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Purpose: It is difficult to precisely predict indirect bypass development in the context of combined bypass procedures in moyamoya disease (MMD). We aimed to investigate the predictive value of magnetic resonance angiography (MRA) signal intensity in the peripheral portion of the major cerebral arteries for indirect bypass development in adult patients with MMD., Methods: We studied 93 hemispheres from 62 adult patients who underwent combined direct and indirect revascularization between 2005 and 2019 and genetic analysis for RNF213 p.R4810K. The signal intensity of the peripheral portion of the major intracranial arteries during preoperative MRA was graded as a hemispheric MRA score (0-3 in the middle cerebral artery and 0-2 in the anterior cerebral and posterior cerebral arteries, with a high score representing low visibility) according to each vessel's visibility. Postoperative bypass development was qualitatively evaluated using MRA, and we evaluated the correlation between preoperative factors, including the hemispheric MRA score and bypass development, using univariate and multivariate analyses., Results: A good indirect bypass was observed in 70% of the hemispheres. Hemispheric MRA scores were significantly higher in hemispheres with good indirect bypass development than in those with poor indirect bypass development (median: 3 vs. 1; p < 0.0001). Multiple logistic regression analysis revealed hemispheric MRA score as an independent predictor of good indirect bypass development (odds ratio, 2.1; 95% confidence interval, 1.3-3.6; p < 0.01). The low hemispheric MRA score (< 2) and wild-type RNF213 predicted poor indirect bypass development with a specificity of 0.92., Conclusion: Hemispheric MRA score was a predictive factor for indirect bypass development in adult patients who underwent a combined bypass procedure for MMD. Predicting poor indirect bypass development may lead to future tailored bypass surgeries for MMD., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The application of hemoglobin (Hb)-based oxygen carriers (HBOCs) to the treatment of cerebral ischemia has been investigated. A cluster of 1 Hb and 3 human serum albumins (Hb-HSA 3 ) was found to exert neuroprotective effects on ischemia/reperfusion injury. Stroma-free hemoglobin nanoparticles (SFHbNP), a subsequently developed HBOC consisting of a spherical polymerized stroma-free Hb core with a HSA shell, contains the natural antioxidant enzyme catalase and, thus, is expected to exert additive effects. We herein investigated whether SFHbNP exerted enhanced neuroprotective effects in a rat transient middle cerebral artery occlusion (tMCAO) model. Rats were subjected to 2-hour tMCAO and divided into the following 3 groups with the intravenous administration of the respective reagents: (1) phosphate-buffered saline (PBS), as a vehicle (2) Hb-HSA 3 , and (3) SFHbNP. After 24-hour reperfusion, infarct and edema volumes decreased in the order of the PBS, Hb-HSA 3 , and SFHbNP groups, with a significant difference (p < 0.05) between the PBS and SFHbNP groups. Similar reductions were observed in oxidative stress, leukocyte recruitment, and blood-brain barrier disruption in the order of the PBS, Hb-HSA 3 , and SFHbNP groups. In the early phase of reperfusion within 6 h, microvascular HBOC perfusion and cerebral blood flow were maintained at high levels during the reperfusion period in the Hb-HSA 3 and SFHbNP groups. However, a difference was observed in tissue oxygen partial pressure levels, which significantly decreased after 6-hour reperfusion in the Hb-HSA 3 group, but remained high in the SFHbNP group. A superior oxygen transport ability appears to be related to the enhanced neuroprotective effects of SFHbNP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Delayed foreign body reactions to either or both clipping and coating materials have been reported in several small series; however, studies in the titanium clip era are scarce. This study aims to survey the contemporary status of such reactions to titanium clips and coating materials. Among patients who received a total of 2327 unruptured cerebral aneurysmal surgeries, 12 developed delayed intraparenchymal reactions during outpatient magnetic resonance imaging (MRI) follow-up. A retrospective investigation was conducted. The patients' average age was 58.6 (45-73) years, and 11 were women. The aneurysms were located in the middle cerebral artery (n = 7), internal carotid artery (n = 4), or anterior communicating artery (AComA, n = 1). In 10 patients, additional coating with tiny cotton fragments was applied to the residual neck after clipping with titanium clips; however, only the clipping with titanium clips was performed in the remaining two. The median time from surgery to diagnosis was 4.5 (0.3-60) months. Seven (58.3%) patients were asymptomatic, and three developed neurological deficits. MRI findings were characterized by a solid- or rim-enhancing lobulated mass adjacent to the clip with surrounding parenchymal edema. In 11 patients, the lesions reduced in size or disappeared; however, in one patient, an AComA aneurysm was exacerbated, necessitating its removal along with optic nerve decompression. In conclusion, cotton material is a strongly suspected cause of delayed foreign body reactions, and although extremely rare, titanium clips alone may also induce such a reaction. The prognosis is relatively good with steroid therapy; however, caution is required when the aneurysm is close to the optic nerve, as in AComA aneurysms.

Background:  There are some cases where a radial artery (RA) graft is needed for a high-flow extracranial to intracranial (EC-IC) bypass as the external carotid artery (ECA) cannot be utilized as a donor artery. In this report, we describe two cases of extracranial vertebral artery (VA) to middle cerebral artery (MCA) high-flow bypass using an RA graft with an artificial vessel as an alternative bypass technique., Methods:  The patient was placed supine with a head rotation of 80 degrees. After frontotemporal craniotomy, another C: -shaped skin incision was made at the retroauricular region and the V3 portion of the VA was exposed at the suboccipital triangle. Prior to attempting the high-flow bypass, the superficial temporal artery (STA) was anastomosed to the M4 portion of the MCA as an insurance bypass. The RA graft was anastomosed to the V3 portion of the VA that traveled under the periosteum at the supra-auricular region through an artificial vessel. After RA-M2 anastomosis, an alternative EC-IC bypass, the V3-RA-M2 bypass, was achieved., Results:  Postoperative angiography demonstrated successful graft patency and no perioperative complications were observed in both cases., Conclusions:  In the cases where a high-flow bypass is required, the V3 portion of the VA is a suitable alternative proximal anastomosis site when the ECA is not a candidate donor. Furthermore, an artificial vessel shows satisfactory protection against graft complications., Competing Interests: None declared., (Thieme. All rights reserved.)

A cortical hyperintensity on fluid-attenuated inversion recovery images (FLAIR cortical hyperintensity (FCH)) is an abnormal finding after revascularization surgery for moyamoya disease. This study aimed to investigate the pathophysiology of FCH through genetic analyses of RNF213 p.R4810K polymorphism and perioperative hemodynamic studies using single-photon emission computed tomography. We studied 96 hemispheres in 65 adults and 47 hemispheres in 27 children, who underwent combined direct and indirect revascularization. Early or late FCH was defined when it was observed on postoperative days 0-2 and 6-9, respectively. FCH scores (range: 0-6) were evaluated according to the extent of FCH in the operated hemisphere. FCHs were significantly more prevalent in adult patients than pediatric patients (early: 94% vs. 78%; late: 97% vs. 59%). In pediatric patients, FCH scores were significantly improved from the early to late phase regardless of the RNF213 genotype (mutant median [IQR]: 2 [1-5] vs. 1 [0-2]; wild-type median: 4 [0.5-6] vs. 0.5 [0-1.75]). In adults, FCH scores were significantly improved in patients with the wild-type RNF213 allele (median: 4 [2-5.25] vs. 2 [2, 3]); however, they showed no significant improvement in patients with the RNF213 mutation. FCH scores were significantly higher in patients with symptomatic cerebral hyperperfusion than those without it (early median: 5 [4, 5] vs. 4 [2-5]; late median: 4 [3-5] vs. 3 [2-4]). In conclusion, the RNF213 p.R4810K polymorphism was associated with prolonged FCH, and extensive FCH was associated with symptomatic cerebral hyperperfusion in adult patients with moyamoya disease., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Direct superficial temporal artery (STA) to middle cerebral artery (MCA) anastomosis combined with indirect pial synangiosis provides favorable surgical collaterals for Moyamoya disease (MMD), especially in adults; however, factors leading to the development of each direct and indirect collateral are not well documented.We aimed to investigate the association between RNF213 founder polymorphism (p.R4810K) and each direct and indirect collateral development. By qualitative and quantitative evaluations of direct and indirect surgical collaterals using time-of-flight MR angiography, postoperative development of each type of bypass was evaluated independently into two categories. Multivariate logistic regression analysis was performed to study the contributing factors for the development of each surgical collateral. Excellent development of postoperative direct and indirect bypass was observed in 65 hemispheres (70%) by qualitative evaluation, which was confirmed by quantitative evaluation. Multivariate logistic regression analysis of excellent indirect bypass development revealed a significant positive correlation with the p.R4810K (odds ratio, OR4.0; 95%-confidence interval, CI 1.2-16), advanced MR angiographic stage (OR9.5; 95%CI 1.7-73), and preoperative middle meningeal artery caliber (OR6.8; 95%CI 1.8-35), but a significant negative correlation was found with the excellent direct bypass development (OR0.17; 95%CI 0.03-0.75). No significant correlation was observed between excellent direct bypass development and the p.R4810K (OR0.95; 95%CI 0.37-2.4).In conclusion, excellent development of indirect collaterals after STA-MCA anastomosis combined with indirect pial synangiosis occurs more frequently in adult MMD with the RNF213 founder polymorphism, suggesting a role of the p.R4810K variant for marked in-growth of indirect collaterals and the utility of preoperative genetic analysis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Lenticulostriate artery (LSA) aneurysm is relatively rare, and the need for surgical intervention is controversial. Here, we report a case of ruptured LSA aneurysm which was accompanied by familial Mediterranean fever (FMF). A 45-year-old woman with a history of FMF presented with sudden onset of headache and vertigo. Computed tomography revealed hemorrhage in the right caudate nucleus and lateral ventricles. Digital subtraction angiography revealed a fusiform aneurysm (3mm) at the distal site of medial LSA. Observation was selected, and the aneurysm gradually decreased and eventually disappeared on the 105 th day from the onset. This was the first report describing an LSA aneurysm associated with FMF. It suggests that such aneurysms could be treated conservatively with close radiological follow-up.

Objective: The surgical resection of craniovertebral junction(CVJ)meningioma is challenging because of the neighboring brainstem, lower cranial nerves, and vertebral artery(VA). Moreover, encasement of the VA by the tumor can raise the risk of complications and require cautious manipulation during surgery., Case: A 46-year-old woman presented with a one-year history of neck pain. She had temporal hemiplegia and numbness on her left side. Magnetic resonance imaging(MRI)showed a CVJ meningioma pushing the brainstem from the right vertebral side and encasing the right VA. Digital subtraction angiography(DSA)showed two feeding arteries arising from the right VA and a sunburst sign. The right VA was the dominant side but did not have the right posterior inferior cerebellar artery(PICA). The anterior spinal artery(ASA)was dominant in the left VA. We performed a balloon test occlusion(BTO)for 20 min and it did not cause any complications;therefore, we occluded the VA using endovascular coils. After 4 days, we removed the meningioma in the prone position, using a far-lateral approach and C1-laminectomy. The laterally located meningioma pushed the brainstem. After detaching the tumor from the dura, we cut the encased VA and the tumor was resected safely(Simpson grade II). Postoperatively, she developed temporal thermal hypoalgesia on the left side of her body. Magnetic resonance imaging showed a microinfarction in the medulla., Conclusion: If the VA test occlusion provides a clear result, pre-operative endovascular sacrifice of the VA encased by CVJ meningioma is a feasible treatment strategy.

Objective: In combined revascularization surgery for patients with moyamoya disease, intracerebral hemorrhage (ICH) during the postoperative acute phase is a rarely observed but severe complication. Its clinical features remain unclear because of its low incidence rate. The aim of this study was to clarify the clinical characteristics of immediate postoperative ICH., Methods: The frequency, onset timing, and hematoma location of patients who demonstrated immediate postoperative ICH were investigated in 201 consecutive surgeries performed in 134 patients. Associations between immediate postoperative ICH and demographics, clinical presentation type, perioperative blood pressure (BP), and neuroimaging data were analyzed., Results: Postoperative ICH was observed in 6 cases (2.99%; mean age, 46.0 ± 7.6 years). The onset timing of ICH was within 24 hours after surgery in most patients (83.3%). Hematomas were located at the subcortical lesion beneath the anastomosed cortex (n = 5) and caudate head (n = 1). Three cases (50.0%) required hematoma evacuation. A higher age at surgery was associated with postoperative ICH (P = 0.046). In adult cases (132 surgeries, 65.7%), hemorrhagic presentation at onset (P = 0.0027) and an increase in BP from pre- to postoperative stage (systolic BP increase: P = 0.0058, diastolic BP increase: P = 0.0274) were significantly associated with postoperative ICH., Conclusions: The results suggest that older patients, with hemorrhagic presentation and greater postoperative BP increase, should be carefully managed to avoid postoperative ICH. Immediate hematoma evacuation may be effective in preventing devastating outcomes after postoperative ICH., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Microglia of the central nervous system act as sentinels and rapidly react to infection or inflammation. The pathophysiological role of bone marrow-derived microglia is of particular interest because they affect neurodegenerative disorders and neuropathic pain. The hypothesis of the current study is that chronic psychological stress (chronic PS) induces the infiltration of bone marrow-derived microglia into hypothalamus by means of chemokine axes in brain and bone marrow., Methods and Findings: Here we show that bone marrow-derived microglia specifically infiltrate the paraventricular nucleus (PVN) of mice that received chronic PS. Bone marrow derived-microglia are CX3CR1(low)CCR2(+)CXCR4(high), as distinct from CX3CR1(high)CCR2(-)CXCR4(low) resident microglia, and express higher levels of interleukin-1β (IL-1β) but lower levels of tumor necrosis factor-α (TNF-α). Chronic PS stimulates the expression of monocyte chemotactic protein-1 (MCP-1) in PVN neurons, reduces stromal cell-derived factor-1 (SDF-1) in the bone marrow and increases the frequency of CXCR4(+) monocytes in peripheral circulation. And then a chemokine (C-C motif) receptor 2 (CCR2) or a β3-adrenoceptor blockade prevents infiltration of bone marrow-derived microglia in the PVN., Conclusion: Chronic PS induces the infiltration of bone marrow-derived microglia into PVN, and it is conceivable that the MCP-1/CCR2 axis in PVN and the SDF-1/CXCR4 axis in bone marrow are involved in this mechanism.