Development of extended pharmacokinetic models for propofol based on measured blood and brain concentrations.

Propofol's pharmacokinetics have been extensively studied using human blood samples and applied to target-controlled infusion systems; however, information on its concentration in the brain remains scarce. Therefore, this study aimed to simultaneously measure propofol plasma and brain concentrations in patients who underwent awake craniotomy and establish new pharmacokinetic model. Fifty-seven patients with brain tumors or brain lesions who underwent awake craniotomy were sequentially assigned to model-building and validating groups. Plasma and brain (lobectomy or uncapping margins) samples were collected at five time-points. The concentration of propofol was measured using high-performance liquid chromatography. Population pharmacokinetic analysis was conducted through a nonlinear mixed-effects modeling program using a first-order conditional estimation method with interactions. Propofol's brain concentrations were higher than its plasma concentrations. The measured brain concentrations were higher than the effect site concentrations using the previous models. Extended models were constructed based on measured concentrations by incorporating the brain/plasma partition coefficient (Kp value). Extended models showed good predictive accuracy for brain concentrations in the validating group. The Kp value functioned as a factor explaining retention in the brain. Our new pharmacokinetic models and Kp value can predict propofol's brain and plasma concentrations, contributing to safer and more stable anesthesia.

Impact of collagen matrix on reconstructive material selection and postoperative complications in endoscopic endonasal skull base surgery.

OBJECTIVE: The aim of this study was to investigate the impact of collagen matrix on reconstructive material selection and postoperative complications in endoscopic endonasal skull base surgery. METHODS: The authors retrospectively reviewed the data of consecutive patients who underwent purely endoscopic endonasal skull base surgery from January 2015 to March 2023. Intraoperative CSF leakage was classified according to the Esposito grade, and skull base repair was tailored to the leakage grade. The patients were divided into two groups: before (group A) and after (group B) collagen matrix implementation. The rates of autologous graft harvesting (fat, fascia, and nasoseptal flap), postoperative CSF leakage, and donor-site complications were compared between the two groups. RESULTS: In total, 270 patients were included. Group A included 159 patients and group B included 111 patients. There were no differences in patient characteristics, including age, pathology, and Esposito grade, between the two groups. The overall fat usage rate was significantly higher in group A (63.5%) than in group B (39.6%) (p = 0.0001), and the fascia usage rate was also significantly higher in group A (25.8%) than in group B (4.5%) (p < 0.0001). The nasoseptal flap usage rate did not differ between group A (32.7%) and group B (30.6%) (p = 0.79). Postoperative CSF leakage was similar between the two groups (0.63% in group A vs 1.8% in group B, p = 0.57), and the overall rate of CSF leakage was 1.1%. Donor-site complications occurred in 3 patients in group A, including 1 abdominal hematoma, 1 delayed abdominal infection, and 1 fluid collection after fascia lata harvesting. CONCLUSIONS: Collagen matrix implementation significantly decreased autologous graft harvesting without increasing postoperative CSF leakage, contributing to less invasive surgery.

C5a-C5AR1 axis as a potential trigger of the rupture of intracranial aneurysms.

Recent studies have indicated the involvement of neutrophil-mediated inflammatory responses in the process leading to intracranial aneurysm (IA) rupture. Receptors mediating neutrophil recruitment could thus be therapeutic targets of unruptured IAs. In this study, complement C5a receptor 1 (C5AR1) was picked up as a candidate that may cause neutrophil-dependent inflammation in IA lesions from comprehensive gene expression profile data acquired from rat and human samples. The induction of C5AR1 in IA lesions was confirmed by immunohistochemistry; the up-regulations of C5AR1/C5ar1 stemmed from infiltrated neutrophils, which physiologically express C5AR1/C5ar1, and adventitial fibroblasts that induce C5AR1/C5ar1 in human/rat IA lesions. In in vitro experiments using NIH/3T3, a mouse fibroblast-like cell line, induction of C5ar1 was demonstrated by starvation or pharmacological inhibition of mTOR signaling by Torin1. Immunohistochemistry and an experiment in a cell-free system using recombinant C5 protein and recombinant Plasmin indicated that the ligand of C5AR1, C5a, could be produced through the enzymatic digestion by Plasmin in IA lesions. In conclusion, we have identified a potential contribution of the C5a-C5AR1 axis to neutrophil infiltration as well as inflammatory responses in inflammatory cells and fibroblasts of IA lesions. This cascade may become a therapeutic target to prevent the rupture of IAs.

Clinical characteristics of stroke in SARS-CoV-2 infected patients in Japan: A prospective nationwide study.

INTRODUCTION: We investigated the clinical characteristics and outcomes of stroke in SARS-CoV-2 infected patients in Japan. METHODS: This prospective, multicenter observational study of stroke in patients with SARS-CoV-2 infection involving 563 primary stroke centers across Japan was conducted between July 2020, and May 2022. We included 159 stroke cases (131 ischemic stroke, 2 transient ischemic attack (TIA), 21 intracranial hemorrhage, and 5 subarachnoid hemorrhage) and collected their clinical characteristics. Ischemic stroke and TIA (n = 133) were analyzed separately. RESULTS: The mean age of the 159 patients was 70.6 years, with 66% being men. Poor outcomes (modified Rankin Scale score 5-6) occurred in 40% (63/159) at discharge. Among patients with ischemic stroke and TIA, 30%, 18%, 10%, and 42% had cardioembolism, large-artery atherosclerosis, small-vessel occlusion, and cryptogenic stroke or embolic stroke of undetermined source, respectively. One-third (34%) presented with large vessel occlusion (LVO) of the internal carotid, middle cerebral M1, or basilar arteries. Poor outcomes included age (adjusted odds ratio (aOR): 1.06, 95%CI: 1.01-1.12), ischemic heart disease (IHD) history (aOR: 13.00, 95%CI: 1.51-111.70), moderate to severe pneumonia (aOR: 7.78, 95%CI: 1.18-51.42), an National Institutes of Health Stroke Scale score at baseline (aOR: 1.10, 95%CI: 1.03-1.17), LVO (aOR: 14.88, 95%CI: 2.33-94.97), and log10 D-dimer (aOR: 3.38, 95%CI: 1.01-11.26). CONCLUSION: Upon discharge, 40% of SARS-CoV-2 infected patients with ischemic stroke and TIA had poor outcomes. Poor outcomes were associated with older age, IHD history, moderate to severe pneumonia, higher NIHSS scores, LVO, and higher log10 D-dimer. REGISTRATION: UMIN Clinical Trials Registry: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000041226.

Short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE): a multicenter, open-label, randomized clinical trial.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after stent-assisted coil embolization (SACE) for cerebral aneurysm remains uncertain. This randomized trial of short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE) aimed to clarify whether long-term DAPT can reduce the occurrence of ischemic stroke in patients with cerebral aneurysms treated by SACE compared with short-term DAPT. METHODS: Patients treated for cerebral aneurysm with SACE were enrolled from 17 hospitals in Japan. Patients were enrolled within 30 days after SACE and assigned in a 1:1 ratio to receive long-term (12 months) or short-term (3 months) DAPT with aspirin and clopidogrel. Randomization was performed centrally through a web-based system. The primary outcome was the time to ischemic stroke event during 3 to 12 months after SACE. This trial was registered with the Japan Registry of Clinical Trials (jRCTs051180141). RESULTS: A total of 142 patients were recruited from November 4, 2016 to January 7, 2019. Among them, 65 and 68 patients assigned to the long- and short-term DAPT groups, respectively, were included in the full analysis set. Ischemic stroke occurred in no patients in the long-term DAPT group and in one patient in the short-term DAPT group. The incidence rate did not differ between the groups (0.0 vs 2.1/100 person-years; log rank test, P=0.33). CONCLUSIONS: In this multicenter randomized controlled trial, there was not a statistically significant difference in the rate of ischemic strokes between long- and short-term DAPT.

Posterior cerebral artery involvement in unilateral moyamoya disease is exclusively ipsilateral and influenced by RNF213 mutation gene dose: The SUPRA Japan study: PCA involvement in unilateral moyamoya.

OBJECTIVES: The characteristics and clinical implications of posterior cerebral artery (PCA) involvement in unilateral moyamoya disease (U-MMD), such as laterality, frequency of the RNF213 p.R4810K mutation, and clinical outcomes, have not been well studied. POPULATION AND METHODS: We analyzed a cohort of 93 patients with U-MMD who participated in the SUPRA Japan study. Clinical characteristics and radiological examinations were collected from medical records. The presence of the p.R4810K mutation was determined using a TaqMan assay. The clinical outcome was assessed using the modified Rankin Scale (mRS). Univariate and multivariate logistic regression analyses were performed to assess the associations. RESULTS: Among the patients with U-MMD, PCA involvement was observed in 60.0 % (3/5) of patients with homozygous mutation, 11.3 % (7/62) of those with heterozygous mutation, and 3.8 % (1/26) of those with wild type, showing a significant linear trend (p < 0.001 for trend). PCA involvement was observed exclusively on the same side as the affected anterior circulation. Dyslipidemia and cerebral infarction at initial onset were independently associated with mRS ≥1. Hypertension was associated with mRS ≥1 and it was also linked to infarction at initial onset, suggesting a potential confounding effect. Although PCA involvement showed a trend for higher mRS, it was not statistically significant. CONCLUSIONS: Our findings indicate a gene dose effect of the p.R4810K mutation on PCA involvement, with the homozygous state showing the most significant effect. Both genetic and modifiable factors such as dyslipidemia may influence the progression of U-MMD.

Pre-stroke physical activity is associated with post-stroke physical activity and sedentary behavior in the acute phase.

This study investigated the link between pre-stroke and acute-stage physical activity (PA) and sedentary behavior. Forty individuals with stroke (aged 73.6 ± 8.9 years) were enrolled. Post-stroke activity, including metabolic equivalents (METs), sedentary behavior, light PA, and moderate-to-vigorous PA (MVPA), was measured using a tri-axial accelerometer (ActiGraph wGT3X-BT) over 11 consecutive days starting from the 4th day post-stroke. Pre-stroke PA levels were assessed using the International Physical Activity Questionnaire (IPAQ). We measured skeletal muscle mass index (SMI) and phase angle using a bioelectrical impedance analyzer (Inbody S10) upon admission. Physical therapists assessed the Brunnstrom recovery stage (BRS) within 3 days post-stroke. Total daily activity averaged 1.05 ± 0.05 METs. Throughout the day, 91.2 ± 5.1, 7.6 ± 4.1, and 1.2 ± 1.3% was spent in sedentary behavior, light PA, and MVPA, respectively. Only pre-stroke PA was independently associated with METs (ß = 0.66), sedentary behavior (ß = -0.58), light PA (ß = 0.50), and MVPA (ß = 0.71) after adjusting for age, sex, stroke severity, and activities of daily living. This suggests that pre-stroke PA might play a crucial role in reducing sedentary behavior and promoting PA during the acute phase.

Ruptured thrombosed vertebral artery dissecting aneurysm treated with staged flow diverter after prediction of the rupture point by vessel wall MRI.

The safety and feasibility of using staged flow diverter (FD) for ruptured cerebral aneurysms, in which coil embolization is performed in the acute phase and FD is deployed in the subacute phase, has recently been reported. This strategy requires assuming the rupture point and performing coil embolization. Although vessel wall magnetic resonance imaging (VW-MRI) has been reported to be useful in predicting the rupture point of aneurysms, its use with staged FD has not yet been reported. We report the first case of staged FD with preoperative contrast-enhanced VW-MRI to predict the rupture point for partially thrombosed vertebral artery dissecting large aneurysm involving posterior inferior cerebellar artery (PICA) origin. This approach achieved a very good outcome, not only completely occluding the aneurysm, but also reconstructing the parent artery while maintaining the patency of the PICA.

Ruptured brainstem arteriovenous malformation associated with a thalamoperforating artery aneurysm arising from the P1 segment of the right posterior cerebral artery: illustrative case.

BACKGROUND: Cerebral aneurysms of perforating arteries are rare and can be difficult to detect on computed tomography angiography (CTA) and digital subtraction angiography. Treatment is challenging and associated with a significant risk of morbidity. Endovascular treatment of a thalamoperforating artery (TPA) aneurysm within the midbrain has not previously been reported. OBSERVATIONS: A 13-year-old girl with no previous medical history presented with unconsciousness and anisocoria. Head computed tomography showed a right midbrain hemorrhage. CTA showed a midbrain arteriovenous malformation fed by a TPA aneurysm arising from the P1 segment of the right posterior cerebral artery. The feeder had a small distal aneurysm, which increased in size over time. Endovascular embolization was then performed. LESSONS: Cerebral aneurysms of perforating arteries are rare and can be difficult to treat. This is the first report of the endovascular treatment of a TPA aneurysm within the midbrain. Understanding the individual patient's brainstem perforator anatomy and the associated blood flow is essential before occluding a TPA aneurysm to avoid causing ischemia or infarction. Arteriovenous malformation embolization within the brainstem should be avoided because of interperforator anastomoses.

"Transcallosal" periventricular anastomosis in moyamoya disease: the fourth periventricular anastomosis and a potential predictor of hemorrhage.

OBJECTIVES: Choroidal anastomosis is a risk factor for hemorrhage in moyamoya disease. One variant of choroidal anastomosis, "transcallosal anastomosis," originates from the medial posterior choroidal artery, and penetrates the corpus callosum to reconstruct the pericallosal artery. We aimed to investigate the prevalence and the bleeding rate of transcallosal anastomosis using sliding thin-slab maximum intensity projection reformatted from magnetic resonance angiography (MRA). MATERIALS AND METHODS: This study included 222 patients. We defined transcallosal anastomosis grades (0-2) and the stenosis of the anterior (ACA, 0-2), middle (MCA, 1-3), and posterior cerebral artery (PCA, 0-2) by MRA scores, independently by two coauthors. RESULTS: Grade-2 transcallosal anastomosis was detected in 21 patients (9.5 %). There were no correlations of the incidence of transcallosal anastomosis with previous bypass surgery (P = 0.23). Multivariate analysis revealed a significantly higher incidence in hemorrhagic onset and younger age (odds ratio [OR] 3.77, and 0.97). Transcallosal anastomosis had statistically significant correlation with ACA and PCA scores (P = 0.01 and 0.03), but not with MCA scores (P = 0.1). In multivariate analysis, ACA scores 1 and 2 were significantly higher (OR, 15.44 and 11.17), and PCA score 1 was also higher (OR, 3.07), but PCA score 2 was not. Interrater agreement for judgment of transcallosal anastomosis grade was strong (κ = 0.89). Two patients with Grade-2 transcallosal anastomosis had late hemorrhage in the corpus callosum (bleeding rate: 2.5 % per year). CONCLUSIONS: Transcallosal anastomosis may be associated with both advanced ACA and moderate PCA stenosis, and cause hemorrhage at the corpus callosum.

Partially thrombosed giant basilar artery aneurysm with attenuated contrast enhancement of the intraluminal thrombus on vessel wall MRI after flow diversion treatment: illustrative case.

BACKGROUND: The effect of vessel wall magnetic resonance imaging (VW-MRI) enhancement in partially thrombosed aneurysms has previously indicated aneurysmal instability and a rupture risk. However, whether the contrast effect of the wall changes before or after flow diversion treatment is still under investigation. OBSERVATIONS: The authors report a case of a partially thrombosed basilar artery aneurysm that increased in size over a short period, worsened brainstem compression symptoms, and was treated with a flow diverter stent with good results. In this case, VW-MRI after surgery showed a reduced contrast effect on the intraluminal thrombus within the aneurysm. The aneurysm thrombosed and markedly regressed over the next 5 months, with remarkable improvement in the brainstem compression symptoms. LESSONS: This finding on VW-MRI may indicate an attenuation of neovascularization in the thrombus wall and be a sign of aneurysm stabilization.

Vessel wall MRI in moyamoya disease: arterial wall enhancement varies depending on age, arteries, and disease progression.

OBJECTIVE: To investigate the relationship of followings for patients with moyamoya disease (MMD): arterial wall enhancement on vessel wall MRI (VW-MRI), cross-sectional area (CSA), time-of-flight MR angiography (MRA), age, locations from intracranial internal carotid artery (ICA) to proximal middle cerebral artery (MCA), disease progression, and transient ischemic attack (TIA). METHODS: Patients who underwent VW-MRI between October 2018 and December 2020 were enrolled in this retrospective study. We measured arterial wall enhancement (enhancement ratio, ER) and CSA at five sections of ICA and MCA. Also, we scored MRA findings. Multiple linear regression (MLR) analysis was performed to explore the associations between ER, age, MRA score, CSA, history of TIA, and surgical revascularization. RESULTS: We investigated 102 sides of 51 patients with MMD (35 women, 16 men, mean age 31 years ± 18 [standard deviation]). ER for MRA score 2 (signal discontinuity) was higher than ER for other scores in sections D (end of ICA) and E (proximal MCA) on MLR analysis. ER in section E was significantly higher in patients for MRA score 2 with TIA history than without. ER significantly increased as CSA increased in section E, which suggests ER becomes less in decreased CSA due to negative remodeling. CONCLUSION: Arterial wall enhancement in MMD varies by age, location, and disease progression. Arterial wall enhancement may be stronger in the progressive stage of MMD. Arterial wall enhancement increases with history of TIA at proximal MCA, which may indicate the progression of the disease. CLINICAL RELEVANCE STATEMENT: Arterial wall enhancement in moyamoya disease varies by age, location of arteries, and disease progression, and arterial wall enhancement may be used as an imaging biomarker of moyamoya disease. KEY POINTS: It has not been clarified what arterial wall enhancement in moyamoya disease represents. Arterial wall enhancement in moyamoya disease varies by age, location of arteries, and disease progression. Arterial wall enhancement in moyamoya disease increases as the disease progresses.

Seizure control by adding on other anti-seizure medication on seizure during levetiracetam administration in patients with glioma-related epilepsy.

BACKGROUND: Epilepsy is a major symptom in patients with glioma. Levetiracetam (LEV) is recognized as a first-line treatment for glioma-related epilepsy. Increasing the LEV dose is allowed into patients with seizure occurrence against its initial dose. However, the therapeutic efficacy of increasing the LEV dose in response to seizure occurrence remains unclear. METHODS: We retrospectively analyzed 236 glioma patients who were treated with antiseizure medications (ASMs) internally at our institute between September 2010 and December 2017. Of these, the analysis focused on 156 patients treated with LEV who had a clear history of administration. RESULTS: Seizure occurrences were observed in 21 of 75 patients (26.7%) who received LEV as first-line therapy and in 33 of 81 patients (40.7%) who received LEV as non-first-line treatment. The seizure control rate for seizure occurrence with LEV as first-line treatment was significantly higher in patients treated with addition of other ASMs (72.7%) than in those treated with increasing dose of LEV (20.0%) (p = 0.016). The seizure control rate for seizure occurrence with LEV as non-first-line treatment did not differ significantly between patients with addition of other ASMs (58.3%) and those treated with increasing dose of LEV (47.6%) (p = 0.554). CONCLUSIONS: Adding other ASMs was more effective than increasing the LEV dose for seizure control in patients treated with LEV as first-line treatment, but they demonstrated comparable efficacy in patients treated with LEV as non-first-line treatment.

Voxel-based clustered imaging by multiparameter diffusion tensor images for predicting the grade and proliferative activity of meningioma.

INTRODUCTION: Meningiomas are the most common primary central nervous system tumors. Predicting the grade and proliferative activity of meningiomas would influence therapeutic strategies. We aimed to apply the multiple parameters from preoperative diffusion tensor images for predicting meningioma grade and proliferative activity. METHODS: Nineteen patients with low-grade meningiomas and eight with high-grade meningiomas were included. For the prediction of proliferative activity, the patients were divided into two groups: Ki-67 monoclonal antibody labeling index (MIB-1 LI) < 5% (lower MIB-1 LI group; n = 18) and MIB-1 LI ≥ 5% (higher MIB-1 LI group; n = 9). Six features, diffusion-weighted imaging, fractional anisotropy, mean, axial, and radial diffusivities, and raw T2 signal with no diffusion weighting, were extracted as multiple parameters from diffusion tensor imaging. The two-level clustering approach for a self-organizing map followed by the K-means algorithm was applied to cluster a large number of input vectors with the six features. We also validated whether the diffusion tensor-based clustered image (DTcI) was helpful for predicting preoperative meningioma grade or proliferative activity. RESULTS: The sensitivity, specificity, accuracy, and area under the curve of receiver operating characteristic curves from the 16-class DTcIs for differentiating high- and low-grade meningiomas were 0.870, 0.901, 0.891, and 0.959, and those from the 10-class DTcIs for differentiating higher and lower MIB-1 LIs were 0.508, 0.770, 0.683, and 0.694, respectively. The log-ratio values of class numbers 13, 14, 15, and 16 were significantly higher in high-grade meningiomas than in low-grade meningiomas (p < .001). With regard to MIB-1 LIs, the log-ratio values of class numbers 8, 9, and 10 were higher in meningiomas with higher MIB-1 groups (p < .05). CONCLUSION: The multiple diffusion tensor imaging-based parameters from the voxel-based DTcIs can help differentiate between low- and high-grade meningiomas and between lower and higher proliferative activities.

Relation between duration of dual antiplatelet therapy and risk of ischemic stroke after stent-assisted treatment of cerebral aneurysm (DAPTS ACE-registry).

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) in patients with cerebral aneurysm who undergo stent-assisted coil embolization (SACE) has not been established. We aimed to clarify the association between duration of DAPT and incidence of ischemic stroke in patients with cerebral aneurysm. METHODS: We registered patients with cerebral aneurysm who underwent SACE in 27 hospitals in Japan. Those treated with DAPT (aspirin and clopidogrel) were eligible for inclusion in a previously reported randomized control trial (RCT). Patients who were ineligible or refused to participate to the RCT were followed-up for 15 months after SACE as the non-RCT cohort. Our study examined both the RCT and non-RCT cohorts. The primary and secondary outcomes were ischemic stroke and hemorrhagic events. RESULTS: Among the 313 patients registered, 296 were included for analysis (of these, 136 were RCT patients and 160 were non-RCT patients). Patients who were treated with DAPT for more than 6 months (n=191) were classified as the long-term DAPT group. Those treated less than 6 months (n=105) were classified as the short-term group. The incidence of ischemic stroke did not significantly differ between the long-term group (2.5 per 100 person-years) and the short-term group (3.2 per 100 person-years); nor did incidence of hemorrhagic events (0.8 and 3.2 per 100 person-years, respectively). The period of DAPT was not significantly associated with incidence rates of ischemic stroke or hemorrhagic events. CONCLUSIONS: Duration of DAPT was not associated with the incidence of ischemic stroke in the first 15 months after SACE.

Vessel wall imaging and carotid artery stenting for recurrent cervical internal carotid artery vasospasm syndrome: illustrative case.

BACKGROUND: Recurrent cervical internal carotid artery vasospasm syndrome (RCICVS) causes cerebral infarction, ocular symptoms, and occasionally chest pain accompanied by coronary artery vasospasm. The etiology and optimal treatment remain unclear. OBSERVATIONS: The authors report a patient with drug-resistant RCICVS who underwent carotid artery stenting (CAS). Magnetic resonance angiography revealed recurrent vasospasm in the cervical segment of the internal carotid artery (ICA). Vessel wall imaging during an ischemic attack revealed vascular wall thickening of the ICA, similar to that in reversible cerebral vasoconstriction syndrome. The superior cervical ganglion was identified at the anteromedial side of the stenosis site. Coronary artery stenosis was also detected. After CAS, the symptoms of cerebral ischemia were prevented for 2 years, but bilateral ocular and chest symptoms did occur. LESSONS: Vessel wall imaging findings suggest that RCICVS is a sympathetic nervous system-related disease. CAS could be an effective treatment for drug-resistant RCICVS to prevent cerebral ischemic events.

Automatic Ischemic Core Estimation Based on Noncontrast-Enhanced Computed Tomography.

BACKGROUND: Evaluating the extent of ischemic change is an important step in deciding whether to use thrombolysis or mechanical thrombectomy, but the current standard method, Alberta Stroke Program Early CT Score, is semiquantitative and has low consistency among raters. We aim to create and test a fully automated machine learning-based ischemic core segmentation model using only noncontrast-enhanced computed tomography images. METHODS: In this multicenter retrospective study, patients with anterior circulation acute ischemic stroke who received both computed tomography (CT) and magnetic resonance imaging before thrombolysis or recanalization treatment between 2013 and 2019 were included. On CT, the ischemic core was manually delineated using the diffusion-weighted image and apparent diffusion coefficient maps. A deep learning-based ischemic core segmentation model (DL model) was developed using data from 3 institutions (n=272), and the model performance was validated using data from 3 institutions (n=106 Results: The median time ).between CT and magnetic resonance imaging in the validation cohort was 18 min. The DL model calculated ischemic core volume was significantly correlated with the reference standard (intraclass correlation coefficient, 0.90, P<0.01). Both the early time window (≤4.5 hours from onset; intraclass correlation coefficient, 0.90, P<0.01) and the late time window (>4.5 hours from onset; intraclass correlation coefficient, 0.93, P<0.01) had significant correlations. The median difference in ivolume between the model and the reference standard was 4.7 mL (interquartile range, 0.8-12.4 mL). The DL model performed well in distinguishing large ischemic cores (>70 mL), with a sensitivity of 84.2%, specificity of 97.7%, and area under the curve of 0.91. CONCLUSIONS: The deep learning-based ischemic core segmentation model, which was based on noncontrast-enhanced CT, demonstrated high accuracy in assessing ischemic core volume in patients with anterior circulation acute ischemic stroke.

Bioresorbable Poly (L-Lactic Acid) Flow Diverter Versus Cobalt-Chromium Flow Diverter: In Vitro and In Vivo Analysis.

BACKGROUND: Permanent metallic flow diverter (FD) implantation for treatment of intracranial aneurysms requires antiplatelet therapy for an unclear duration and restricts postprocedural endovascular access. Bioresorbable FDs are being developed as a solution to these issues, but the biological reactions and phenomena induced by bioresorbable FDs have not been compared with those of metallic FDs. METHODS: We have developed a bioresorbable poly (L-lactic acid) FD (PLLA-FD) and compared it with an FD composed of cobalt-chromium and platinum-tungsten (CoCr-FD). FD mechanical performance and in vitro degradation of the PLLA-FD were evaluated. For in vivo testing in a rabbit aneurysm model, FDs were implanted at the aneurysm site and the abdominal aorta in the PLLA-FD group (n=21) and CoCr-FD group (n=15). Aneurysm occlusion rate, branch patency, and thrombus formation within the FD were evaluated at 3, 6, and 12 months. Local inflammation and neointima structure were also evaluated. RESULTS: Mean strut, porosity, and pore density for the PLLA-FD were 41.7 µm, 60%, and 20 pores per mm2, respectively. The proportion of aneurysms exhibiting a neck remnant or complete occlusion did not significantly differ between the groups; however, the complete occlusion rate was significantly higher in the PLLA-FD group (48% versus 13%; P=0.0399). Branch occlusion and thrombus formation within the FD were not observed in either group. In the PLLA-FD group, CD68 immunoreactivity was significantly higher, but neointimal thickness decreased over time and did not significantly differ from that of the CoCr-FD at 12 months. Collagen fibers significantly predominated over elastic fibers in the neointima in the PLLA-FD group. The opposite was observed in the CoCr-FD group. CONCLUSIONS: The PLLA-FD was as effective as the CoCr-FD in this study and is feasible for aneurysm treatment. No morphological or pathological problems were observed with PLLA-FD over a 1-year period.

Neuronal Loss in the Bilateral Medial Frontal Lobe Revealed by 123I-iomazenil Single-photon Emission Computed Tomography in Patients with Moyamoya Disease: The First Report from Cognitive Dysfunction Survey of Japanese Patients with Moyamoya Disease (COSMO-Japan Study).

Cognitive impairment in adult patients with moyamoya disease (MMD) is sometimes overlooked and can occur in patients with no ischemic or hemorrhagic lesions. Better profiling and reliable diagnostic methods that characterize the group and associate the impairments and pathology of MMD are required in order to deliver appropriate treatments and support. The potential of 123I-iomazenil single-photon emission computed tomography (SPECT) for this issue has been reported in some studies, but the universality of this method remains unclear. A multicenter study of adult patients (aged 18-60 years) with MMD who experienced difficulties in social lives despite normal activities of daily living was implemented to delineate the common characteristics of this group of patients. In this study, iomazenil SPECT, besides patient characteristics, cognitive functions, and conventional imaging, was acquired to examine whether this method is suitable as a universal diagnostic tool. A total of 36 patients from 12 institutes in Japan were included in this study. Domain scores of world health organization quality of life 26 indicated low self-rating in physical health and psychological domains. The percentages of patients who had <85 in each index were 27.8%-33.3% in the WAIS-III and 16.7%-47.2% in the Wechsler Memory Scale-Revised. The group analysis of iomazenil SPECT demonstrated a decreased accumulation in the bilateral medial frontal areas in comparison with the normal control, whereas there were no specific characteristics on conventional imaging in the cohort. Iomazenil SPECT is a possible universal diagnostic method for the extraction of patients with cognitive impairment in MMD.

Five-Year Stroke Risk and Its Predictors in Asymptomatic Moyamoya Disease: Asymptomatic Moyamoya Registry (AMORE).

BACKGROUND: Long-term outcomes are unknown in patients with asymptomatic moyamoya disease. In this report, we aimed to clarify their 5-year risk of stroke and its predictors. METHODS: We are conducting a multicenter, prospective cohort study (Asymptomatic Moyamoya Registry) in Japan. Participants were eligible if they were 20 to 70 years, had bilateral or unilateral moyamoya disease, experienced no episodes suggestive of TIA and stroke; and were functionally independent (modified Rankin Scale score 0-1). Demographic and radiological information was collected at enrollment. In this study, they are still followed up for 10 years. In this interim analysis, we defined the primary end point as a stroke occurring during a 5-year follow-up period. Independent predictors for stroke were also determined, using a stratification analysis method. RESULTS: Between 2012 and 2015, we enrolled 109 patients, of whom 103 patients with 182 involved hemispheres completed the 5-year follow-up. According to the findings on DSA and MRA, 143 hemispheres were judged as moyamoya disease and 39 hemispheres as questionable manifestations (isolated middle cerebral artery stenosis). The patients with questionable hemispheres were significantly older, more often male, and more frequently had hypertension than those with moyamoya hemisphere. Moyamoya hemispheres developed 7 strokes, including 6 hemorrhagic and 1 ischemic stroke, during the first 5 years. The annual risk of stroke was 1.4% per person, 0.8% per hemisphere, and 1.0% per moyamoya hemisphere. Independent predictor for stroke was Grade-2 choroidal anastomosis (hazard ratio, 5.05 [95% CI, 1.24-20.6]; P=0.023). Furthermore, microbleeds (hazard ratio, 4.89 [95% CI, 1.13-21.3]; P=0.0342) and Grade-2 choroidal anastomosis (hazard ratio, 7.05 [95% CI, 1.62-30.7]; P=0.0093) significantly predicted hemorrhagic stroke. No questionable hemispheres developed any stroke. CONCLUSIONS: The hemispheres with asymptomatic moyamoya disease may carry a 1.0% annual risk of stroke during the first 5 years, the majority of which are hemorrhagic stroke. Grade-2 choroidal anastomosis may predict stroke, and the microbleeds and Grade-2 choroidal anastomosis may carry the risk for hemorrhagic stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: UMIN000006640.