Early clinical experience of using the Surpass Evolve flow diverter in the treatment of intracranial aneurysms.

PURPOSE: Here, we presented our early experience with flow diversion procedures using the Surpass Evolve flow diverter (SE, Stryker) and reported the feasibility and safety profile compared to those of a control group treated with other types of flow diverters. METHODS: We included 31 and 53 consecutive flow diversion procedures performed using the SE and other commercial flow diverters, respectively, to treat intracranial aneurysms at our institution. We used two commercial flow diversion systems in the comparison group: the pipeline embolization device and Surpass Streamline. RESULTS: In the SE group, technical failures occurred in three (9.7%) cases, due to either incomplete wall apposition (n = 1, 3.2%) or stent migration (n = 2, 6.5%). Major complications occurred in four (12.9%) cases: delayed rupture of the target aneurysm (n = 1, 3.2%), major ischemic stroke (n = 1, 3.2%), sudden death from an unidentified cause (n = 1, 3.2%), and parent artery occlusion with stent thrombosis (n = 1, 3.2%). Balloon angioplasty was performed in eight (25.8%) cases. On post-procedure MRI, a DWI-positive lesion was detected in three (9.7%) cases. After multivariate adjustment, the SE group was independently associated with less procedural time of ≥ 90 min (adjusted OR, 0.09; 95% CI, 0.03-0.29; p < 0.001), balloon angioplasty (adjusted OR, 0.22; 95% CI, 0.07-0.75; p = 0.015), and DWI-positive lesions (adjusted OR, 0.04; 95% CI, 0.01-0.19; p < 0.001). CONCLUSION: The SE is safe and easy to deploy.

Improvement of Biological Effects of Root-Filling Materials for Primary Teeth by Incorporating Sodium Iodide.

Therapeutic iodoform (CHI3) is commonly used as a root-filling material for primary teeth; however, the side effects of iodoform-containing materials, including early root resorption, have been reported. To overcome this problem, a water-soluble iodide (NaI)-incorporated root-filling material was developed. Calcium hydroxide, silicone oil, and NaI were incorporated in different weight proportions (30:30:X), and the resulting material was denoted DX (D5~D30), indicating the NaI content. As a control, iodoform instead of NaI was incorporated at a ratio of 30:30:30, and the material was denoted I30. The physicochemical (flow, film thickness, radiopacity, viscosity, water absorption, solubility, and ion releases) and biological (cytotoxicity, TRAP, ARS, and analysis of osteoclastic markers) properties were determined. The amount of iodine, sodium, and calcium ion releases and the pH were higher in D30 than I30, and the highest level of unknown extracted molecules was detected in I30. In the cell viability test, all groups except 100% D30 showed no cytotoxicity. In the 50% nontoxic extract, D30 showed decreased osteoclast formation compared with I30. In summary, NaI-incorporated materials showed adequate physicochemical properties and low osteoclast formation compared to their iodoform-counterpart. Thus, NaI-incorporated materials may be used as a substitute for iodoform-counterparts in root-filling materials after further (pre)clinical investigation.

Gamma Knife Radiosurgery for Incidental, Symptomatic Unruptured, and Ruptured Brain Arteriovenous Malformations.

BACKGROUND: This study was performed to investigate clinical characteristics and outcome after gamma knife radiosurgery (GKS) in patients with incidental, symptomatic unruptured, or ruptured arteriovenous malformations (AVMs). METHODS: A total of 491 patients with brain AVMs treated with GKS from June 2002 to September 2017 were retrospectively reviewed. All patients were classified into the incidental (n = 105), symptomatic unruptured (n = 216), or ruptured AVM (n = 170) groups. RESULTS: The mean age at diagnosis of incidental, symptomatic unruptured, and ruptured AVMs was 40.3, 36.7, and 27.6 years, respectively. The mean nidus volume was 3.9, 5.7, and 2.4 cm3, respectively. Deep venous drainage was identified in 34, 54, and 76% patients, respectively. There were no significant differences in obliteration rates after GKS between the 3 groups (64.8, 61.1, and 65.9%, respectively) after a mean follow-up period of 60.5 months; however, patients with incidental AVM had a significantly lower post-GKS hemorrhage rate than patients with symptomatic unruptured or ruptured AVMs (annual hemorrhage rate of 1.07, 2.87, and 2.69%; p = 0.028 and p = 0.049, respectively). CONCLUSIONS: There is a significant difference in clinical and anatomical characteristics between incidental, symptomatic unruptured, and ruptured AVMs. The obliteration rate after GKS is not significantly different between the 3 groups. Meanwhile, an older age at diagnosis and lower hemorrhage rate after GKS in incidental AVMs suggest that they have a more indolent natural course with a lower life-long risk of hemorrhage.

Clinical Role of Microembolic Signals in Adult Moyamoya Disease With Ischemic Stroke.

Background and Purpose- Hemodynamic compromise has been implicated in moyamoya disease (MMD) with transient ischemic attacks or ischemic stroke. However, increasing evidence supports the notion that artery-to-artery embolism may also contribute to ischemic events based on microembolic signal (MES) monitoring. Methods- A total of 48 patients aged between 20 and 60 years with newly diagnosed MMD were enrolled and angiographically classified according to the Suzuki staging system. For detection of MESs, transcranial Doppler was performed at the middle cerebral artery bilaterally for a 30-minute period. Mean flow velocities in the middle cerebral artery were also evaluated and categorized into low (<40 cm/s), normal (40-80 cm/s), and high (>80 cm/s). Clinical characteristics, cerebral angiography findings, recent ischemic events within 3 months, and antiplatelet medication were correlated with transcranial Doppler findings. Results- MESs were detected in 11 of the 48 patients (23%), with a frequency of 11 of 89 (12%) examined hemispheres. The mean number of MESs was 2 (range, 1-6). Six of the 11 hemispheres (55%) presented with ischemic strokes or transient ischemic attacks, and 2 (18%) presented with hemorrhagic strokes. The presence of MESs was associated with recent ischemic events ( P=0.024) and high mean flow velocities ( P=0.016), which was usually observed in Suzuki stage I and II (early-stage MMD). After controlling for age, sex, and antiplatelet medication, both recent ischemic events (odds ratio, 6.294; 95% CI, 1.345-29.457; P=0.019) and high mean flow velocities (odds ratio, 6.172; 95% CI, 1.235-31.25; P=0.027) were found to be independent predictors of MESs. Conclusions- MESs were observed in patients with high mean flow velocities, particularly early-stage MMD, and clinically associated with recent ischemic events. A randomized controlled study is necessary to determine the efficacy of antiplatelet agents in the treatment of MES-positive MMD.

Cav-1 (Caveolin-1) and Arterial Remodeling in Adult Moyamoya Disease.

Background and Purpose- Moyamoya disease (MMD) is a unique cerebrovascular occlusive disease characterized by progressive stenosis and negative remodeling of the distal internal carotid artery (ICA). We hypothesized that cav-1 (caveolin-1)-a protein that controls the regulation of endothelial vesicular trafficking and signal transduction-is associated with negative remodeling in MMD. Methods- We prospectively recruited 77 consecutive patients with MMD diagnosed via conventional angiography. Seventeen patients with intracranial atherosclerotic stroke and no RNF213 mutation served as controls. The outer distal ICA diameters were examined using high-resolution magnetic resonance imaging. We evaluated whether the degree of negative remodeling in the patients with MMD was associated with RNF213 polymorphism, cav-1 levels, or various clinical and vascular risk factors. We also investigated whether the derived factor was associated with negative remodeling at the cellular level using the tube formation and apoptosis assays. Results- The serum cav-1 level was lower in the patients with MMD than in the controls (0.47±0.29 versus 0.86±0.68 ng/mL; P=0.034). The mean ICA diameter was 2.48±0.98 mm for the 126 affected distal ICAs in patients with MMD and 3.84±0.42 mm for the asymptomatic ICAs in the controls ( P<0.001). After adjusting for confounders, cav-1 levels (coefficient, 1.018; P<0.001) were independently associated with the distal ICA diameter in patients with MMD. In vitro analysis showed that cav-1 downregulation suppressed angiogenesis in the endothelial cells and induced apoptosis in the smooth muscle cells. Conclusions- Our findings suggest that cav-1 may play a major role in negative arterial remodeling in MMD.

Infarct Pattern and Collateral Status in Adult Moyamoya Disease: A Multimodal Magnetic Resonance Imaging Study.

BACKGROUND AND PURPOSE: Moyamoya disease (MMD) is a unique cerebrovascular disease characterized by the progressive stenosis of large intracranial arteries and a hazy network of basal collaterals, called moyamoya vessels. Although hemodynamic studies have been applied in MMD patients, the mechanisms of stroke in MMD are still unclear. The present study evaluated the infarct pattern and collateral status using multimodal magnetic resonance imaging in MMD patients. METHODS: Adult MMD patients with acute ischemic stroke were prospectively recruited, and infarct pattern on diffusion-weighted imaging was evaluated. A collateral flow map, derived from magnetic resonance perfusion-weighted imaging data, was generated through automatic postprocessing, and collateral status was assigned into 3 grades. Transcranial Doppler monitoring was performed to detect microembolic signals in selected patients. RESULTS: A total of 67 hemispheres (31 patients with bilateral and 5 patients with unilateral MMD) were analyzed. Most patients (83.7%) showed embolic pattern and rarely deep (9.3%) or hemodynamic infarct pattern (7.0%) on diffusion-weighted imaging. Most cases (86%) showed good collateral status, and few patients with acute infarcts of embolic pattern showed poor collateral status (n=7). One third (31.6%) of patients who underwent transcranial Doppler monitoring showed microembolic signals. CONCLUSIONS: In the studied population of adult MMD patients, embolic phenomenon played an important role in ischemic stroke. Therapeutic strategies against thromboembolism, as well as collateral enhancing strategies targeting improvement of hemodynamic status or increased washout of emboli, are warranted.

Preventive Effect of Clazosentan against Cerebral Vasospasm after Clipping Surgery for Aneurysmal Subarachnoid Hemorrhage in Japanese and Korean Patients.

BACKGROUND: Clazosentan has been explored worldwide for the prophylaxis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). In a dose-finding trial (CONSCIOUS-1) conducted in Israel, Europe, and North America, clazosentan (1, 5, and 15 mg/h) significantly reduced the incidence of cerebral vasospasm, but its efficacy in Japanese and Korean patients was unknown. We conducted a double-blind comparative study to evaluate the occurrence of cerebral vasospasm in Japanese and Korean patients with aSAH. METHODS: The aim of this multicenter, double-blind, randomized, placebo-controlled, dose-finding phase 2 clinical trial, was to evaluate the efficacy, pharmacokinetics, and safety of clazosentan (5 and 10 mg/h) against cerebral vasospasm after clipping surgery in Japanese and Korean patients with aSAH. Patients aged between 20 and 75 years were administered the study drug within 56 h after the aneurysm rupture and up to day 14 post-aSAH. The incidence of vasospasm, defined as an inner artery diameter reduction of major intracranial arteries ≥34% based on catheter angiography, was compared between each treatment group. Cerebral infarction due to vasospasm at 6 weeks and patients' outcome at 3 months was also compared. RESULTS: Among 181 enrolled patients, 158 completed the study and were analyzed. The incidence of vasospasm up to day 14 after aSAH onset was 80.0% in the placebo group (95% CI 67.0-89.6), 38.5% in the 5 mg/h clazosentan group (95% CI 25.3-53.0), and 35.3% in the 10 mg/h clazosentan group (95% CI 22.4-49.9), indicating that the incidence of vasospasm was significantly reduced by clazosentan treatment (placebo vs. 5 mg/h clazosentan, p < 0.0001; placebo vs. 10 mg/h clazosentan, p < 0.0001). The occurrence of cerebral infarction due to vasospasm was 20.8% in the placebo group (95% CI 10.8-34.1), 3.8% in the 5 mg/h clazosentan group (95% CI 0.5-13.2), and 4.2% in the 10 mg/h clazosentan group (95% CI 0.5-14.3), indicating that clazosentan significantly reduced the occurrence of cerebral infarctions caused by vasospasm (placebo vs. 5 mg/h clazosentan, p = 0.0151; placebo vs. 10 mg/h clazosentan, p = 0.0165). The overall incidence of all-cause death and/or vasospasm-related morbidity/mortality was significantly reduced in the 10 mg/h clazosentan group compared with the placebo group (p = 0.0003). CONCLUSION: These results suggest that clazosentan prevents cerebral vasospasm and subsequent cerebral infarction, and could thereby improve outcomes after performing a clipping surgery for aSAH in Japanese and Korean patients.

Clinical Features of Superficially Located Brain Arteriovenous Malformations with Transdural Arterial Communication.

BACKGROUND: Contrary to deeply located brain arteriovenous malformations (AVMs), superficially located AVMs are more likely to have transdural arterial communications (TACs). However, the clinical and radiologic characteristics of patients presenting with AVMs and TACs are poorly understood. The purpose of this study is to determine whether clinicoradiological features of cerebral AVMs differ according to TAC. METHODS: Between 2002 and 2012, 438 consecutive patients with a brain AVM were treated in our hospital. Among them were 124 patients with superficially located brain AVMs who met the inclusion and exclusion criteria of our study. We retrospectively reviewed the clinicoradiological features of their TACs to explore the variation in characteristics. RESULTS: Thirty-two of the 124 patients with a superficially located AVM (25.8%) had TAC. Radiologic findings of brain AVM images with TAC showed that TAC occurred significantly more frequently among larger AVMs (with vs. without TAC, 11.2 vs. 4.0 ml) and among diffuse AVMs (56.3 vs. 28.3%, p = 0.004). Clinical findings indicate that TAC was associated with chronic headache (43.8 vs. 12.0%, p < 0.001) and older age (43.1 vs. 36.6 years, p = 0.037). CONCLUSIONS: Brain AVM with TAC seems to be accompanied by distinctive clinical features, such as chronic headache and older age. Larger size and diffuseness of the AVM were also associated with TAC. Findings from this study and the prognostic significance of TAC should be further explored in a large prospective study.

Examination of endothelial cell-induced epidermal regeneration in a mice-based chimney wound model.

As wound contraction in the cutaneous layer occurs rapidly in mice, mechanical means are typically used to deliberately expose the wound to properly investigate healing by secondary intention. Previously, silicon rings and splinting models were attempted to analyze histological recovery but prevention of surrounding epidermal cell migration and subsequent closure was minimal. Here, we developed an ideal chimney wound model to evaluate epidermal regeneration in murine under hESC-EC transplantation through histological analysis encompassing the three phases of regeneration: migration, proliferation, and remodeling. Human embryonic stem cell derived endothelial cells (hESC-EC) were transplanted due to possessing a well-known therapeutic effect in angiogenesis which also enhances epidermal repair to depict the process of regeneration. Following a standard 1 mm biopsy punch, a chimney manufactured by modifying a 1.7 mL microtube was simply inserted into the excisional wound to complete the modeling process. Under this model, the excisional wound remained fully exposed for 14 days and even after 4 weeks, only a thin transparent layer of epidermal tissue covered the wound site. This approach is able to more accurately depict epidermal repair in relation to histology while also being a user-friendly and cost-effective way to mimic human recovery in rodents and evaluate epithelial repair induced by a form of therapy.

Determinants of Basal Collaterals in Moyamoya Disease: Clinical and Genetic Factors.

BACKGROUND/AIMS: To enable the diagnosis of moyamoya disease (MMD), detection of distal internal carotid artery stenosis and hazy network of basal collaterals (BCs) are required. This study aimed at evaluating the factors that could determine the degree of BCs in patients with angiographically confirmed MMD. METHODS: We analyzed 146 consecutive patients with MMD (age 26.2 ± 19.6, range 1-75). The degree of BCs (%) was measured based on conventional angiography. Factors associated with the degree of BCs, including clinico-radiological and genetic factors (p.Arg4810Lys variant), were analyzed. RESULTS: The degree of BCs varied among MMD patients and significantly decreased with an increase in the age of diagnosis of MMD (coefficient -1.55; p < 0.001). Although the degree of BC development depends on the MMD stage (Suzuki stage), it is less prominent in adult-onset (>18 years) MMD compared to childhood MMD. The presence of p.Arg4810Lys variant, types of MMD (bilateral vs. unilateral) and stroke (ischemic, hemorrhagic, or asymptomatic), shrinkage (outer diameter) of intracranial vessels, external carotid collateral status, and cortical neovascularization were not associated with the degree of BCs. CONCLUSION: Although prominent BCs are required for diagnosis of MMD, BCs are decreased with aging, suggesting that angiogenic capacity is altered in adult onset MMD compared to childhood MMD.

Whole genome sequencing of an ethnic Pathan (Pakhtun) from the north-west of Pakistan.

BACKGROUND: Pakistan covers a key geographic area in human history, being both part of the Indus River region that acted as one of the cradles of civilization and as a link between Western Eurasia and Eastern Asia. This region is inhabited by a number of distinct ethnic groups, the largest being the Punjabi, Pathan (Pakhtuns), Sindhi, and Baloch. RESULTS: We analyzed the first ethnic male Pathan genome by sequencing it to 29.7-fold coverage using the Illumina HiSeq2000 platform. A total of 3.8 million single nucleotide variations (SNVs) and 0.5 million small indels were identified by comparing with the human reference genome. Among the SNVs, 129,441 were novel, and 10,315 nonsynonymous SNVs were found in 5,344 genes. SNVs were annotated for health consequences and high risk diseases, as well as possible influences on drug efficacy. We confirmed that the Pathan genome presented here is representative of this ethnic group by comparing it to a panel of Central Asians from the HGDP-CEPH panels typed for ~650 k SNPs. The mtDNA (H2) and Y haplogroup (L1) of this individual were also typical of his geographic region of origin. Finally, we reconstruct the demographic history by PSMC, which highlights a recent increase in effective population size compatible with admixture between European and Asian lineages expected in this geographic region. CONCLUSIONS: We present a whole-genome sequence and analyses of an ethnic Pathan from the north-west province of Pakistan. It is a useful resource to understand genetic variation and human migration across the whole Asian continent.

Well-defined differentiation of hESC-derived hemangioblasts by embryoid body formation without enzymatic treatment.

Human hemangioblasts exist only during the early embryonic developmental stage thereby limiting the adult cellular source from which to obtain such cells for study. To overcome this, hemangioblast studies have focused on utilizing human embryonic stem cell (hESC) derivatives but current methods are cell-line dependent. Single cell dissociation of a hESC colony quickly led to cell death in most hESC lines due to enzyme treatment which, in turn, reduced induction potential and hemangioblast differentiation efficiency. Therefore, we sought to effectively improve the process of cell dissociation that is adaptable to various hESC lines and increase the initial induction potential of embryoid body (hEB). As a result, we determined an effective cell dissociation method through a comparison study involving various reagents which demonstrated successful dissociation regardless of cell line and enhanced hemangioblast differentiation efficiency.

Treatment outcomes of surgical clipping for unruptured anterior circulation aneurysm-single institute experiences in the era of neurophysiologic monitoring and endovascular treatment.

Recently, the treatment of intracranial aneurysms entered a new phase due to safe surgical tool such as neurophysiologic monitoring and challenged by endovascular treatment. To determine the safety of clipping surgery in the modern era, we reviewed our experiences of simple unruptured anterior circulation aneurysm surgery which is commonly performed in many places. We retrospectively reviewed 610 consecutive patients who were treated with surgical clipping under motor evoked potential (MEP) monitoring for a tiny to large anterior circulation aneurysm in a single institute between 2008 and 2012. MEP changes were identified in 40 cases (6.6 %). MEP deterioration was associated with remote site epidural hematoma (n = 1), anesthesia (n = 2), temporary clipping (n = 21), and permanent clipping (n = 16). Despite that no persistent MEP deterioration was noted after prompt corrective measures, 56 (9.2 %) patients showed symptomatic (n = 14) and asymptomatic (n = 42) radiologic abnormalities. Anterior cerebral artery (ACA) aneurysm was associated with a higher radiologic complication rate (Fisher's exact test, P < 0.05). Two (0.3 %) patients showed severe morbidity (mRS >2) at latest follow-up. MEP monitoring can be helpful in preventing postoperative motor deterioration but seems to have some limitations. Although the permanent morbidity rate was low, a significant clinical (2.3 %) or radiologic (9.2 %) abnormality rate was identified even in simple aneurysm clipping that should be taken into account when performing interdisciplinary treatment planning and patient counseling. Also, direct vascular monitoring or new neurophysiologic monitoring techniques are needed to reduce surgical complications, especially in ACA aneurysm surgery.

Unilateral intracranial arteriopathy in pediatric stroke: course, outcome, and prediction of reversible arteriopathy.

BACKGROUND AND PURPOSE: The nonprogressive, often reversible, unilateral arteriopathy known as transient (focal) cerebral arteriopathy has become a leading cause of childhood arterial ischemic stroke. However, it is not a well-recognized arteriopathy in East Asian countries where moyamoya disease is prevalent. METHODS: We retrospectively reviewed 74 children and adolescents (<18 years) with arterial ischemic stroke and intracranial arteriopathy to identify 29 patients with unilateral large-artery arteriopathy mainly in the anterior circulation. Among them, 25 patients who fulfilled the following inclusion criteria were analyzed to determine the angiographic course and outcome: (1) repeated vascular imaging at least twice and (2) absence of thrombotic disorders or cardiac diseases. RESULTS: The course of unilateral arteriopathy was classified as reversible in 17 patients (68%), progressive in 5 (20%), and stable in 3 (12%). Nine of the 17 patients with reversible arteriopathy exhibited initial worsening of the arteriopathy mostly within 1 month, but the worsened arteriopathy began to improve within 3 months and continued to improve even after a few years. Two of these 9 patients experienced stroke progression at 6 days. Of the variables analyzed, infarction involving the basal ganglia (15 of 17) and arterial beading on angiography performed within 2 weeks (10 of 12) were associated with reversible arteriopathy. Involvement of the ipsilateral posterior cerebral artery was rare (1 of 17). CONCLUSIONS: The possibility of reversible arteriopathy should be suspected in children and adolescents presenting with arterial ischemic stroke and unilateral arteriopathy.

High-resolution magnetic resonance wall imaging findings of Moyamoya disease.

BACKGROUND AND PURPOSE: Diagnosis of Moyamoya disease (MMD) is based on the characteristic angiographic findings. However, differentiating MMD from intracranial atherosclerotic disease (ICAD) is difficult. We compared vessel wall imaging findings on high-resolution magnetic resonance imaging between MMD and ICAD. METHODS: High-resolution magnetic resonance imaging was performed on 32 patients with angiographically proven MMD and 16 patients with acute infarcts because of ICAD. Bilateral internal carotid arteries and steno-occlusive middle cerebral artery were analyzed for wall enhancement and remodeling. RESULTS: Enhancement patterns and distribution were different. Most patients with MMD (90.6%) showed concentric enhancement on distal internal carotid arteries and middle cerebral arteries, whereas focal eccentric enhancement was observed on the symptomatic segment in ICAD. MMD was characterized by middle cerebral artery shrinkage; the remodeling index and wall area were lower in MMD than in ICAD (remodeling index, 0.19±0.11 versus 1.00±0.43; wall area, 0.32±0.22 versus 6.00±2.72; P<0.001). CONCLUSIONS: MMD was characterized by concentric enhancement on bilateral distal internal carotid arteries and shrinkage of middle cerebral artery, regardless of symptoms.

Identification of the rare compound heterozygous variants in the NEB gene in a Korean family with intellectual disability, epilepsy and early-childhood-onset generalized muscle weakness.

We examined a Korean family with complex phenotypes characterized by intellectual disability, epilepsy and early-childhood-onset generalized muscle weakness. Since we did not find any abnormality using several conventional genetic tests for detection of chromosomal aberrations, gene copy number variations and mitochondrial gene mutations, we aimed to identify disease-causing genetic alteration(s) in this family. We conducted whole-exome sequencing (WES) in this family. After filtering the WES data, we compared five exome sequences of two affected siblings, one unaffected sibling and the unaffected parents, and we determined the allele frequency of the identified variants in an Asian population. Finally, we selected one candidate variant pair which is unique in the patients and corresponds to an autosomal recessive genetic model. The two affected siblings had the same compound heterozygous variation in the NEB gene encoding nebulin, which was composed of two different missense variants: c.2603T>C (p.L868P) in exon 27 and c.21340C>T (p.R7114W) in exon 143. We confirmed these variations by Sanger sequencing. On the basis of the fundamental role of nebulin in the brain and skeletal muscles, we concluded that this compound heterozygous NEB variation may be a sound candidate for the disease-causing mutation in this family. Since the patients are characterized by generalized muscle weakness together with neurodevelopmental phenotypes, it is suggested that NEB mutations could manifest more diverse phenotypes than those previously described.

Clinical course of asymptomatic adult moyamoya disease.

BACKGROUND: As regular medical check-ups are becoming more common, the prevalence of asymptomatic moyamoya disease (MMD) is increasing. However, the definition and clinical features are still unclear. The lack of precision has hampered the establishment of guidelines for the management of asymptomatic MMD. The purpose of this study was to define and clarify the clinical characteristics of asymptomatic MMD in adults. METHODS: We identified all adults (aged ≥18 years) with MMD who underwent digital subtraction angiography or magnetic resonance angiography at our institution from 1995 through 2010. The authors defined asymptomatic MMD as asymptomatic or nonspecific symptom without any infarction or ischemia on magnetic resonance imaging. In our MMD registry, 40 patients (74 hemispheres) were identified and enrolled in this retrospective cohort study. Their demographic, radiological and clinical findings were evaluated. The log-rank test was used to assess prognostic factors. Pearson's correlation test and the Mann-Whitney U test were used to identify correlation angiographic staging and age or perfusion status. RESULTS: Overall, 6 patients underwent indirect bypass surgery and 36 received antiplatelet medication. On initial single positron emission tomography (35 patients, 67 affected hemispheres), basal and acetazolamide stress brain perfusion were decreased in 19 (28.4%) and 22 (32.8%) hemispheres, respectively. Among 70 angiographically evaluated hemispheres, 6 were unilateral MMD; 27 of 64 affected hemispheres (42.2%) had transdural collateral at evaluation. Age (p = 0.309, Pearson's correlation test) and hemodynamic impairment (p = 0.614, Mann-Whitney U test) did not correlate with angiographic staging. During a median 32-month (range 6-203) clinical follow-up, 3 nonsurgically treated patients had a transient ischemic attack, which was associated with decreased vascular reserve (p < 0.001, log-rank test) and smoking (p = 0.017). Other variables did not show a significant association with clinical progression. During a median 24-month (range 12-108) radiological follow-up, 3 patients displayed angiographic progression and 3 displayed new hemodynamic abnormalities. Radiological progressions were related to hypertension only (p = 0.022). In this case series, there was no case of ischemic or hemorrhagic stroke. CONCLUSION: The findings suggest that asymptomatic MMD in adults is not a stable disease in our definition. However, stroke rate (0%) was lower than previous reports. Lifestyle modification, stroke risk factor control and/or antiplatelet medication seem to be appropriate initial treatments for patients with normal cerebrovascular reserve. A clear definition of asymptomatic MMD and further clarification of its clinical course are needed to set precise treatment guidelines.

Neovascularization precedes occlusion in moyamoya disease: angiographic findings in 172 pediatric patients.

BACKGROUND: Both basal collaterals (BC) and cortical microvascularization (CM) on angiography have been suggested as moyamoya disease (MMD)-specific findings; however, it is unknown whether the vascular network represents compensatory mechanisms for vascular occlusion or aberrant active neovascularization. METHODS: We investigated the grade of antegrade MCA flow, the degree of BC, and the presence of CM on conventional angiography in relation to disease severity in pediatric MMD. CM was defined as enlarged and winding distal cortical arteries and categorized into anterior or posterior CM depending on their sources. Findings from basal and acetazolamide stress brain perfusion SPECT studies were also evaluated. RESULTS: A total of 172 pediatric patients with MMD were enrolled in this study. As the severity of MMD increased, the grade of antegrade MCA flow gradually diminished. While the degree of BC peaked at Suzuki stage 3-4, CM was frequently observed at early MMD stages. About two-thirds of hemispheres with normal antegrade MCA flow on angiography and normal perfusion status on SPECT had anterior and/or posterior CM. Both anterior and posterior CM gradually decreased with the advancement of MMD. CONCLUSION: Our findings from a large cohort of angiographically confirmed pediatric MMD patients indicate that neovascularization may occur before significant hemodynamic impairment in MMD.

Endovascular Embolization of Intracranial Aneurysms Using Target Tetra Detachable Coils: Angiographic and Clinical Results from a Single Center.

Background/Objectives: Target tetra detachable coils (TTDCs) aid in achieving effective framing during the coil embolization of small intracranial aneurysms by maintaining a tetrahedral conformation within the aneurysm sac. We aimed to report the initial experience of patients treated for intracranial aneurysms using TTDCs, with a specific focus on efficacy and safety. Methods: We retrospectively reviewed the medical records of 41 patients who underwent the coil embolization of intracranial aneurysms sized ≤10 mm with TTDCs between April and May 2023. Post-procedural angiographic and clinical results were reviewed. Results: Of the 46 aneurysms (45 unruptured and 1 ruptured), 33 (71.7%) were treated with the stent-assisted technique and 13 (28.3%) using the simple coil embolization technique. Post-procedural angiography showed complete occlusion in 41 aneurysms (89.1%), neck remnants in 1 (2.2%), and residual aneurysms in 4 (8.7%). The mean packing density was 34.7% (19.3-46.8%), with TTDC coil length comprising a mean of 88.5% of the total coil length. No major device- or procedure-related complications were observed. During the follow-up, 40 aneurysms (93.0%) demonstrated complete occlusion, while neck remnants were observed in 1 (2.3%), and residual aneurysms in 2 (4.7%). No cases of recanalization were observed. Conclusions: The TTDC is a safe and effective device for the endovascular treatment of intracranial aneurysms. Follow-up studies are required to establish long-term results.

Flow Diversion for Cerebral Aneurysms: A Decade-Long Experience with Improved Outcomes and Predictors of Success.

BACKGROUND: Flow diversion has significantly improved the management of cerebral aneurysms. Technological advancements and increased clinical experience over the past decade have led to better outcomes and fewer complications. This study provides updated results and examines the factors that influence the success of flow diversion. METHODS: We reviewed records of 115 patients with 121 intracranial aneurysms treated from July 2014 to August 2023. All patients had unruptured aneurysms in the anterior and posterior circulation. RESULTS: Complete aneurysm occlusion was achieved in 72.7% of cases, with a complication rate of 9.1%. Significant predictors of complete occlusion included aneurysm diameter (OR = 0.89, 95% CI 0.82-0.97, p = 0.009) and the presence of incorporated branches (OR = 0.22, 95% CI 0.08-0.59, p = 0.003). Cox analysis identified neck diameter (HR = 0.92, 95% CI 0.87-0.98, p = 0.009) and incorporated branch (HR = 0.40, 95% CI 0.24-0.69, p = 0.001) as significant for occlusion. Multivariable analysis identified aneurysm diameter (OR = 1.21, 95% CI 1.09-1.37, p = 0.001) as significant for safety outcomes. Improved outcomes were observed in recent treatments, with higher occlusion rates (79.7% vs. 61.7%, p = 0.050) and lower complication rates (4.1% vs. 14.9%, p = 0.011). CONCLUSIONS: Enhanced technical proficiency, better devices, and refined patient selection have significantly improved the efficacy and safety of flow diversion for cerebral aneurysms. Identifying significant predictors for treatment success and safety outcomes can inform clinical practice, aiding in patient selection.