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.

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.

Optimal Preclinical Conditions for Using Adult Human Multipotent Neural Cells in the Treatment of Spinal Cord Injury.

Stem cell-based therapeutics are amongst the most promising next-generation therapeutic approaches for the treatment of spinal cord injury (SCI), as they may promote the repair or regeneration of damaged spinal cord tissues. However, preclinical optimization should be performed before clinical application to guarantee safety and therapeutic effect. Here, we investigated the optimal injection route and dose for adult human multipotent neural cells (ahMNCs) from patients with hemorrhagic stroke using an SCI animal model. ahMNCs demonstrate several characteristics associated with neural stem cells (NSCs), including the expression of NSC-specific markers, self-renewal, and multi neural cell lineage differentiation potential. When ahMNCs were transplanted into the lateral ventricle of the SCI animal model, they specifically migrated within 24 h of injection to the damaged spinal cord, where they survived for at least 5 weeks after injection. Although ahMNC transplantation promoted significant locomotor recovery, the injection dose was shown to influence treatment outcomes, with a 1 × 106 (medium) dose of ahMNCs producing significantly better functional recovery than a 3 × 105 (low) dose. There was no significant gain in effect with the 3 × 106 ahMNCs dose. Histological analysis suggested that ahMNCs exert their effects by modulating glial scar formation, neuroprotection, and/or angiogenesis. These data indicate that ahMNCs from patients with hemorrhagic stroke could be used to develop stem cell therapies for SCI and that the indirect injection route could be clinically relevant. Moreover, the optimal transplantation dose of ahMNCs defined in this preclinical study might be helpful in calculating its optimal injection dose for patients with SCI in the future.

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.

Gamma Knife Radiosurgery for ARUBA-Eligible Patients with Unruptured Brain Arteriovenous Malformations.

BACKGROUND: A randomized trial of unruptured brain arteriovenous malformations (ARUBA) reported superior outcomes in conservative management compared to interventional treatment. There were numerous limitations to the study. This study aimed to investigate the efficacy of gamma knife radiosurgery (GKS) for patients with brain arteriovenous malformations (AVMs) by comparing its outcomes to those of the ARUBA study. METHODS: We retrospectively reviewed ARUBA-eligible patients treated with GKS from June 2002 to September 2017 and compared against those in the ARUBA study. AVM obliteration and hemorrhage rates, and clinical outcomes following GKS were also evaluated. RESULTS: The ARUBA-eligible cohort comprised 264 patients. The Spetzler-Martin grade was Grade I to II in 52.7% and III to IV in 47.3% of the patients. The mean AVM nidus volume, marginal dose, and follow-up period were 4.8 cm³, 20.8 Gy, and 55.5 months, respectively. AVM obliteration was achieved in 62.1%. The annual hemorrhage rate after GKS was 3.4%. A stroke or death occurred in 14.0%. The overall stroke or death rate of the ARUBA-eligible cohort was significantly lower than that of the interventional arm of the ARUBA study (P < 0.001) and did not significantly differ from that of the medical arm in the ARUBA study (P = 0.601). CONCLUSION: GKS was shown to achieve a favorable outcome with low procedure-related morbidity in majority of the ARUBA-eligible patients. The outcome after GKS in our patients was not inferior to that of medical care alone in the ARUBA study. It is suggested that GKS is rather superior to medical care considering the short follow-up duration of the ARUBA study.

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.

Optimized Clump Culture Methods for Adult Human Multipotent Neural Cells.

Adult human multipotent neural cell (ahMNC) is a candidate for regeneration therapy for neurodegenerative diseases. Here, we developed a primary clump culture method for ahMNCs to increase the efficiency of isolation and in vitro expansion. The same amount of human temporal lobe (1 g) was partially digested and then filtered through strainers with various pore sizes, resulting in four types of clumps: Clump I > 100 µm, 70 µm < Clump II < 100 µm, 40 µm < Clump III < 70 µm, and Clump IV < 40 µm. At 3 and 6 days after culture, Clump II showed significantly higher number of colonies than the other Clumps. Moreover, ahMNCs derived from Clump II (ahMNCs-Clump II) showed stable proliferation, and shortened the time to first passage from 19 to 15 days, and the time to 1 × 108 cells from 42 to 34 days compared with the previous single-cell method. ahMNCs-Clump II had neural differentiation and pro-angiogenic potentials, which are the characteristics of ahMNCs. In conclusion, the novel clump culture method for ahMNCs has significantly higher efficiency than previous techniques. Considering the small amount of available human brain tissue, the clump culture method would promote further clinical applications of ahMNCs.

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.

Early rebleeding of intracranial dural arteriovenous fistulas after an intracranial hemorrhage.

BACKGROUND: The aim of this study was to evaluate the clinical and angiographic characteristics of dural arteriovenous fistulas (DAVF) presenting with intracranial hemorrhage (ICH), with a focus on early rebleeding according to the initial hemorrhage type. METHOD: The clinical and radiologic features of 21 dAVFs that presented with intracranial hemorrhage were retrospectively reviewed. The hemorrhage type was classified as pure intraparenchymal hemorrhage (pIPH) and subarachnoid or subdural hemorrhage with IPH (non-pIPH). RESULTS: There were 13 patients with pIPH and 8 with non-pIPH. The median follow-up period was 30 months (range, 1-116 months), and the median interval from hemorrhage to treatment was 4 days (range, 0-72 days). Rebleeding occurred in 8 (38.1%) of 21 patients. Four (50%) of eight patients with non-pIPH suffered from early rebleeding within 3 days, while there was no early rebleeding in patients with pIPH. There was a significantly higher rate of early rebleeding in the non-pIPH group (p = 0.012). Angiographically, venous ectasia (p = 0.005) and direct cortical venous drainage (dCVD) (p = 0.008) showed a significantly higher proportion in the non-pIPH group than in the pIPH group. CONCLUSIONS: DAVFs with ICH is likely to rebleed after the first hemorrhage. Thus, early treatment can be needed in all DAVFs with ICH. In addition, DAVFs that presenting with non-pIPH and containing venous ectasia or dCVD on initial angiography may have a higher risk of early rebleeding. Therefore, cautious attention and urgent treatment are necessary for these 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.

Morphological risk factors for the rupture of anterior communicating artery aneurysms: the significance of fenestration.

INTRODUCTION: The purpose of this study was to evaluate morphological factors associated with rupture in anterior communicating artery (AcomA) aneurysms and to investigate the significance of AcomA fenestration as a risk factor for aneurysm rupture. METHODS: The clinical and radiologic findings of 255 patients with AcomA aneurysms treated with coil embolization between January 2005 and March 2014 were retrospectively reviewed. We performed univariate and multivariate analyses to evaluate the associations between morphological variables and rupture status. RESULTS: The number of patients with AcomA fenestration was 17 out of 255 (6.6 %). There were no statistically significant differences between the fenestration group and non-fenestration group in clinical and morphological characteristics. Multivariate logistic regression tests showed that superior direction of aneurysm dome (OR 2.802, p = 0.023), presence of a bleb (OR 5.998, p < 0.001), high aspect ratio (OR 3.138, p = 0.009), size greater than 7 mm (OR 3.356, p = 0.013), and AcomA fenestration (OR 4.135, p = 0.026) were significantly associated with AcomA aneurysm rupture. CONCLUSIONS: The results of this study demonstrated that a fenestrated AcomA is associated with risk of aneurysm rupture. Therefore, AcomA fenestration can be considered as an important morphological risk factor for rupture, along with other known risk factors such as the direction of aneurysm dome, a bleb, high aspect ratio, and size.

Safety and efficacy of antiplatelet response assay and drug adjustment in coil embolization: a propensity score analysis.

INTRODUCTION: The purpose of this study was to explore the safety and efficacy of an antiplatelet response assay and drug adjustment to prevent delayed thromboembolic events after stent-assisted coil embolization. METHODS: A total of 370 patients were enrolled in this study between December 2005 and July 2014. Of these, 124 patients were placed into the drug resistance test (DRT) group with drug adjustment according to response to an antiplatelet agent, and 246 patients comprised the control group with a standard antiplatelet regimen. The response to the antiplatelet agent was evaluated with the VerifyNow Rapid Platelet Function Assay. Propensity score matching analysis was performed with one-to-multiple matching. RESULTS: Among 370 patients, delayed thromboembolic events occurred in 28 (7.6 %) patients including 25 (10.2 %) in the control group and three (2.4 %) in the DRT group. Antiplatelet response test (p = 0.012), diabetes mellitus (DM) (p = 0.014), and hypertension (HTN) (p < 0.001) were associated with delayed infarction in multivariate analysis. In propensity score matching analysis, 331 patients were matched (control group (n = 229) vs. DRT group (n = 103)), and antiplatelet response (hazard ratio 0.247, 95 % confidence interval 0.070-0.868, p = 0.029) was correlated with delayed infarction. Conversely, the two groups were not significantly different with regard to total (p = 0.368) or major hemorrhagic complications (p = 0.108). CONCLUSION: Antiplatelet drug adjustment according to the results of an antiplatelet response assay might be associated with a decreased risk of delayed thromboembolic infarction compared with the standard antiplatelet regimen.

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.

Spontaneous angiographic changes in venous drainage patterns related to symptom changes in patients with untreated cavernous sinus dural arteriovenous fistula.

INTRODUCTION: We evaluated the relationship between symptomatic and angiographic changes in untreated cavernous sinus dural arteriovenous fistulas (CSdAVFs), focusing on venous drainage patterns. METHODS: The clinical and radiologic features of 34 cases of untreated CSdAVF were retrospectively reviewed. We classified venous drainage patterns as type I (only antegrade drainage), type II (combined antegrade drainage and venous reflux), type III (venous reflux without antegrade drainage), or type IV (stasis or occlusion of venous reflux). Symptom changes were categorized as improvement, aggravation of initial symptoms, or symptom pattern change. RESULTS: Twenty-one patients (61 %) showed symptom changes during follow-up (median, 12; range, 3-151 months). In the symptom improvement group (n = 10), patients who underwent follow-up angiography (n = 4) exhibited spontaneous occlusion. In the symptom aggravation group (n = 4), new venous reflux developed in 2 patients (type I to type II) and spontaneous occlusion in 2 patients (type III to spontaneous occlusion). In the symptom pattern change group (n = 7), 2 patients showed new venous reflux (type I to type II), and 5 showed stasis or occlusion of an engorged ophthalmic vein (type II or III to type IV). Angiographic regression was observed in all type III and IV patients, and cortical venous reflux (CVR) developed in 1 type I patient. CONCLUSION: Symptom changes correlated with chronological angiographic changes. Without treatment, most CSdAVFs behaved benignly and had a low incidence of CVR. Therefore, close observation is a possible protocol for managing CSdAVFs that have tolerable symptoms, no CVR, and no antegrade drainage despite aggravation or fluctuation in symptoms.

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.

Coronary heart disease in moyamoya disease: are they concomitant or coincidence?

The purpose of this study was to determine the prevalence and characteristics of symptomatic coronary heart disease (CHD) in patients with moyamoya disease (MMD). This retrospective study evaluated 456 patients who received examination for MMD between 1995 and 2012. We reviewed the patients' medical history and coronary imaging, including conventional coronary angiography and coronary computed tomography angiogram (CTA). Among 456 patients with MMD, 21 (4.6%) patients were found to have symptomatic CHD. Ten patients were treated with coronary artery bypass graft or percutaneous coronary intervention for unstable angina or myocardial infarction. Eleven were treated with medication for stable angina (n = 6) and variant angina with mild degree of stenosis (n = 5).The median age of these patients was 44 yr (range, 27-59). The median Framingham score at diagnosing MMD was < 1% (range, < 1%-16%). The old age was associated with CHD in uni- and multivariate analyses (P = 0.021, OR, 1.053; 95% CI, 1.008-1.110). Considering low age of onset and low stroke risk factor, CHD might be a systemic manifestation that is clinically relevant to MMD.

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.

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.

Evaluation of the Significance of Persistent Remnant Filling and Enlargement After Flow Diversion for Intracranial Aneurysms.

BACKGROUND: This study aimed to evaluate the clinical course after flow diversion (FD) treatment with a focus on aneurysms with remnant sac filling, by analyzing angiographic outcomes, aneurysm volume, and clinical events. METHODS: We retrospectively reviewed the medical records of 61 patients who underwent FD for intracranial aneurysms between July 2014 and June 2021. RESULTS: The majority of aneurysms (52.5%) were located in the internal carotid artery, with a median diameter of 16.6 mm and neck size of 9.3 mm. Remnant filling was observed in 17 aneurysms (27.9%) more than 18 months after FD, 10 (16.4%) of these aneurysms underwent enlargement, which occurred only in cases with subtotal filling or entry remnant states. Eleven patients experienced major adverse events, and three exhibited unfavorable functional outcomes. The incidence of major adverse events and unfavorable functional outcomes was significantly higher in the aneurysm enlargement group than that in the no-filling or stable remnant filling groups (P < 0.001). Aneurysmal diameter and the presence of incorporated branches were independent predictors of aneurysm enlargement, while the presence of incorporated branches was the only independent predictor of persistent remnant filling. CONCLUSIONS: Aneurysm enlargement after FD is not uncommon, particularly when the aneurysm is large, has incorporated vessels, or does not undergo occlusion within 12 months, often culminating in major adverse events and unfavorable functional outcomes. In addition to investigating angiographic results, it is necessary to evaluate the changes in aneurysm size and clinical events when assessing the efficacy of FD.