Multiplexed Quantitative Proteomics Reveals Proteomic Alterations in Two Rodent Traumatic Brain Injury Models.

In many cases of traumatic brain injury (TBI), conspicuous abnormalities, such as scalp wounds and intracranial hemorrhages, abate over time. However, many unnoticeable symptoms, including cognitive, emotional, and behavioral dysfunction, often last from several weeks to years after trauma, even for mild injuries. Moreover, the cause of such persistence of symptoms has not been examined extensively. Recent studies have implicated the dysregulation of the molecular system in the injured brain, necessitating an in-depth analysis of the proteome and signaling pathways that mediate the consequences of TBI. Thus, in this study, the brain proteomes of two TBI models were examined by quantitative proteomics during the recovery period to determine the molecular mechanisms of TBI. Our results show that the proteomes in both TBI models undergo distinct changes. A bioinformatics analysis demonstrated robust activation and inhibition of signaling pathways and core proteins that mediate biological processes after brain injury. These findings can help determine the molecular mechanisms that underlie the persistent effects of TBI and identify novel targets for drug interventions.

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.

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.

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.

Revascularization Evaluation in Adult-Onset Moyamoya Disease after Bypass Surgery: Superselective Arterial Spin Labeling Perfusion MRI Compared with Digital Subtraction Angiography.

Background A superselective (SS) arterial spin labeling (ASL) MRI technique can be used to monitor the revascularization area as a supplementary or alternative modality to digital subtraction angiography (DSA), with the advantage of being noninvasive. Purpose To evaluate whether SS-ASL perfusion MRI could be used to visualize the revascularization area after combined direct and indirect bypass surgery in adults with moyamoya disease compared with DSA. Materials and Methods Patients diagnosed with moyamoya disease who underwent DSA and SS-ASL 6 months after surgery between June 2017 and November 2019 in a single institution were retrospectively evaluated. Subjective grading of the revascularization area and collateral grading in 10 Alberta Stroke Program Early CT Score (ASPECTS) locations were performed. The change in perfusion status in a subgroup that underwent both preoperative and postoperative SS-ASL studies was evaluated. Intermodality agreement was analyzed by using weighted κ statistics. Results Thirty-seven hemispheres from 33 patients (mean age, 39 years ± 12 [standard deviation]; 20 women) were evaluated. The intermodality agreement of the revascularization area grading was substantial (weighted κ = 0.70; 95% confidence interval [CI]: 0.37, 1.00). The overall intermodality agreement of the postoperative collateral grading in the 10 ASPECTS locations for all vessels was substantial (weighted κ = 0.77; 95% CI: 0.74, 0.80). For the presence of postoperative collateral supplied by the ipsilateral external carotid artery in 10 ASPECTS locations (a total of 370 locations) using DSA as a reference test, the SS-ASL showed a sensitivity of 92% (183 of 199 locations; 95% CI: 87%, 95%) and a specificity of 83% (142 of 171 locations; 95% CI: 77%, 88%). The overall intermodality agreement of the changes in perfusion status was moderate (weighted κ = 0.59; 95% CI: 0.54, 0.65). Conclusion Superselective arterial spin labeling imaging precisely depicted the revascularization territory in patients with moyamoya disease who underwent bypass surgery, and it showed the changes in the vascular supplying territories before and after bypass surgery. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Hendrikse in this issue.

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.

Ivy Sign Predicts Ischemic Stroke Recurrence in Adult Moyamoya Patients without Revascularization Surgery.

BACKGROUND: Although there is a standard guideline for performing revascularization surgery in patients with Moyamoya diseases (MMD), more objective and easily obtainable predictors are still needed. OBJECTIVES: In this study, we aimed to evaluate the relationship between an ipsilateral ivy sign and ischemic stroke recurrence in adult MMD patients without revascularization surgery. METHODS: We included consecutive MMD patients without revascularization surgery between 2006 and 2014. The ivy sign was defined as a linear or focal high-signal intensity on fluid-attenuated inversion recovery images, and the burdens of ivy sign were rated in each hemisphere. The ischemic stroke recurrence was defined as a new clinical event that accompanied a new brain lesion on magnetic resonance imaging. RESULTS: Overall, 84 patients with 154 hemispheres were analyzed. We found recurrent ischemic stroke in 9 (6%) hemispheres within 3 years. In multivariate analysis, an ipsilateral ivy sign remained an independent predictor of 3-year ischemic recurrence (adjusted hazard ratio [aHR] 10.15, 95% CI 2.10-49.14, p = 0.004). An initial presentation as infarction was also significant (aHR 7.15, 95% CI 1.36-36.78, p = 0.019). The burdens of ivy sign showed a dose-response tendency with the 3-year ischemic recurrence rate (p < 0.001). When comparing the ischemic recurrence rate among 4 groups with and without ivy sign and perfusion defect, the "Ivy sign (+) Perfusion defect (+) group" showed a significantly higher risk in both observed (p = 0.005) and estimated (p = 0.003) 3-year ischemic recurrence than did the other group. Additionally, the "Ivy sign (+) Perfusion defect (-) group" showed a higher recurrence rate than did the "Ivy sign (-) Perfusion defect (+) group". CONCLUSIONS: The ivy sign is associated with ischemic recurrence in adult MMD patients in a dose-response manner. It would be helpful for selecting high-risk patients who need revascularization surgery.

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.

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.

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.

750 GeV Diphoton Excess May Not Imply a 750 GeV Resonance.

We discuss nonstandard interpretations of the 750 GeV diphoton excess recently reported by the ATLAS and CMS Collaborations which do not involve a new, relatively broad resonance with a mass near 750 GeV. Instead, we consider the sequential cascade decay of a much heavier, possibly quite narrow, resonance into two photons along with one or more additional particles. The resulting diphoton invariant mass signal is generically rather broad, as suggested by the data. We examine three specific event topologies-the "antler," the "sandwich," and the two-step cascade decay-and show that they all can provide a good fit to the observed published data. In each case, we delineate the preferred mass parameter space selected by the best fit. In spite of the presence of extra particles in the final state, the measured diphoton p_{T} spectrum is moderate due to its anticorrelation with the diphoton invariant mass. We comment on the future prospects of discriminating with higher statistics between our scenarios, as well as from more conventional interpretations.

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.

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.

Modified coil protection for proper coil frame configuration in wide-necked aneurysms.

INTRODUCTION: Although various protective techniques for treating wide-necked intracranial aneurysms currently exist and continue to evolve, their utility may be limited in some lesions with complex configurations, small-caliber channels, or inherently tortuous vascular patterns. Described herein is a modified coil protection technique as a novel adjunct for proper coil frame configuration. METHODS: Initially, a microcatheter is passed into aneurysmal sac, and the first coil is inserted to build a frame. Inevitably, some coils may abut opposite poles of aneurysms and protrude into parent arteries. Should this happen, a second microcatheter may be placed at the site of coil protrusion, so that a separate and smaller coil may be partially deployed for protection. A framing coil may then be configured within aneurysmal sac, under protection of the secondary coil. Once the first coil is entirely in place, the remainder of second coil is carefully inserted, and additional coil may be inserted as needed via dual microcatheters. RESULTS: This technique was successfully applied to 23 saccular intracranial aneurysms of internal carotid (n = 8), middle cerebral (n = 6), anterior cerebral (n = 6), and superior cerebellar artery (n = 3), combining stent protection in two patients and balloon remodeling in one. Selective endovascular treatment was effective as a result. Excellent outcomes were achieved in all patients, with no morbidity or mortality directly related to the modified procedure. CONCLUSION: As suggested by outcomes of this small study, our modified coil protection method may be a safe option if traditional coiling strategies are not feasible, enabling stable coil frame configuration in wide-necked aneurysms.

Progressive thrombosis of small saccular aneurysms filled with contrast immediately after coil embolization: analysis of related factors and long-term follow-up.

INTRODUCTION: Although it is well-known that incomplete occlusion of aneurysms after coil embolization predisposes to later recanalization, not all aneurysms will be fully occluded by coiling. In follow-up, we evaluated outcomes of small aneurysms (<10 mm) that showed filling of the sac with contrast immediately after coil embolization and assessed factors implicated in subsequent progressive thrombosis. METHODS: Between January 2008 and December 2010, a total of 1035 aneurysms in 898 patients were treated by endovascular coiling. Of these, 210 small aneurysms displayed filling of the sac by contrast immediately after coil embolization. Time-of-flight magnetic resonance angiography (TOF-MRA; at 6, 12, 24, and 36 months) and digital subtraction angiography (as needed) were used for postoperative monitoring. Complete occlusion of these aneurysms at the 6-month follow-up point was attributed to progressive thrombosis. RESULTS: In 186 (88.5 %) of the 210 aneurysms that showed filling of the sac with contrast, complete occlusion was observed on follow-up imaging studies at 6 months. Multiple logistic regression analysis indicated that progressive thrombosis was linked to aneurysmal neck diameter ≤4 mm (p < 0.001) and packing density >30 % (p = 0.016). Aneurysms originating from non-branching vessels were of marginal statistical significance (p = 0.056). In 179 progressively thrombosed aneurysms with follow-up evaluations of ≥12 months (mean, 31.9 ± 7.6 months), 168 aneurysms (93.9 %) exhibited stable occlusion, whereas minor recanalization was observed in 6 (3.3 %) instances, and major recanalization occurred in 5 (2.8 %). CONCLUSIONS: In aneurysms where filling of the sac with contrast was demonstrable after coil embolization, aneurysms with small neck diameters or high coil packing density, and non-branching aneurysms seem predisposed to progressive intra-aneurysmal thrombosis over the course of time.

Morphology and related hemodynamics of the internal carotid arteries of moyamoya patients.

BACKGROUND: Morphological studies investigating the intracranial-extradural internal carotid artery with moyamoya disease have not been reported. We designed this case-control study to investigate the morphological differences of the internal carotid artery with moyamoya disease, and to clarify the contributions of these differences to the resultant fluid dynamics. METHODS: Patients with moyamoya disease and normal controls were assigned to each group. The vascular tortuosity of internal carotid artery was measured with three-dimensional rendering using magnetic resonance angiography. By computational fluid dynamics, hemodynamic characteristics were simulated and compared between two groups. RESULTS: Distances were measured from the carotid canal to the siphon. A shorter actual distance was observed in the moyamoya group (p = 0.0170). Vascular tortuosity was significantly low in moyamoya patients showing lower curvature angles in the petrous and intra-cavernous segments (p = 0.0012). Less blood flowed (p < 0.0001) through the narrower internal carotid artery (p < 0.0001) in the moyamoya group at the carotid canal level. The blood flow velocities were not significantly different (p = 0.2332). Faster blood flow and higher wall shear stress in the internal carotid artery bifurcation were verified with computational fluid dynamics. CONCLUSIONS: Significant morphological differences were confirmed to exist in the intracranial-extradural internal carotid artery of moyamoya patients. These differences might influence the hemodynamics around the bifurcation of the internal carotid artery.

Long-term outcomes after combined revascularization surgery in adult moyamoya disease.

BACKGROUND AND PURPOSE: The surgical outcomes of adult moyamoya disease are rarely reported. We aimed to evaluate the long-term outcomes of combined revascularization surgery in patients with adult moyamoya disease. METHODS: Combined revascularization surgery consisting of superficial temporal artery-middle cerebral artery anastomosis with encephalodurogaleosynangiosis was performed on 77 hemispheres in 60 patients. Clinical, angiographic, and hemodynamic states were evaluated retrospectively using quantitative methods preoperatively and postoperatively in the short-term (≈6 months) and long-term (≈5 years) periods. The mean clinical follow-up duration was 71.0±10.1 months (range, 60-104 months). RESULTS: Clinical status improved until 6 months after surgery and remained stable thereafter, as assessed by the Karnofsky Performance Scale and modified Rankin Scale. The revascularization area relative to supratentorial area significantly increased in the long-term period compared with that in the short-term period (54.8% versus 44.2%; P<0.001). Cerebral blood flow in the territory of the middle cerebral artery improved in the short-term period compared with that in the preoperative period (68.7 versus 59.1; considering blood flow of the pons as 50; P<0.001) and thereafter became stable (65.5 in the long term; P=0.219). The annual risks of symptomatic hemorrhage and infarction were 0.4% and 0.2%, respectively, in the operated hemispheres. CONCLUSIONS: Combined revascularization surgery resulted in satisfactory long-term improvement in clinical, angiographic, and hemodynamic states and prevention of recurrent stroke.