitative angiographic haemodynamic evaluation of bypasses for complex aneurysms: a preliminary study.

OBJECTIVE: Open microsurgery, often with bypass techniques, is indispensable for complex aneurysms. To date, it remains unknown whether arterial anatomy or quantitative blood flow measurements can predict insufficient flow-related stroke (IRS). The present study aimed to evaluate the risk factors for IRS in patients treated with open microsurgery with bypass procedures for complex internal carotid artery aneurysms. METHODS: Patients with complex aneurysms undergoing bypass surgery were retrospectively reviewed. The recipient/donor flow index (RDFI) was preoperatively evaluated using colour-coding angiography. RDFI was defined as the ratio of the cerebral blood volume of the recipient and donor arteries. The sizes of the recipient and donor arteries were measured. The recipient/donor diameter index (RDDI) was then calculated. IRS was defined as the presence of new postoperative neurological deficits and infarction on postoperative CT scans. We assessed the association between RDFI and other variables and the IRS. RESULTS: Twenty patients (38±12 years) were analysed. IRS was observed in 12 patients (60%). Patients with postoperative IRS had a higher RDFI than those without postoperative IRS (p<0.001). RDDI was not significantly different between patients with and without IRS (p=0.905). Patients with RDFI >2.3 were more likely to develop IRS (p<0.001). CONCLUSION: Quantitative digital subtraction angiography enables preoperative evaluation of cerebral blood volume. RDFI >2.3, rather than RDDI, was significantly associated with postoperative IRS. This preoperative evaluation allows appropriate decisions regarding the treatment strategy for preventing postoperative IRS.

Grading scale based on arcuate fasciculus segmentation to predict postoperative language outcomes of brain arteriovenous malformations.

OBJECTIVE: The long-term postoperative language outcomes for brain arteriovenous malformations (bAVMs) have not been well characterised. With fibres scattered in the Broca's, Wernicke's and Geschwind's area, the arcuate fasciculus (AF) is considered as a crucial structure of language function. This study aimed to observe the language outcomes, determine the risk factors and construct a grading system for long-term postoperative language deficits (LDs) in patients with bAVMs involving the AF (AF-bAVMs). METHODS: We retrospectively reviewed 135 patients with AF-bAVMs. Based on the course of the AF and our clinical experience, three boundary lines were drawn to divide the AF into segments I, II, III and IV in spatial order from the frontal lobe to the temporal lobe. Surgery-related LD evaluations were performed 1 week (short term) and at the last follow-up (long term) after surgery. Finally, based on multivariable logistic regression analysis, a grading system was constructed to predict long-term postoperative LD. The predictive accuracy was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: Sixty-two (45.9%) patients experienced short-term postoperative LD. After a mean follow-up of 50.2±24.9 months, long-term LD was found in 14 (10.4%) patients. Nidus size (p=0.007), LD history (p=0.009) and segment II involvement (p=0.030) were independent risk factors for short-term LD. Furthermore, segment II involvement (p=0.002), anterior choroidal artery (AChA) feeding (p=0.001), patient age (p=0.023) and LD history (p=0.001) were independent risk factors for long-term LD. A grading system was developed by combining the risk factors for long-term LD; its predictive accuracy was 0.921. CONCLUSIONS: The involvement of the trunk of the AF between Broca's area and the inferior parietal lobule, a nidus supplied by the AChA, older patient age and history of LD were associated with long-term postoperative LD. The grading system combining these factors demonstrated favourable predictive accuracy for long-term language outcomes.