Hemorrhagic Moyamoya Disease Research Articles

Proteomic Profiling of Exosomes From Hemorrhagic Moyamoya Disease and Dysfunction of Mitochondria in Endothelial Cells.

Moyamoya disease (MMD) is a rare steno-occlusive and slowly progressing cerebrovascular disorder. The detailed mechanism of the underlying pathogenesis is still blurry. Tandem Mass Tag-labeled quantitative proteomics was performed on serum-derived exosomes (SDEs) extracted from adult patients diagnosed with pure ischemic MMD or hemorrhagic MMD and healthy controls. Then mouse brain vascular endothelial cell (EC), human umbilical vein EC, neuroblastoma cell, and human hepatocyte cell were treated with exosomes, and changes of the protein expression in mouse brain vascular EC cells were identified. Proteomics analysis results showed that 859 shared proteins were detected in SDEs from ischemic and hemorrhagic MMD patients with 231 differently expressed compared with healthy controls. Bioinformatic analysis revealed dysregulated cell growth and maintenance and indicated disturbed actin dynamics in MMD, with CFL1 (Cofilin-1) and ACTR2/3 (actin-related protein 2/3; also known as ARP2/3) downregulated in ischemic and hemorrhagic patients’ SDEs. We also found immunity dysfunction in hemorrhagic MMD. Following treatment with MMD SDEs, mouse brain vascular EC cells showed significantly higher levels of proliferation and more ethynyl-2-deoxyuridine-positive cells compared with the healthy control group, while there were no obvious changes in the human umbilical vein EC and human hepatocyte cell. Interestingly, we also found that SDEs from ischemic MMD promoted neuroblastoma cell proliferation. Proteomic analysis of mouse brain vascular EC cells suggested that SDEs from hemorrhagic MMD patients induced dysfunction of the mitochondria in cerebrovascular ECs. This study highlighted potential molecular mechanisms underlying the pathogenesis of MMD patients, thereby providing new therapeutic strategies for MMD.

Surgical Treatment of Adult Moyamoya Disease In Saudi Arabia: A Review Article

Moyamoya disease (MMD) is an isolated chronic, usually bilateral, vasculopathy disease of undetermined etiology. The clinical presentations of MMD include TIA, ischemic stroke, hemorrhagic stroke, seizures, headache, and cognitive impairment. Intra- and extra-cranial revascularization for the prevention of recurrence of bleeding in patients with hemorrhagic MMD is controversial. Surgical revascularization of MMD includes 3 types: Direct revascularization, indirect revascularization and combined revascularization. The surgical goal of cerebral revascularization is to prevent progression of symptomology, alleviate intracranial hemodynamic stress, and reduce the incidence of subsequent ischemic or hemorrhagic stroke. However, surgical treatments pose various complications due to the sudden increase in cerebral blood flow or hemodynamic changes caused by perioperative risk factors and anesthesia, such as HS, cerebral hemorrhage and cerebral infarction, bypass occlusion caused by distal vascular resistance, bypass occlusion caused by compression of the temporalis, and anastomotic aneurysm.

Association of intracranial vessel wall enhancement and cerebral hemorrhage in moyamoya disease: a high-resolution magnetic resonance imaging study.

This study aimed to investigate the enhancement characteristics of vessel wall in patients with moyamoya disease (MMD) using 3D high-resolution magnetic resonance (MR) imaging and their relationship with initial and recurrent intracranial hemorrhage. Consecutive patients with MMD were retrospectively analyzed and classified as intracranial hemorrhagic and non-hemorrhagic groups according to the CT or MR images. The clinical features and vessel wall characteristics were compared between the two groups. Logistic regression was performed to relate the vessel wall characteristics to the initial hemorrhage in MMD patients. Patients in hemorrhagic group were followed up after surgery to evaluate the relationship between vessel wall characteristics and recurrent hemorrhage. A total of 507 MMD patients including 79 hemorrhagic and 428 non-hemorrhagic MMD patients were recruited in the study. We found that hemorrhagic group had more patients with vessel wall enhancements (40.5% vs. 25.7%, p = 0.009) and more eccentric enhanced lesions (17.7% vs. 6.5%, p = 0.001) compared to those in non-hemorrhage group and vessel wall enhancements were independently associated with ipsilateral initial hemorrhage after adjusted for clinical factors (OR = 1.99, CI 1.20-3.28, p = 0.007). Furthermore, three recurrent intracranial hemorrhagic episodes in the present study were all observed in MMD patients with vessel wall enhancement during the long-term follow-up after surgery. Wall enhancement of intracranial vessels was significantly associated with intracranial hemorrhage in MMD patients. Our findings suggest that vessel wall enhancement may serve as a marker of intracranial hemorrhage.

Delayed Anastomotic Occlusion after Direct Revascularization in Adult Hemorrhagic Moyamoya Disease.

Delayed anastomotic occlusion occurred in a considerable proportion of hemorrhagic moyamoya disease (MMD) patients undergoing direct revascularization. This study aimed to investigate the predictors and outcomes of delayed anastomotic occlusion in adult hemorrhagic MMD. The authors retrospectively reviewed 87 adult hemorrhagic MMD patients. Univariate and multivariate logistic regression analyses were performed. After an average of 9.1 ± 6.9 months of angiographic follow-up, the long-term graft patency rates were 79.8%. The occluded group had significantly worse angiogenesis than the non-occluded group (p < 0.001). However, the improvement of dilated anterior choroidal artery–posterior communicating artery was similar (p = 0.090). After an average of 4.0 ± 2.5 years of clinical follow-up, the neurological statues and postoperative annualized rupture risk were similar between the occluded and non-occluded groups (p = 0.750; p = 0.679; respectively). In the multivariate logistic regression analysis, collateral circulation Grade III (OR, 4.772; 95% CI, 1.184–19.230; p = 0.028) and preoperative computed tomography perfusion (CTP) Grade I–II (OR, 4.129; 95% CI, 1.294–13.175; p = 0.017) were independent predictors of delayed anastomotic occlusion. Delayed anastomotic occlusion in adult hemorrhagic MMD might be a benign phenomenon. Good collateral circulation (Grade III) and compensable preoperative intracranial perfusion (CTP Grade I–II) are independent predictors for this phenomenon. Moreover, the delayed anastomotic occlusion has no significant correlations with the long-term angiographic and neurological outcomes, except neoangiogenesis.

Intralateral and Perilateral Ventricular Arteries on Original Axial Magnetic Resonance Angiography in Adult Moyamoya Disease

Background: Patients with moyamoya disease often develop cerebral infarction and hemorrhage, but the ischemic and hemorrhagic subtypes are difficult to diagnose prior to disease onset. We aimed to differentiate the ischemic and hemorrhagic subtypes of moyamoya disease by analyzing the intralateral and perilateral ventricular arteries on the original axial magnetic resonance angiography (MRA) images. Methods: We retrospectively analyzed the intralateral and perilateral ventricular arteries on the original axial time-of-flight (TOF)-MRA images of 18 patients with hemorrhagic moyamoya disease, 25 patients with ischemic moyamoya disease, and 22 control patients with unruptured aneurysms. Results: There were significantly more intralateral and perilateral ventricular arteries on the original axial MRA images in the patients with hemorrhagic moyamoya disease (6.3 ± 2.7) than in those with ischemic moyamoya disease (0.8 ± 0.9) and those with unruptured aneurysms (0.4 ± 0.8). Conclusion: The intralateral and perilateral ventricular arteries on the original axial TOF-MRA images might suggest the hemorrhagic type of moyamoya disease prior to onset.

Changes in Brain Functional Network Connectivity in Adult Moyamoya Diseases.

The online version contains supplementary material available at (10.1007/s11571-021-09666-1).

Validation of choroidal anastomosis on high-resolution magnetic resonance imaging as an imaging biomarker in hemorrhagic moyamoya disease.

This study aimed to investigate the association between dilation and proliferation and anastomosis of perforating arteries, and intracranial hemorrhage in moyamoya disease (MMD) patients, using high-resolution magnetic resonance imaging (HRMRI). Adult patients with MMD at advanced stages were prospectively enrolled and underwent HRMRI exams. Dilation and proliferation of the lenticulostriate artery (LSA), medullary artery, and anterior or posterior choroidal arteries (AChA or PChA) were assessed. Abnormal anastomoses were identified between (1) the LSA and the medullary or insular arteries; (2) the thalamo-geniculate, thalamo-tuberal, or thalamo-perforating arteries and the medullary or insular arteries; and (3) the AChA or PChA and the medullary or insular arteries. The association between these variables and hemorrhagic events was calculated using univariate and multivariate analyses. Fifty patients (14 men; mean age, 35.4 ± 9.7 years) were finally analyzed, including 17 hemorrhagic patients and 33 non-hemorrhagic patients. The inter-rater agreement for the qualitative evaluation of perforating arteries was good. Dilation and proliferation of the AChA or PChA (88.2% versus 54.5%, p = 0.027), and choroidal anastomosis (64.7% versus 18.2%, p = 0.002) were more frequently observed in patients with hemorrhage. Multivariate logistic regression showed that choroidal anastomosis remained significantly associated with hemorrhage (odds ratio = 5.95, 95% confidence interval = 1.21-29.25, p = 0.028). Choroidal anastomosis is independently associated with hemorrhagic events in adult patients with MMD at advanced stages. HRMRI can provide detailed information on both the anatomies and abnormal collaterals in MMD, which facilitates risk estimates of bleeding in MMD. • High-resolution magnetic resonance imaging allows for the evaluation of perforating arteries in patients with moyamoya disease. • Choroidal anastomosis is associated with hemorrhagic events in patients with moyamoya disease. • High-resolution magnetic resonance imaging might facilitate further grading and classification of moyamoya vessels.

Flow-augmentation bypass for moyamoya disease

Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease with unknown etiology, which is characterized by progressive steno-occlusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network formation at the base of the brain. MMD has an intrinsic temporal nature to attempt a gradual conversion of the vascular supply for the brain from intracranial/internal carotid (IC) system to extracranial/external carotid (EC) system, so called "IC-EC conversion." Compatible cerebrovascular angio-architecture could be found in association with a variety of conditions such as neuro-fibromatosis type-1, Down's syndrome and cranial irradiation, which is called as moyamoya syndrome, akin/quasi MMD, or secondary MMD. Diagnosis of moyamoya vasculopathy, either idiopathic or secondary, is clinically important because flow-augmentation bypass is markedly beneficial for this entity to prevent cerebral ischemic attack by improving cerebral blood flow. Moreover, recent evidence indicated that flow-augmentation bypass could prevent re-bleeding in hemorrhagic MMD patients. Based on these backgrounds, there is a worldwide increase in the number of MMD patients undergoing bypass surgery. We sought to demonstrate our standard surgical procedure of superficial temporal artery-middle cerebral artery bypass with indirect pial synangiosis for MMD and its technical pitfall. We also discuss the intrinsic peri-operative hemodynamics of MMD after bypass surgery, including local cerebral hyper-perfusion and characteristic hemodynamic ischemia caused by watershed shift phenomenon. The aim of this review article is to understand the basic pathology of MMD, which is essential for complication avoidance while conducting flow-augmentation bypass for MMD.

Recognition of moyamoya disease and its hemorrhagic risk using deep learning algorithms: sourced from retrospective studies.

Although intracranial hemorrhage in moyamoya disease can occur repeatedly, predicting the disease is difficult. Deep learning algorithms developed in recent years provide a new angle for identifying hidden risk factors, evaluating the weight of different factors, and quantitatively evaluating the risk of intracranial hemorrhage in moyamoya disease. To investigate whether convolutional neural network algorithms can be used to recognize moyamoya disease and predict hemorrhagic episodes, we retrospectively selected 460 adult unilateral hemispheres with moyamoya vasculopathy as positive samples for diagnosis modeling, including 418 hemispheres with moyamoya disease and 42 hemispheres with moyamoya syndromes. Another 500 hemispheres with normal vessel appearance were selected as negative samples. We used deep residual neural network (ResNet-152) algorithms to extract features from raw data obtained from digital subtraction angiography of the internal carotid artery, then trained and validated the model. The accuracy, sensitivity, and specificity of the model in identifying unilateral moyamoya vasculopathy were 97.64 ± 0.87%, 96.55 ± 3.44%, and 98.29 ± 0.98%, respectively. The area under the receiver operating characteristic curve was 0.990. We used a combined multi-view conventional neural network algorithm to integrate age, sex, and hemorrhagic factors with features of the digital subtraction angiography. The accuracy of the model in predicting unilateral hemorrhagic risk was 90.69 ± 1.58% and the sensitivity and specificity were 94.12 ± 2.75% and 89.86 ± 3.64%, respectively. The deep learning algorithms we proposed were valuable and might assist in the automatic diagnosis of moyamoya disease and timely recognition of the risk for re-hemorrhage. This study was approved by the Institutional Review Board of Huashan Hospital, Fudan University, China (approved No. 2014-278) on January 12, 2015.

Different subtypes of collateral vessels in hemorrhagic moyamoya disease with p.R4810K variant

BackgroundThe aim of this study was to investigate the hemorrhgic sites and collateral vessels in hemorrhagic MMD with the p.R4810K variant.MethodsHemorrhage sites were classified as either anterior or posterior. Collateral vessels were classified into three subtypes according to origin: lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis. Hemorrhage sites and collateral vessels were compared between patients with wild-type p.R4810K variant (GG) and patients with heterozygous p.R4810K variant (GA) after 1:1 propensity score matching.ResultsA total of 130 hemorrhagic MMD patients were included in present study, 21 pairs (42 hemorrhagic hemispheres) were obtained after 1:1 propensity score. In GA group, 16 hemispheres (76.2%) presented anterior hemorrhage, and 5 hemispheres (23.8%) presented with posterior hemorrhage. In GG group, 13 hemispheres (61.9%) presented anterior hemorrhage, and 8 hemispheres (38.1%) presented with posterior hemorrhage. No significant differences were found in hemorrhagic sites between two matched groups (P > 0.05). Of 21 hemispheres in GA group, 10 (47.6%) exhibited lenticulostriate anastomosis, 6 (28.6%) thalamic anastomosis, and 6 (28.6%) choroidal anastomosis. Of 21 hemispheres in GG group, 3 (14.3%) exhibited lenticulostriate anastomosis, 5 (23.8%) thalamic anastomosis, and 9 (42.9%) choroidal anastomosis. There was significant difference in lenticulostriate anastomosis between two matched groups (P = 0.045). After adjustment the age, sex, and PCA involvement, we found that lenticulostriate anastomosis was associated with p.R4810K variant (OR, 5.995; 95% CI, 1.296–27.737; P = 0.022).ConclusionLenticulostriate anastomosis might be associated with p.R4810K variant. Whereas hemorrhagic sites, thalamic anastomosis, and choroidal anastomosis might not be associted withp.R4810K variant.

Postoperative Functional Outcomes and Prognostic Factors in Two Types of Adult Moyamoya Diseases

BackgroundTo determine the functional outcomes in each period for adult ischemic and hemorrhagic Moyamoya disease (MMD) patients and identify prognostic factors. MethodsThe current retrospective study reviewed consecutive adult MMD patients surgically treated from January 2012 to June 2017. Perioperative clinical data were collected and follow-up was conducted via telephone interviews. Functional outcomes and prognostic factors were analyzed. ResultsA total of 219 ischemic MMD patients (268 hemispheres) and 157 hemorrhagic patients (193 hemispheres) were included. The median follow-up time was 18 months (3–69 months). MMD type had no significant effect on the modified Rankin Scale(mRS) score at discharge. Perioperative complications (P = 0.004) and the mRS score at baseline (P < 0.001) were risk factors correlated with the short-term functional outcomes in both groups, while diabetes mellitus (DM, P = 0.022) also played a role in the ischemic group. During the follow-up period, functional outcomes obviously improved in both groups, but two groups showed nonproportional cumulative curves for favorable functional outcomes (log-rank test, P = 0.483). Stroke recurrence (P < 0.001) and mRS at discharge (P < 0.001) were common factors related with long-term functional outcomes in two types of MMD patients. Particularly, female patients with ischemic MMD were more likely to have higher mRS scores (P = 0.028) and Suzuki stage was positively associated with long-term functional outcomes in hemorrhagic group (P = 0.044). ConclusionsMMD type had no significant effect on prognosis while both types of MMD patients showed overall significant improvements in functional outcomes after surgery. Different types of MMD patients have distinct prognostic factors for short-term and long-term functional outcomes.

Clinical and Radiological Outcomes After Revascularization of Hemorrhagic Moyamoya Disease.

Objective: To evaluate clinical and radiological outcomes after revascularization of hemorrhagic moyamoya disease (MMD).Materials and Methods: We retrospectively collected patients with hemorrhagic MMD who received revascularization from January 2011 to June 2018 at a high-volume stroke center. Rebleeding, ischemic stroke, modified Rankin Scale (mRS) and death after revascularization were used to evaluate long-term clinical outcome. Poor neurological outcome was defined as a mRS>2. The changes of original and revascularization collaterals were used to evaluate radiological outcome. The clinical and radiological outcomes between patients with different surgical revascularization were compared.Results: A total of 312 patients (319 hemispheres) were recruited, including 133 hemispheres (41.7%) with indirect revascularization and 186 hemispheres (58.3%) with direct revascularization. In 308 hemispheres with clinical follow-up data, Postoperative rebleeding, ischemic stroke, poor neurological outcome and death occurred in 13.0% (40/308), 2.6% (8/308), 12.0% (37/308), and 6.2% (19/308) of the hemispheres, respectively. The rates of postoperative rebleeding (8.5 vs. 19.1%, P = 0.006) and poor neurological outcome (8.5 vs. 16.8%, P = 0.026) were lower in hemispheres with direct revascularization than those with indirect revascularization. However, there was no statistically significant difference in the rates of postoperative ischemic stroke (1.1 vs. 4.6%, P = 0.129) and death (4.5 vs. 8.4%, P = 0.162) between the two groups. Multivariate logistic regression analysis indicated that the risk of postoperative rebleeding was higher in those with untreated aneurysms, repetitive bleeding episodes, normal perfusion status, and indirect revascularization (P < 0.05). In 78 hemispheres with radiological follow-up data, the regression of moyamoya vessels, anterior choroidal artery (AchA), posterior communicating artery (PcomA) and aneurysms were present in 44.9, 47.4, 25.6, and 11.5% of the hemispheres, respectively. The regression of original collaterals and establishment of revascularization collaterals were more significant in hemispheres with direct revascularization than those with indirect revascularization (P < 0.05).Conclusion: Direct revascularization may be superior to indirect revascularization for prevention of rebleeding and poor neurological outcome in adults with hemorrhagic MMD. The risk of postoperative rebleeding was higher in those with untreated aneurysms, repetitive bleeding episodes, normal perfusion status, and indirect revascularization. The regression of original collaterals and establishment of revascularization collaterals after revascularization were more significant in hemispheres with direct revascularization than those with indirect revascularization.

Difference in periventricular anastomosis in child and adult moyamoya disease: a vascular morphology study.

Periventricular anastomosis (PA), which is a novel term for extended collateral vessels in moyamoya disease (MMD), is reportedly associated with a high risk of intracranial hemorrhage in adult patients. The present study aimed to clarify the similarities and the differences in the development of PA between three MMD groups, classified by age at the time of diagnosis and clinical phenotype. This study included 232 hemispheres of 132 patients with MMD who underwent surgical revascularization. The subjects were classified into child ischemic (CI) group, adult ischemic (AI) group, and adult hemorrhagic (AH) group. We evaluated the lenticulostriate (LSA), thalamic (THA), choroidal (ChA), anterior choroidal (AChA), and posterior choroidal (PChA) anastomosis as well as the posterior cerebral artery (PCA) involvement. The PA scores and the sums of each grade of LSA, THA, and ChA anastomosis were also calculated in all of the cases. In a multiple comparison test, the PA scores (P <0.01), LSA (P <0.01), and ChA anastomosis (P = 0.013) were more prominent in the CI than in the AI group. The PA scores (P <0.01) and LSA (P = 0.011), ChA (P <0.01), AChA (P <0.01), and PChA anastomosis (P =0.016) were more prominent in the AH group than in the AI group. The CI and AH groups showed similar characteristics except for PCA involvement. After multivariate adjustments using the AI group as a reference group, the PA scores and the positive rates of LSA and ChA anastomosis remained significantly higher in the CI and AH groups. The patterns of PA development in the CI and AH groups were similar in that they were more prominent than in the AI group. These findings may contribute to a better understanding of the progression of ischemic and hemorrhagic MMD.

Combined STA-MCA Bypass and Encephalodurosynangiosis Versus Encephalodurosynangiosis Alone in Adult Hemorrhagic Moyamoya Disease: A 5 -Year Outcome Study

Aim: The purpose of this study was to compare the 5-year prognosis of combined superficial temporal artery- middle cerebral artery (STA-MCA) bypass and Encephalodurosynangiosis (EDAS) and EDAS alone in hemorrhagic moyamoya disease (MMD). Methods: This study included 123 adult patients admitted to Beijing Tiantan Hospital with hemorrhagic MMD between 2010 and 2015. The surgical procedures included combined revascularization of STA-MCA anastomosis with EDAS (n = 79) or EDAS alone (n = 44). We recorded basic demographic data as well as several risks factors, and used multivariate regression analysis to evaluate the predictive factor of overall survival and rebleeding-free survival. Results: Of the 123 patients with hemorrhagic MMD, the mean age was 37.97 ± 11.04 years old and the mean follow-up period was 65.9 months (ranging from 12 to 100 months). A total of 21 rebleeding events occurred in 19 patients, yielding an annual incidence of rebleeding of 3.1%. Of the 19 patients with rebleeding, 11 (57.8%) patients died of rebleeding and one patient experience 3 rebleeding events. In the combined revascularization group, 9 (11.3%) patients experienced rebleeding, of which 5 (6.3%) died. This incidence was lower than in the indirect group, where 22.7% of patients experienced rebleeding events and 13.6% died. However, no significant difference was found between these 2 groups. In Kaplan-Meier survival analysis, the combined revascularization group had a better prognosis than the EDAS alone group, and multivariate regression analysis revealed that the combined revascularization procedure was associated with a better outcome. Conclusions: Both combined revascularization and EDAS alone can reduce the risk of rebleeding in hemorrhagic MMD. Combined revascularization was found to be superior to EDAS alone in terms of preventing rebleeding events.

Impact of cortical hemodynamic failure on both subsequent hemorrhagic stroke and effect of bypass surgery in hemorrhagic moyamoya disease: a supplementary analysis of the Japan Adult Moyamoya Trial.

Here, the authors aimed to determine whether the presence of cerebral hemodynamic failure predicts subsequent bleeding attacks and how it correlates with the effect of direct bypass surgery in hemorrhagic moyamoya disease. Data from the Japanese Adult Moyamoya (JAM) Trial were used in this study: 158 hemispheres in 79 patients. A newly formed expert panel evaluated the SPECT results submitted at trial enrollment and classified the cortical hemodynamic state of the middle cerebral artery territory of each hemisphere into one of the following three groups: SPECT stage (SS) 0 as normal, SS1 as decreased cerebrovascular reserve (CVR), and SS2 as decreased CVR with decreased baseline blood flow. In the nonsurgical cohort of the JAM Trial, the subsequent hemorrhage rate during the 5-year follow-up was compared between the SS0 (hemodynamic failure negative) and SS1+2 (hemodynamic failure positive) groups. The effect of direct or combined direct/indirect bypass surgery on hemorrhage prevention was examined in each subgroup. The hemodynamic grade was SS0 in 59 (37.3%) hemispheres, SS1 in 87 (55.1%), and SS2 in 12 (7.6%). In the nonsurgical cohort, subsequent hemorrhage rates in the SS0 and SS1+2 groups were 12 cases per 1000 person-years and 67 cases per 1000 person-years, respectively. Kaplan-Meier analysis revealed that hemorrhagic events were significantly more common in the SS1+2 group (p = 0.019, log-rank test). Cox regression analysis showed that hemodynamic failure was an independent risk factor for subsequent hemorrhage (HR 5.37, 95% CI 1.07-27.02). In the SS1+2 subgroup, bypass surgery significantly suppressed hemorrhagic events during 5 years (p = 0.001, HR 0.16, 95% CI 0.04-0.57), with no significant effect in the SS0 group (p = 0.655, HR 1.56, 95% CI 0.22-11.10). Examination of effect modification revealed that the effect of surgery tended to differ nonsignificantly between these two subgroups (p = 0.056). Hemodynamic failure is an independent risk factor for subsequent hemorrhage in hemorrhagic moyamoya disease. Direct bypass surgery showed a significant preventive effect in the hemodynamically impaired hemispheres. Thus, hemodynamic failure, as well as previously proposed factors such as choroidal anastomosis, should be considered for the surgical indication in hemorrhagic moyamoya disease.Clinical trial registration no.: C000000166 (umin.ac.jp).

Cerebral Hemodynamic Changes After Revascularization in Patients With Hemorrhagic Moyamoya Disease.

Objective: To explore the cerebral hemodynamic changes after revascularization in patients with hemorrhagic moyamoya disease (MMD).Materials and Methods: We retrospectively included 57 hemorrhagic MMD patients in a high-volume stroke center from January 2016 to December 2018. All subjects were evaluated with whole-brain CT perfusion (CTP) before and after surgical revascularization. Absolute and relative CTP values in the regions of cortical middle cerebral artery territory (CMT) and deep brain area (DBA) of hemorrhagic hemispheres were measured. Differences between pre- and post-operative CTP values were assessed comprehensively. The patients were categorized into subgroups based on revascularization subtypes and postoperative CTP intervals.Results: The relative cerebral blood volume (rCBV) in DBA and CMT significantly reduced in postoperative CTP (P < 0.05). The median and interquartile range of the proportion of rCBV decrease (rCBVc%) were 7.2% (2.3–13.2%). The rCBV reduction retained statistical significant in patients who received subtypes of revascularization, and in patients with variable intervals of follow-up (P < 0.05). There was no significant difference of rCBVc% between patients who received different revascularization and among patients with different postoperative CTP intervals (P > 0.05). The relative mean transit time (rMTT) and relative time to peak (rTTP) also showed downward trends, but without retainable statistical significance in stratified analysis. There was no significant change in relative cerebral blood flow (rCBF) (P > 0.05).Conclusion: In patients with hemorrhagic MMD, the CBV appeared to decrease and be relatively stable in the chronic phase after revascularization, with varying degrees of MTT and TTP shortening. However, there was no significant change in CBF.

Functional Outcomes After Revascularization Procedures in Patients With Hemorrhagic Moyamoya Disease.

Poor natural history of hemorrhagic Moyamoya disease (MMD) is related to high rehemorrhage rates between 32% and 61%. Postrevascularization, rehemorrhage rates reportedly decrease to 12% to 17%. To evaluate long-term functional outcomes and rehemorrhage rates of hemorrhagic MMD patients treated with surgical revascularization and examine these in relation to clinical and radiological factors. Patients treated surgically for hemorrhagic MMD over a 26-yr period were identified. Modified Rankin scale (mRS) was used to assess clinical status at presentation and functional outcomes. Multivariable regression analyses were performed to evaluate the risk factors associated with rehemorrhage rates and functional outcomes. A total of 104 patients (mean age: 38.04 yr) were identified. The mean mRS score at baseline was 1.3. Of 172 revascularized hemispheres, 157 (91.3%) were direct superficial temporal artery (STA)-middle cerebral artery (MCA) bypasses and the rest indirect. Over the mean follow-up of 61.4 mo, 8 of 104 patients (7.7%) experienced rehemorrhage with rehemorrhage rate per person-years of 1.9%. A total of 4 patients died with 1 related to rehemorrhage. At the last follow-up, mean mRS score improved to 1.1. No significant risk factors were identified in relation to the rehemorrhage rates (P<.05). The patients' initial mRS score was positively associated with mRS scores at the final follow-up (P<.001). STA-MCA direct bypass was associated with better performance status (P=.033). Rehemorrhage rate following surgical revascularization of the hemorrhagic MMD patients at 7.7% is lower compared with much higher natural history rates. Surgical revascularization improved patients' performance status. These outcomes support performing revascularization procedure with a preference for direct STA-MCA bypasses.

Abstract TP487: Comprehensive Profiling of Secreted Factors in the Cerebrospinal Fluid of Moyamoya Disease Patients

Background: Moyamoya disease (MMD) is a chronic cerebrovascular disease characterized by progressive occlusion of the internal carotid arteries leading to ischemic and hemorrhagic events. The underlying pathogenesis of MMD remains unclear. In this study we investigated key secreted molecules in the cerebrospinal fluid (CSF) of MMD patients including relation to the extent of neovascularization and eventual functional outcomes. Methods: This study included intraoperative CSF collected from 32 controls (Chiari malformation and cranial nerve hyperactive syndromes) and 73 MMD patients (ischemic: 39; hemorrhagic: 34) that underwent combined direct and indirect superficial temporal artery-middle cerebral artery revascularization procedure. 62 factors were analyzed using multiplex luminex assay, including angiogenic growth factors, cytokines, and chemokines. Cellular retinoic acid binding protein (CRBP1) was also measured using ELISA. Functional outcome was assessed using the modified Rankin scale score (mRS). Matsushima criteria was used for grading the neovascularization. Results: Forty molecules were significantly elevated in both MMD subtypes in comparison with controls. The common top highly secreted CSF proteins included platelet-derived growth factor bb, chemokine ligand 5 and plasminogen activator inhibitor 1 (p&lt;0.001). CRBP1 and other growth factors such as brain-derived nerve growth factor and basic fibroblast growth factor were also elevated in both MMD subtypes (p&lt;0.01). Our results also revealed a number of proteins not previously reported in MMD. Ingenuity pathway analysis indicated that the ischemic and hemorrhagic MMD subtypes exhibited similar cellular/molecular functions and pathways including cellular activation, migration and inflammatory response. Interestingly, while neuro-inflammation and dendritic cell pathways were activated in MMD patients, lipid signaling pathways involving nuclear receptors PPAR and LXR/RXR signaling were inhibited. Conclusions: CSF analysis revealed that a number of cytokines, chemokines and growth factors are elevated in both MMD subtypes. These molecules potentially contribute to the pathogenesis of MMD and could be potential future therapeutic targets.

Anatomical features of the superficial temporal artery in hemorrhagic moyamoya disease based on CT angiography.

The superficial temporal artery (STA) is an important continuation of the external carotid artery. It is divided into the frontal branch and the parietal branch at or above the zygomatic arch. In the present study, a comparative analysis of the STA in patients with and without moyamoya disease (MMD) was performed using CT angiography. Patients admitted to our institution for spontaneous intracranial hemorrhage were potential candidates. In general, 25 cases (50 sides) in the MMD group and 25 cases (50 sides) in the non-MMD group were selected for evaluation. The morphology of the STA when crossing the zygomatic arch, the association between the STA bifurcation and the zygomatic arch, the branching characteristics of the STA, the parameters of the STA bifurcation point, the diameter of the STA and the distance from the origin of the STA to the bifurcation point were selected for analysis. There were no significant differences between the two groups with regard to the association between the STA bifurcation and the zygomatic arch, the diameter of the STA or the distance from the origin of the STA to the bifurcation point. However, the bifurcation point of the STA was closer to the posterior edge of the mandibular condyle in the patients with MMD.

Postoperative collateral formation after indirect bypass for hemorrhagic moyamoya disease

BackgroundThe research on postoperative collateral formation for hemorrhagic moyamoya disease (MMD) evaluated by using digital subtraction angiography (DSA) is limited. Our study objective was to investigate the postoperative collateral formation after indirect bypass for hemorrhagic MMD.MethodsAll consecutive inpatients with hemorrhagic MMD who received indirect bypass at Beijing Tiantan Hospital, Capital Medical University from January 2010 through December 2018 were screened. The site of the hemorrhage was classified as either anterior or posterior. Postoperative collateral formation was evaluated on lateral views using the Matsushima scale. Univariate and multivariate logistic regression analyses were carried out to determine the factors influencing postoperative collateral formation.ResultsSix-four patients (64 hemispheres) were included in this study. After a median 8.5 months DSA follow-up, 14 (21.9%) hemispheres had grade A collateral circulation, 13 (20.3%) had grade B, and 37 (57.8%) had grade C. Twenty-seven (42.2%) hemispheres had good postoperative collateral formation and 37 (57.8%) had poor postoperative collateral formation. The univariate logistic regression analyses showed that age at operation (OR, 0.954; 95% CI, 0.908–1.003; p = 0.066), hemorrhagic site (OR, 4.694; 95% CI, 1.582–13.923; p = 0.005), and PCA involvement (OR, 3.474; 95% CI, 0.922–13.086; p = 0.066) may effect postoperative collateral formation. The multivariate logistic regression analyses showed that only anterior hemorrhage (OR, 5.222; 95% CI, 1.605–16.987; p = 0.006) was significantly related to good postoperative collateral formation.ConclusionAnterior hemorrhage was significantly related to good postoperative collateral formation after indirect bypass.