Clinical Outcome of Patients with Poor-Grade Aneurysmal Subarachnoid Hemorrhage with Bundled Treatments: A Propensity Score-Matched Analysis.

BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH), defined as Hunt and Hess (HH) grades IV and V, is a challenging disease because of its high mortality and poor functional outcomes. The effectiveness of bundled treatments has been demonstrated in critical diseases. Therefore, poor-grade aSAH bundled treatments have been established. This study aims to evaluate whether bundled treatments can improve long-term outcomes and mortality in patients with poor-grade aSAH. METHODS: This is a comparative study using historical control from 2008 to 2022. Bundled treatments were introduced in 2017. We compared the rate of favorable outcomes (modified Rankin Scale score 0-2) at 6 months and mortality before and after the introduction of the bundled treatments. To eliminate confounding bias, the propensity score matching method was used. RESULTS: A total of 90 consecutive patients were evaluated. Forty-three patients received bundled treatments, and 47 patients received conventional care. The proportion of patients with HH grade V was higher in the bundle treatment group (41.9% vs. 27.7%). Conversely, the proportion of patients with fixed pupils on the initial examination was higher in the conventional group (30.2% vs. 38.3%). After 1:1 propensity score matching, 31 pairs were allocated to each group. The proportion of patients with 6-month favorable functional outcomes was significantly higher in the bundled treatments group (46.4% vs. 20.7%, p = 0.04). The 6-month mortality rate was 14.3% in the bundled treatments group and 27.3% in the conventional group (p = 0.01). Bundled treatments (odd ratio 14.6 [95% confidence interval 2.1-100.0], p < 0.01) and the presence of an initial pupil reflex (odd ratio 12.0 [95% confidence interval 1.4-104.6], p = 0.02) were significantly associated with a 6-month favorable functional outcome. CONCLUSIONS: The bundled treatments improve 6-month functional outcome and mortality in patients with poor-grade aSAH.

Extended monitoring of re-coiled cerebral aneurysms after initial postcoiling recanalization: Safety and durability of repeat coil embolization.

PURPOSE: In the endovascular era, postcoiling recanalization of cerebral aneurysms is occurring with greater frequency. Repeat coiling is usually done to prevent rebleeding, although long-term outcomes of re-embolization have yet to be adequately investigated. The present study was undertaken to assess clinical and radiographic outcomes of re-embolization in recanalized aneurysms, focusing on procedural safety, efficacy, and durability. METHOD: In this retrospective review, we examined 308 patients with 310 recurrent aneurysms. All lesions were re-coiled, once major recanalization (after initial coil embolization) was established. Medical records and radiologic data amassed during extended follow-up were then subject to review. Cox proportional hazards regression analysis was undertaken to identify risk factors for subsequent recurrence. RESULT: During a lengthy follow-up (mean, 40.2 ± 33.0 months), major recanalization developed again in 87 aneurysms (28.1%). Multivariable Cox regression analysis linked re-recanalization to initial saccular neck width (p=.003) and autosomal dominant polycystic kidney disease (ADPKD; p<.001). Stent implantation (p=.038) and successful occlusion at second coiling (p=.012) were protective against later recanalization in this setting. The more recent the second embolization was performed, the lower the risk of further recurrence (p=.023). Procedure-related complications included asymptomatic thromboembolism (n = 9), transient ischemic neurologic deficits (n = 2), procedural bleeding (n = 1), and coil migration (n = 1), but there were no residual effects or deaths. CONCLUSION: Repeat coil embolization is a safe therapeutic option for recanalized cerebral aneurysms. Wide-necked status and ADPKD emerged as risks for subsequent recanalization, whereas successful occlusion and stent implantation seemed to reduce the likelihood of recurrence after re-embolization procedures.

Genome-wide association study identifies novel susceptibilities to adult moyamoya disease.

Genome-wide association study has limited to discover single-nucleotide polymorphisms (SNPs) in several ethnicities. Here, we investigated an initial GWAS to identify genetic modifiers predicting with adult moyamoya disease (MMD) in Koreans. GWAS was performed in 216 patients with MMD and 296 controls using the large-scale Asian-specific Axiom Precision Medicine Research Array. A subsequent fine-mapping analysis was conducted to assess the causal variants associated with adult MMD. A total of 489,966 out of 802,688 SNPs were subjected to quality control analysis. Twenty-one SNPs reached a genome-wide significance threshold (p = 5 × 10-8) after pruning linkage disequilibrium (r2 < 0.8) and mis-clustered SNPs. Among these variants, the 17q25.3 region including TBC1D16, CCDC40, GAA, RNF213, and ENDOV genes was broadly associated with MMD (p = 3.1 × 10-20 to 4.2 × 10-8). Mutations in RNF213 including rs8082521 (Q1133K), rs10782008 (V1195M), rs9913636 (E1272Q), rs8074015 (D1331G), and rs9674961 (S2334N) showed a genome-wide significance (1.9 × 10-8 < p < 4.3 × 10-12) and were also replicated in the East-Asian populations. In subsequent analysis, RNF213 mutations were validated in a fine-mapping outcome (log10BF > 7). Most of the loci associated with MMD including 17q25.3 regions were detected with a statistical power greater than 80%. This study identifies several novel and known variations predicting adult MMD in Koreans. These findings may good biomarkers to evaluate MMD susceptibility and its clinical outcomes.

Geometric versus Hemodynamic Indexes for Rupture-Destined Aneurysms: A Retrospective Cohort and a Repeated-Measures Study.

INTRODUCTION: A proper stratification of intracranial aneurysms is critical in identifying rupture-destined aneurysms and unruptured intracranial aneurysms. We aimed to determine the utility of geometric and hemodynamic indexes in differentiating two types of aneurysms and to examine the characteristics of natural evolutionary changes of unruptured aneurysms. METHODS: Rupture-destined aneurysm refers to an aneurysm that undergoes subsequent aneurysmal subarachnoid hemorrhage (SAH). On the other hand, an unruptured intracranial aneurysm is characterized by an aneurysm that does not experience rupture during serial time-of-flight magnetic resonance angiography (TOF-MRA). In addition to geometric indexes, signal intensity gradient (SIG), an in vivo approximated wall shear stress from TOF-MRA, was measured in aneurysms. The difference between the maximum and minimum values of SIG in an aneurysm compared to parent arterial values was designated as the delta-SIG ratio. RESULTS: This study analyzed 20 rupture-destined aneurysms in 20 patients and 45 unruptured intracranial aneurysms in 41 patients with follow-up TOF-MRA. While geometric indexes did not show differences between the two groups, the delta-SIG ratio was higher in the rupture-destined aneurysms (1.5 ± 0.6 vs. 1.1 ± 0.3, p = 0.032). The delta-SIG ratio showed a higher area under the receiver operating characteristic curve for SAH than the size ratio (0.72 [95% CI, 0.58-0.87] vs. 0.56 [95% CI, 0.41-0.72], p = 0.033). The longitudinal re-examination of TOF-MRA in the unruptured intracranial aneurysms revealed evidence of aneurysmal growth, while concurrently exhibiting hemodynamic stability. CONCLUSION: The delta-SIG ratio showed higher discriminatory results between the two groups compared to geometric indexes. Aneurysmal rupture risk should be assessed by considering both geometric and hemodynamic information. This study was registered on ClinicalTrials.gov (NCT05450939).

Population-Attributable Risk Fractions for Antiplatelets and Anticoagulants in Spontaneous Intracranial Hemorrhages.

INTRODUCTION: Concerns about spontaneous intracranial hemorrhages (sICHs) have increased over time with the increasing use of antithrombotic agents. Hence, we aimed to analyze the risk and risk fractions for antithrombotics in sICHs in South Korea. METHODS: From the National Health Insurance Service-National Sample Cohort including 1,108,369 citizens, 4,385 cases, aged 20 years or more and newly diagnosed as sICHs between 2003 and 2015, were included in this study. A total of 65,775 sICH-free controls were randomly selected at a ratio of 1:15 from individuals with the same birth year and sex according to a nested case-control study design. RESULTS: Although the incidence rate of sICHs started to decrease from 2007 onward, the use of antiplatelets, anticoagulants, and statins continued to increase. Antiplatelets (adjusted odds ratio [OR] 3.59, 95% confidence interval [CI] 3.18-4.05), anticoagulants (adjusted OR 7.46, 95% CI 4.92-11.32), and statins (adjusted OR 1.98, 95% CI 1.79-2.18) were significant risk factors for sICHs even after adjusting for hypertension, alcohol intake, and cigarette smoking. From 2003-2008 to 2009-2015, the population-attributable fractions changed from 28.0% to 31.3% for hypertension, from 2.0% to 3.2% for antiplatelets, and from 0.5% to 0.9% for anticoagulants. CONCLUSION: Antithrombotic agents are significant risk factors for sICHs, and their contribution is increasing over time in Korea. These findings are expected to draw the attention of clinicians to precautions to be taken when prescribing antithrombotic agents.

Delayed ischemic events with low-dose prasugrel medication for stent-assisted coil embolization in intracranial aneurysm patients.

OBJECTIVE: Much emphasis has been put on the use of antiplatelet medication for the prevention of ischemic events in the treatment of cerebral aneurysms with stent assistance. In this regard, the effectiveness and safety of a low-dose prasugrel regimen during the periprocedural period was recently reported. The purpose of this study was to present the outcomes of patients on low-dose prasugrel regimens during the follow-up period after stent-assisted coil embolization (SACE) of cerebral aneurysms. METHODS: For the 396 consecutive patients undergoing SACE procedures, low-dose prasugrel therapy (5 mg of prasugrel and 100 mg of aspirin) was recommended for 3 months after the endovascular treatment. The authors performed a retrospective review of a single-center experience focusing on delayed ischemic events beyond 1 month after treatment. The mean follow-up period was 24.6 ± 11.3 months. RESULTS: In this cohort of patients on a low-dose prasugrel regimen, cerebral infarction occurred in 1 patient (0.3%, 95% CI 0%-1.8%) beyond 1 month after SACE. No intracranial hemorrhage occurred. Overall ischemic events occurred in 14 patients (3.5%, 95% CI 2.1%-5.9%), all within 6 months of the coiling procedure. All patients had transient symptoms. The events occurred within 2 months after cessation of prasugrel in 11 patients (78.6%). Prasugrel maintenance for 6 months was found to result in lower ischemic events compared with maintenance for 3 months. CONCLUSIONS: For patients undergoing SACE, a low-dose prasugrel regimen was a safe and reliable treatment option for the prevention of delayed ischemic events. Transient ischemic events often occurred within 2 months of stopping prasugrel medication.

Is it safe to discontinue antiplatelet medication after stent-assisted coil embolization? If so, when is the best time?

PURPOSE: Antiplatelet maintenance after stent-assisted coil embolization (SACE) is generally considered essential to avoid post-procedural thromboembolic complications. However, there is still debate as to whether it is safe to discontinue antiplatelet drugs after SACE or when is the best time to do so. We investigate herein the clinical outcomes experienced by patients who discontinue antiplatelet agents after SACE. METHODS: From a prospective database, we retrieved the data for 120 consecutive patients (harboring 130 aneurysms) in whom antiplatelet agents were discontinued after SACE between January 2010 and December 2019. We defined thromboembolic complications associated with discontinuation as neurologic or radiographic ischemia that occurred within 6 months of discontinuation of antiplatelet agents; the lesion was required to be correlated with the stented artery. RESULTS: The mean time of discontinuation of antiplatelet medication was 31.4 ± 18.3 months after SACE (median, 26 months). The majority of patients stopped antiplatelet medication between 18 and 36 months after SACE (74 patients, 61.6%). Laser-cut closed-cell stent was most commonly applied in 91 aneurysms (70.0%), followed by braided closed-cell (n=29; 22.3 %) and laser-cut open-cell stent 10 (7.7 %). No patients experienced cerebral ischemia related to discontinuation of antiplatelet medication. CONCLUSION: Our preliminary study suggests that it may be safe to discontinue antiplatelet medication after SACE in patients at low risk for ischemia. The optimal time to discontinue might be around 18 to 36 months after SACE. Large cohort-based studies or randomized clinical trials are warranted to confirm these results.

Endovascular treatment of medullary bridging vein-draining dural arteriovenous fistulas: foramen magnum vs. craniocervical junction lesions.

PURPOSE: Dural arteriovenous fistulas (AVFs) draining to medullary bridging vein (MBV) are located at foramen magnum (FM) and craniocervical junction (CCJ). Such fistulas are rare but pose a challenge to endovascular management. This study was undertaken to assess clinical manifestations, angiographic features, and outcomes of endovascular treatment in patients with MBV dural AVFs. METHODS: A number of our patients (N = 22) were diagnosed with MBV dural AVF and treated by endovascular means. There were 9 FM lesions and 13 CCJ lesions. We reviewed clinical records and imaging studies to define clinical characteristics, vascular anatomic details, and treatment outcomes, comparing FM- and CCJ-level subsets. RESULTS: Subjects ranged from 37 to 74 years of age (mean, 57.7 years) with male predominance (2.7:1). They presented with intracranial hemorrhage (11/22, 50%), myelopathy (8/22, 36%), or nonspecific symptoms (3/22, 14%). In 17 patients (77.3%), the shunts showed complete or near-complete occlusion following endovascular treatment (FM, 100%; CCJ, 61.5%). However, seven patients experienced ischemic events (FM, 11.1%; CCJ, 46.2%) and one patient sustained a hemorrhagic complication. No hemorrhages recurred during follow-up monitoring, and myelopathic symptoms abated. CONCLUSION: MBV dural AVFs are highly aggressive lesions for which proper diagnosis and treatment are of utmost importance. Although transarterial embolization proved highly successful in FM lesions, shunt occlusion was less frequent in the CCJ subset, with greater risk of ischemic complications.

Clinical Factors Associated with the Risk of Intracranial Aneurysm Rupture in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: The occurrence of intracranial aneurysms is higher in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the healthy population. However, research concerning the factors related to the risk of intracranial aneurysm rupture in patients with ADPKD is still insufficient. OBJECTIVES: The aim of the study was to investigate the prevalence of intracranial aneurysms and aneurysmal subarachnoid hemorrhage (SAH) and to analyze the systemic factors associated with high-risk aneurysms in patients with ADPKD. METHODS: We screened patients who underwent cerebral angiography between January 2007 and May 2017 in the ADPKD registry. Patients were examined for the presence of intracranial aneurysms and subsequently reclassified into 3 groups based on the risk of aneurysmal rupture: the aneurysm-negative (group 1), low-risk aneurysm (group 2), or high-risk aneurysm (group 3). Various systemic factors were compared, and independent factors associated with high-risk aneurysms were analyzed. RESULTS: Among the 926 patients, 148 (16.0%) had intracranial aneurysms and 11 (1.2%) had previous aneurysmal SAH. Patients with intracranial aneurysms were further classified into group 2 (low-risk aneurysms, 15.5%) or group 3 (high-risk aneurysms, 84.5%). Age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05, p = 0.004), female sex (OR 3.13, 95% CI 1.94-5.0 6, p < 0.001), dolichoectasia (OR 8.57, 95% CI 1.53-48.17, p = 0.015), and mitral inflow deceleration time (DT) (OR 1.01, 95% CI 1.00-1.01, p = 0.046) were independently associated with high-risk aneurysms, whereas hypercholesterolemia (OR 0.46, 95% CI 0.29-0.72, p = 0.001) was negatively associated. CONCLUSION: In the present study among patients with ADPKD, the prevalence of intracranial aneurysms and aneurysmal SAH was 16 and 1.2%, respectively. Age, female sex, dolichoectasia, and mitral inflow DT were positively associated with high-risk aneurysms, whereas hypercholesterolemia was negatively associated. A subsequent large-scaled longitudinal study is needed to define the plausibility of the clinical parameters.

Retrograde stenting through anterior communicating artery in coil embolization of the posterior communicating artery aneurysm: contralateral approach.

During coil embolization of wide-necked posterior communicating artery (PcomA) aneurysms, stent assistance is sometimes limited if PcomA is acutely angled at its origins from saccular neck. Herein, we present two instances where retrograde stenting was used for coil embolization of PcomA aneurysms. Both procedures involved a contralateral approach via anterior communicating artery (AcomA). To achieve this, the stent-delivery microcatheter was inserted retrograde from contralateral to ipsilateral internal carotid artery (ICA) across AcomA, arriving at ipsilateral PcomA. A separate microcatheter, passed through ipsilateral ICA, was then used to select the aneurysm sac for coil delivery. Coil embolization ultimately took place under protection of a horizontally placed stent extending from PcomA to terminal ICA. Each aneurysm was properly coiled and occluded, without procedural complications. This stenting technique is a reasonable option, offering a means of strategic coil embolization in wide-necked PcomA aneurysms and providing complete neck coverage through contralateral access.

Neurological Pupil Index as an Indicator of Neurological Worsening in Large Hemispheric Strokes.

BACKGROUND/OBJECTIVE: Cerebral herniation due to brain edema is the major cause of neurological worsening in patients suffering large hemispheric strokes. In this study, we investigated whether quantitative pupillary response could help identify the neurological worsening due to brain swelling in patients with large hemispheric strokes. METHODS: Quantitative pupillary assessment using an automated pupillometer (NPi-100) was performed between April 2017 and August 2019 for patients suffering large hemispheric strokes. Consecutive pupillary responses were measured every 2 or 4 h as a part of routine clinical care. We compared the mean neurological pupil index (NPi) values, NPi value at the time of neurological deterioration, and percentage change in NPi from the immediate previous value between patients with and without neurological worsening. RESULTS: In this study, 2442 quantitative pupillary assessments were performed (n = 30; mean age, 67.9 years; males, 60.0%). Among the included patients, 10 (33.3%) experienced neurological worsening. Patients with neurological worsening had a significantly lower mean value of NPi and a sudden decrease in the NPi value as compared to those without neurological worsening during the whole monitoring period (3.88 ± 0.65 vs. 4.45 ± 0.46, P < 0.001; and 29.5% vs. 11.1%, P = 0.006, respectively). All patients with NPi values below 2.8 showed neurological deterioration. CONCLUSIONS: Quantitative monitoring of the pupillary response using an automated pupillometer could be a useful and noninvasive tool for detecting neurological deterioration due to cerebral edema in large hemispheric stroke patients.

Endovascular management of multiple intracranial dural arteriovenous fistulas.

BACKGROUND AND PURPOSE: Multiply occurring intracranial dural arteriovenous fistulas (dAVFs) have been documented but rarely occur, and neither pathogenesis nor prognosis is clearly understood. This study was conducted to analyze angiographic characteristics of multiple dAVFs and to chronicle our treatment experience. METHODS: Between April, 2002 and January, 2018, data prospectively collected from 310 patients with intracranial dAVFs were systematically reviewed, assessing clinical and anatomic outcomes of endovascular treatment in 32 patients with multiple dAVFs (≥ 2 fistulas each). Lesions were categorized as multifocal or diffuse type, depending on presentation, and further characterized as progressive or non-progressive disease. RESULTS: Overall, 18 patients (56.3%) experienced aggressive presentations, including intracerebral hemorrhage or venous infarction. Cortical venous reflux (CVR) was observed in 26 patients (81.3%), and sinus thrombosis or occlusion was seen in 24 (75.0%). Clinical outcomes in patients with multifocal fistulas (n = 11) were excellent (100%), marked by a moderately high rate of complete occlusion (54.5%). Those with progressive disease (n = 10) regularly displayed certain angiographic findings, namely diffuse configuration (100%), sinus thrombosis (100%), and CVR (100%). Complete anatomic obliteration was achieved in 12 patients (37.5%), and in 26 patients (81.3%), clinical outcomes were favorable. CONCLUSION: Multiple dAVFs are typically aggressive at presentation, given strong associations with CVR and sinus thrombosis. In diffuse-type fistulas, the potential to recur or progress is high. Although definitive treatment poses a challenge, outcomes of endovascular therapeutics may be still optimized in this setting through strategic procedural modifications and careful follow-up monitoring.

Monitoring cerebral blood flow change through use of arterial spin labelling in acute ischaemic stroke patients after intra-arterial thrombectomy.

OBJECTIVES: To evaluate the ability of arterial spin labelling perfusion-weighted imaging (ASL-PWI) to identify reperfusion status and to predict the early neurological outcome of acute ischaemic stroke patients after intra-arterial (IA) thrombectomy. METHODS: A total of 51 acute ischaemic stroke patients who underwent IA thrombectomy were retrospectively reviewed. Asymmetrical index before and after IA thrombectomy (AICBFpre and AICBFpost) and volume ratio of the reperfused territory to the baseline perfusion abnormality (reperfusion volume ratio) were calculated on ASL-PWI. A paired t-test was used to compare AICBFpre and AICBFpost. Pearson correlation and multiple linear regression were performed to evaluate correlations between the imaging parameters and NIHSS scores. RESULTS: Mean AICBFpost was significantly higher than mean AICBFpre (0.923±0.352 vs. 0.312±0.191, p<0.001). AICBFpre had a significant correlation with NIHSSpre (pr=-0.430, p=.004). ∆AICBF had significant correlations with NIHSS24 h, NIHSS5-7 days and ∆NIHSS5-7 days (r=-0.356, p=0.028; r=-0.597, p<0.001; r=-0.346, p=0.033, respectively). ∆AICBF, reperfusion volume ratio and baseline infarct volume were significant independent predictors for NIHSS5-7 days. CONCLUSIONS: ASL-PWI has the potential to serve as a non-invasive imaging tool to monitor the reperfusion status and predict the early neurological outcome of acute ischaemic stroke patients after IA thrombectomy. KEY POINTS: • CBF change on ASL-PWI after IA thrombectomy correlated with NIHSS scores. • ASL-PWI can non-invasively monitor reperfusion in AIS patients after IA thrombectomy. • ASL-PWI may predict early outcome of AIS patients after IA thrombectomy.

Correction to: Does stent type impact coil embolization outcomes in extended follow-up of small-sized aneurysms (< 10 mm)?

The original version of this article contained a mistake in Fig. 4: Fig. 4a and d were interchanged. The correct figure is shown below. The original article has been corrected.

Does stent type impact coil embolization outcomes in extended follow-up of small-sized aneurysms (< 10 mm)?

PURPOSE: Self-expandable stents have enabled endovascular treatment of wide-necked aneurysms (ordinarily viewed as technically prohibitive), with favorable outcomes. However, the impact of stent type on occlusive stability has not been adequately investigated. In small-sized unruptured saccular aneurysms, we generated estimates of stent-assisted coil embolization outcomes during follow-up monitoring. Stent type and other risk factors linked to recanalization were analyzed. METHODS: A cohort of 286 patients harboring 312 small-sized unruptured aneurysms (< 10 mm) was subjected to mid-term and extended follow-up monitoring after stent-assisted coiling. Three types of stents (Enterprise, 192; Neuroform, 27; LVIS, 93) were deployed in this population; all medical records and radiologic data of which were reviewed. Mid-term recanalization rates and related risk factors were assessed using binary logistic regression analysis. RESULTS: A total of 49 aneurysms (15.7%) displayed recanalization at 6 months postembolization, with 34 and 15 instances of minor and major recanalization, respectively. Multivariate analysis indicated that wide-necked aneurysms (> 4 mm) (HR = 2.362; p = 0.017), incomplete occlusion at time of coiling (HR = 2.949; p = 0.002), and stent type (p = 0.048) were significant factors in mid-term recanalization, whereas hypertension (p = 0.095) and packing density ≤ 30% (p = 0.213) fell short of statistical significance. Compared with Enterprise (HR = 2.828) or Neuroform (HR = 4.206) stents, outcomes proved more favorable with use of LVIS. CONCLUSIONS: Above findings demonstrate that in addition to occlusive status at time of coil embolization and neck size, stent type may affect follow-up outcomes of stent-assisted coil embolization in small-sized aneurysms. LVIS (vs Enterprise or Neuroform stents) performed best during follow-up monitoring in terms of limiting recanalization.

Monitoring Cerebrovascular Reactivity through the Use of Arterial Spin Labeling in Patients with Moyamoya Disease.

PURPOSE: To assess arterial spin labeling in the identification of impaired cerebrovascular reactivity in patients with moyamoya disease. MATERIALS AND METHODS: The institutional review board approved this prospective study, and written informed consent was obtained from all patients. A prospective study was conducted in 78 subjects with moyamoya disease (of whom 31 underwent unilateral direct arterial anastomosis). The concordance between the cerebrovascular reactivity index values from arterial spin labeling and single photon emission computed tomography (SPECT) was assessed by using Bland-Altman analysis, and the area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of arterial spin labeling to depict impaired cerebrovascular reactivity (in which the cerebrovascular reactivity index value is less than 0% on SPECT images). RESULTS: The cerebrovascular reactivity index from arterial spin labeling had a lower value than that from SPECT (mean difference, -4.2%). The area under the receiver operating characteristic curve for arterial spin labeling in the detection of impaired cerebrovascular reactivity was at least 0.85. On the anastomotic side, a significant increase was found between the cerebrovascular reactivity index values on arterial spin labeling images obtained preoperatively and those obtained 6 months after surgery, as well as on SPECT images (mean ± standard deviation values of cerebrovascular reactivity index increased by 5.9% ± 10.9 and 3.0% ± 6.3 for arterial spin labeling and SPECT, respectively). CONCLUSION: Arterial spin labeling has excellent performance in the identification of impaired cerebrovascular reactivity in patients with moyamoya disease, and it has the potential to serve as a noninvasive imaging tool to monitor cerebrovascular reactivity in patients with moyamoya disease.

Extended monitoring of coiled aneurysms completely occluded at 6-month follow-up: late recanalization rate and related risk factors.

OBJECTIVES: To estimate long-term durability in coiled aneurysms completely occluded at 6-month follow-up imaging, focusing on late recanalization rate and the risk factors involved. METHODS: A cohort of 620 patients harbouring 698 completely occluded coiled aneurysms at 6-month follow-up was subjected to extended monitoring (mean, 24.5 ± 7.9 months). Cumulative recanalization rate and related risk factors were analysed using Cox proportional hazards regression and Kaplan-Meier product-limit estimator. RESULTS: Forty-three aneurysms (6.2 %) occluded completely at 6-months displayed recanalization (3.02 % per aneurysm-year) during continued surveillance (1425.5 aneurysm-years), with 26 (60.5 %) surfacing in another 6 months, 15 (34.9 %) within 18 months and 2 (4.6 %) within 30 months. Cumulative survival rates without recanalization were significantly lower in subjects with aneurysms >7 mm (p = 0.014), with bifurcation aneurysms (p = 0.009) and with subarachnoid haemorrhage (SAH) at presentation (p < 0.001). Multivariate analysis indicated that aneurysms >7 mm (HR = 2.37, p = 0.02) and bifurcation aneurysms (HR = 2.70, p = 0.03) were significant factors in late recanalization, whereas a link with SAH at presentation was marginal (HR = 1.92, p = 0.06) and stent placement fell short of statistical significance (HR = 0.47; p = 0.12). CONCLUSION: Most (93.8 %) coiled aneurysms showing complete occlusion at 6 months post-procedure were stable in long-term monitoring. However, aneurysms >7 mm and bifurcation aneurysms were predisposed to late recanalization. KEY POINTS: • Most coiled aneurysms showing complete occlusion at 6 months were stable. • Forty-three aneurysms (6.2 %) occluded completely at 6-month follow-up displayed late recanalization. • Late recanalization rate was 3.02 % per aneurysm-year during follow-up of 1425.5 aneurysm-years. • Aneurysms over 7 mm and bifurcation aneurysms were predisposed to late recanalization.

Deregulation of Retinaldehyde Dehydrogenase 2 Leads to Defective Angiogenic Function of Endothelial Colony-Forming Cells in Pediatric Moyamoya Disease.

OBJECTIVE--: Moyamoya disease (MMD) is a common cause of childhood stroke, in which the abnormal function of the endothelial colony-forming cell (ECFC) plays a key role in the pathogenesis of the disease. This study was designed to identify genes involved in MMD pathogenesis using gene expression profiling and to understand the defective function of MMD ECFCs. APPROACH AND RESULTS--: We compared gene expression profiles of ECFCs isolated from patients with MMD and normal controls. Among the differentially expressed genes, we selected a gene with the most downregulated expression, retinaldehyde dehydrogenase 2 (RALDH2). The activity of RALDH2 in MMD ECFCs was assessed by in vitro tube formation assay and in vivo Matrigel plug assay in the presence of all-trans retinoic acid. The transcriptional control of RALDH2 was tested using ChIP assays on acetyl-histone H3. In the results, MMD ECFCs inefficiently formed capillary tubes in vitro and capillaries in vivo, a defect restored by all-trans retinoic acid treatment. Knockdown of RALDH2 mRNA in normal ECFCs also induced decreased activity of capillary formation in vitro. The decreased level of RALDH2 mRNA in MMD ECFCs was attributed to defective acetyl-histone H3 binding to the promoter region. CONCLUSIONS--: From these results, we conclude that the expression of RALDH2 was epigenetically suppressed in ECFCs from patients with MMD, which may play a key role in their functional impairment.

Pediatric spinal arteriovenous malformations and fistulas: a single institute's experience.

OBJECTIVE: Pediatric spinal vascular diseases are extremely rare. We aimed to evaluate their clinical characteristics and treatment outcomes in our institute. DESIGN: A total of 10 patient files were retrospectively reviewed, including 3 cases of intramedullary arteriovenous malformations (AVMs), 6 cases of perimedullary arteriovenous fistulas (AVFs), and 1 case of epidural AVF. Clinical features, radiological findings, treatment results, and clinical outcomes were evaluated. The median durations of the radiologic and clinical follow-ups were 17.7 and 107.9 months, respectively. RESULTS: The male to female ratio was 1:1, with a median age at diagnosis of 9 years. All AVMs were juvenile type, all perimedullary AVFs were high flow types (three type IVb and three type IVc), and one epidural AVF was associated with intradural venous drainage. Most cases (90 %) were located in the cervical spine and conus medullaris. Acute neurological deterioration was identified in five patients; however, bleeding was identified in only one patient. Two cases were surgically treated, seven cases underwent embolization, and one case underwent radiosurgery. Three cases were completely obliterated, and their clinical states were improved (n = 2; 66.7 %) and stationary (n = 1; 33.3 %). Meanwhile, seven cases were incompletely obliterated, and their clinical states were improved (n = 2; 28.6 %), stationary (n = 3; 42.8 %), and aggravated (n = 2; 28.6 %). CONCLUSIONS: Pediatric spinal AVMs and AVFs were mostly complex and high flow types, and complete obliteration could not be satisfactorily achieved. Incompletely treated lesions should be closely followed up because they may worsen.