Glocal is a linguistic hybrid of global and local. This paper discusses neuroendovascular therapy and stroke treatment by comparing the differences in the world, Japan, and the Ibaraki Prefecture, ...where the University of Tsukuba is located. Neuroendovascular therapy was developed by neuroradiologists in Europe and the United States using newly developed devices, which expanded its indications. It plays an important role in the surgical treatment of stroke. In Japan, neurosurgeons are mainly in-charge. The previous device lag has improved. Due to the wide availability of doctors in-charge and the associated facilities, the experience of each doctor is limited. In Japan, board-certified neuroendovascular therapy specialists are trained via a rigorous curriculum and examination process. This strict curriculum ensures that doctors maintain their knowledge and skills. The Ibaraki Prefecture has a serious shortage of doctors and a high stroke mortality rate. Hence, we are addressing this problem through cooperation with stroke centers using information and communication technology and using educational activities for elementary school students.
The medical treatment for stroke has advanced greatly in recent years. Thrombolytic therapy with tissue plasminogen activator (t-PA) is one of the mainstream treatments, but it still has many ...problems, including short half-life, and t-PA-induced reperfusion and oxidative injuries. To broaden the therapeutic window of t-PA and reduce its associated oxidative stress after reperfusion, t-PA-installed, nitroxide radical-containing, self-assembled polyion complex nanoparticles (t-PA@iRNP) were designed. Encapsulation of t-PA in the self-assembled antioxidant nanoparticles improved its bioavailability and extended its therapeutic window. To suppress reactive oxygen species (ROS) in the ischemic penumbra area, the low-molecular-weight nitroxide antioxidant 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl was covalently conjugated with the nanoparticle matrix, thus suppressing oxidative damage in the brain after reperfusion. t-PA and nitroxide radicals were confined and protected in the core of t-PA@iRNP, thereby preventing their rapid metabolism and excretion out of the body after systemic circulation for prolonged period. The nano-sized formulation prevented non-specific internalization of t-PA@iRNP in healthy cells, thereby preserving the normal function of redox reactions in the cells, especially important redox reactions such as electron transport chains. This improved pharmacological performance of t-PA@iRNP remarkably extended the in vivo half-life of t-PA in systemic circulation. Using a mouse model of photo-thrombotic middle cerebral artery occlusion, we found that t-PA@iRNP treatment, compared with naked t-PA, void iRNP, or t-PA@niRNP (non-ROS scavenging nanoparticle as a control), significantly suppressed increases in cerebral infarct volume and improved neurological deficit after brain ischemia. t-PA-induced subarachnoid hemorrhage was also suppressed by t-PA@iRNP treatment through elimination of overproduced ROS. Based on these data, t-PA@iRNP presents therapeutic potential through synergistic effect of thrombolysis and antioxidant effects for preventing and treating ischemia-reperfusion injury.
The number of patients with traumatic intracranial hemorrhage (tICH) that are taking antithrombotics (ATs), antiplatelets (APs) and/or anticoagulants (ACs), has increased, but the influence of it for ...outcome remains unclear. This study aimed to evaluate an influence of AT for tICH. We retrospectively reviewed all patients with tICH treated between 2012 and 2019, and analyzed demographics, neurological status, clinical course, radiological findings, and outcome data. A total of 393 patients with tICH were included; 117 were on AT therapy (group A) and 276 were not (group B). Fifty-one (43.6%) and 159 (57.6%) patients in groups A and B, respectively, exhibited mRS of 0-2 at discharge (p = 0.0113). Mortality at 30 days was significantly higher in group A than in group B (25.6% vs 16.3%, p = 0.0356). Multivariate analysis revealed that higher age (OR 32.7, p < 0.0001), female gender (OR 0.56, p = 0.0285), pre-injury vitamin K antagonist (VKA; OR 0.42, p = 0.0297), and hematoma enlargement (OR 0.27, p < 0.0001) were associated with unfavorable outcome. AP and direct oral anticoagulant were not. Hematoma enlargement was significantly higher in AC-users than in non-users. Pre-injury VKA was at high risk of poor prognosis for patients with tICH. To improve outcomes, the management of VKA seems to be important.
OBJECTIVE The aim of this retrospective multicenter cohort study was to assess the details of the angioarchitecture of arteriovenous fistulas (AVFs) at the craniocervical junction (CCJ) and to ...determine the associations between the angiographic characteristics and the clinical presentations and outcomes. METHODS The authors analyzed angiographic and clinical data for patients with CCJ AVFs from 20 participating centers that are members of the Japanese Society for Neuroendovascular Therapy (JSNET). Angiographic findings (feeding artery, location of AV shunt, draining vein) and patient data (age, sex, presentation, treatment modality, outcome) were tabulated and stratified based on the angiographic types of the lesions, as diagnosed by a member of the CCJ AVF study group, which consisted of a panel of 6 neurointerventionalists and 1 spine neurosurgeon. RESULTS The study included 54 patients (median age 65 years, interquartile range 61-75 years) with a total of 59 lesions. Five angiographic types were found among the 59 lesions: Type 1, dural AVF (22 37% of 59); Type 2, radicular AVF (17 29% of 59); Type 3, epidural AVF (EDAVF) with pial feeders (8 14% of 59); Type 4, EDAVF (6 10% of 59); and Type 5, perimedullary AVF (6 10% of 59). In almost all lesions (98%), AV shunts were fed by radiculomeningeal arteries from the vertebral artery that drained into intradural or epidural veins through AV shunts on the dura mater, on the spinal nerves, in the epidural space, or on the spinal cord. In more than half of the lesions (63%), the AV shunts were also fed by a spinal pial artery from the anterior spinal artery (ASA) and/or the lateral spinal artery. The data also showed that the angiographic characteristics associated with hemorrhagic presentations-the most common presentation of the lesions (73%)-were the inclusion of the ASA as a feeder, the presence of aneurysmal dilatation on the feeder, and CCJ AVF Type 2 (radicular AVF). Treatment outcomes differed among the angiographic types of the lesions. CONCLUSIONS Craniocervical junction AVFs commonly present with hemorrhage and are frequently fed by both radiculomeningeal and spinal pial arteries. The AV shunt develops along the C-1 or C-2 nerve roots and can be located on the spinal cord, on the spinal nerves, and/or on the inner or outer surface of the dura mater.
The purpose of this study is to compare the angiographic and clinical characteristics of spinal epidural arteriovenous fistulas (SEAVFs) and spinal dural arteriovenous fistulas (SDAVFs) of the ...thoracolumbar spine.
A total of 168 cases diagnosed as spinal dural or extradural arteriovenous fistulas of the thoracolumbar spine were collected from 31 centers. Angiography and clinical findings, including symptoms, sex, and history of spinal surgery/trauma, were retrospectively reviewed. Angiographic images were evaluated, with a special interest in spinal levels, feeders, shunt points, a shunted epidural pouch and its location, and drainage pattern, by 6 readers to reach a consensus.
The consensus diagnoses by the 6 readers were SDAVFs in 108 cases, SEAVFs in 59 cases, and paravertebral arteriovenous fistulas in 1 case. Twenty-nine of 59 cases (49%) of SEAVFs were incorrectly diagnosed as SDAVFs at the individual centers. The thoracic spine was involved in SDAVFs (87%) more often than SEAVFs (17%). Both types of arteriovenous fistulas were predominant in men (82% and 73%) and frequently showed progressive myelopathy (97% and 92%). A history of spinal injury/surgery was more frequently found in SEAVFs (36%) than in SDAVFs (12%;
=0.001). The shunt points of SDAVFs were medial to the medial interpedicle line in 77%, suggesting that SDAVFs commonly shunt to the bridging vein. All SEAVFs formed an epidural shunted pouch, which was frequently located in the ventral epidural space (88%) and drained into the perimedullary vein (75%), the paravertebral veins (10%), or both (15%).
SDAVFs and SEAVFs showed similar symptoms and male predominance. SDAVFs frequently involve the thoracic spine and shunt into the bridging vein. SEAVFs frequently involve the lumbar spine and form a shunted pouch in the ventral epidural space draining into the perimedullary vein.
Aim: To examine the efficacy and safety of prasugrel vs clopidogrel in thrombotic stroke patients at risk of ischemic stroke.Methods: This multicenter, active-controlled, randomized, double-blind, ...double-dummy, parallel group study enrolled thrombotic stroke patients aged ≥ 50 years at risk of ischemic stroke. Patients received prasugrel (3.75 mg/day) or clopidogrel (75 or 50 mg/day) for 24–48 weeks; other antiplatelet drugs were prohibited. The primary efficacy endpoint was the composite incidence of ischemic stroke, myocardial infarction (MI), and death from other vascular causes from the start to 1 day after treatment completion or discontinuation. Secondary efficacy endpoints included the incidences of ischemic stroke, MI, death from other vascular causes, ischemic stroke and transient ischemic attack, and stroke. Safety endpoints included bleeding events and adverse events (AEs).Results: In the prasugrel (N=118) and clopidogrel (N=112; all received 75 mg) groups, the primary efficacy endpoint composite incidence (95% confidence interval) was 6.8% (3.0%–12.9%) and 7.1% (3.1%–13.6%), respectively. The risk ratio (prasugrel/clopidogrel) was 0.949 (0.369–2.443). Secondary efficacy endpoints followed a similar trend. The combined incidences of life-threatening, major, and clinically relevant bleeding were 5.0% and 3.5% in the prasugrel and clopidogrel groups, respectively. The incidences of all bleeding events and AEs were 19.2% and 24.6% and 76.7% and 82.5% in the prasugrel and clopidogrel groups, respectively. No serious AEs were causally related to prasugrel.Conclusions: We observed a risk reduction of 5% with prasugrel vs clopidogrel, indicating comparable efficacy. There were no major safety issues for prasugrel.
Abstract
BACKGROUND
Flow diverters (FDs) have marked the beginning of innovations in the endovascular treatment of large unruptured intracranial aneurysms, but no multi-institutional studies have ...been conducted on these devices from both the clinical and economic perspectives.
OBJECTIVE
To compare retreatment rates and healthcare expenditures between FDs and conventional coiling-based treatments in all eligible cases in Japan.
METHODS
We identified patients who had undergone endovascular treatments during the study period (October 2015-March 2018) from a national-level claims database. The outcome measures were retreatment rates and 1-yr total healthcare expenditures, which were compared among patients who had undergone FD, coiling, and stent-assisted coiling (SAC) treatments. The coiling and SAC groups were further categorized according to the number of coils used. Retreatment rates were analyzed using Cox proportional hazards models, and total expenditures were analyzed using multilevel mixed-effects generalized linear models.
RESULTS
The study sample comprised 512 FD patients, 1499 coiling patients, and 711 SAC patients. The coiling groups with ≥10 coils and ≥9 coils had significantly higher retreatment rates than the FD group with hazard ratios of 2.75 (1.30-5.82) and 2.52 (1.24-5.09), respectively. In addition, the coiling group with ≥10 coils and SAC group with ≥10 coils had significantly higher 1-year expenditures than the FD group with cost ratios (95% CI) of 1.30 (1.13-1.49) and 1.31 (1.15-1.50), respectively.
CONCLUSION
In this national-level study, FDs demonstrated significantly lower retreatment rates and total expenditures than conventional coiling with ≥ 9 coils.
Background and Purpose
Endovascular trapping of the vertebral artery dissecting aneurysms (VADAs) carries a risk of medullary infarction due to the occlusion of the perforating arteries. We evaluated ...the detectability and anatomical variations of perforating arteries arising from the vertebral artery (VA) using three-dimensional DSA.
Methods
In 120 patients without VA lesions who underwent rotational vertebral arteriography, the anatomical configurations of perforating arteries from the VA were retrospectively evaluated on the bi-plane DSA and reconstructed images to reach the consensus between two experienced reviewers. The images were interpreted by focusing on the numbers and types of perforating arteries, the relationships between the number of perforators and the anatomy of the VA and its branches.
Results
Zero, 1, 2, 3, 4, and 6 perforators were detected in 2, 51, 56, 9, 1, and 1 patient, respectively (median of 2 perforators per VA). The 200 perforators were classified into 146 terminal and 54 longitudinal course types and into 32 ventral, 151 lateral, and 17 dorsolateral distribution types. All ventral type perforators were also terminal type. In contrast, the longitudinal type was seen in 28.5% of lateral types and in 65% of dorsolateral types. Regarding the difference in the origin of the posterior inferior cerebellar artery (PICA), non-PICA type VAs gave off larger number of perforators than the other types of VAs.
Conclusions
Non-PICA type VAs give off a significantly larger number of perforators than other types, indicating that the trapping of non-PICA type VAs is associated with a risk of ischemic complications.
Immediate postcraniotomy headache frequently occurs within the first 48 h after surgery. The mechanisms underlying immediate postcraniotomy headache are not yet fully understood, and effective ...treatments are not yet established. This study aimed to identify the factors associated with immediate postcraniotomy headache in patients who underwent clipping surgery with frontotemporal craniotomy and to examine the effects of these factors on postcraniotomy headache. A total of 51 patients were included in this study. Immediate postcraniotomy headache was defined as pain with numerical rating scale score ≥4 on postoperative day 7. Sixteen patients (31.4%) had immediate postcraniotomy headache. The headache-positive group had a higher incidence of preoperative analgesic use (50.0% vs. 5.7%, respectively, p < 0.001), increased temporal muscle swelling ratio (137.0%±30.2% vs. 112.5%±30.5%, respectively, p = 0.01), and higher postoperative analgesic use (12.9±5.8 vs. 6.7±5.2, respectively, p < 0.001) than the headache-negative group. The risk factors independently associated with immediate postcraniotomy headache were preoperative analgesic use and temporal muscle swelling by >115.15% compared with the contralateral side in the receiver operating characteristic analysis. Postcraniotomy headache was significantly more common in patients with preoperative analgesic use and temporal muscle swelling than in those without (p < 0.001 and p = 0.002, respectively). Altogether, patients with immediate postcraniotomy headache had greater preoperative analgesic use, greater temporal muscle swelling ratio, and higher postoperative analgesic use than those without. Thus, temporal muscle swelling is a key response to immediate postcraniotomy headache.
OBJECTIVE The importance of a framing coil (FC)-the first coil inserted into an aneurysm during endovascular coiling, also called a lead coil or a first coil-is recognized, but its impact on ...long-term outcomes, including recanalization and retreatment, is not well established. The purposes of this study were to test the hypothesis that the FC is a significant factor for aneurysmal recurrence and to provide some insights on appropriate FC selection. METHODS The authors retrospectively reviewed endovascular coiling for 280 unruptured intracranial aneurysms and gathered data on age, sex, aneurysm location, aneurysm morphology, maximal size, neck width, adjunctive techniques, recanalization, retreatment, follow-up periods, total volume packing density (VPD), volume packing density of the FC, and framing coil percentage (FCP; the percentage of FC volume in total coil volume) to clarify the associated factors for aneurysmal recurrence. RESULTS Of 236 aneurysms included in this study, 33 (14.0%) had recanalization, and 18 (7.6%) needed retreatment during a mean follow-up period of 37.7 ± 16.1 months. In multivariate analysis, aneurysm size (odds ratio OR = 1.29, p < 0.001), FCP < 32% (OR 3.54, p = 0.009), and VPD < 25% (OR 2.96, p = 0.015) were significantly associated with recanalization, while aneurysm size (OR 1.25, p < 0.001) and FCP < 32% (OR 6.91, p = 0.017) were significant predictors of retreatment. VPD as a continuous value or VPD with any cutoff value could not predict retreatment with statistical significance in multivariate analysis. CONCLUSIONS FCP, which is equal to the FC volume as a percentage of the total coil volume and is unaffected by the morphology of the aneurysm or the measurement error in aneurysm length, width, or height, is a novel predictor of recanalization and retreatment and is more significantly predictive of retreatment than VPD. To select FCs large enough to meet the condition of FCP ≥ 32% is a potential relevant factor for better long-term outcomes. These findings support our hypothesis that the FC is a significant factor for aneurysmal recurrence.
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