Recent Translational Research Models of Intracranial Atherosclerotic Disease.

Intracranial atherosclerotic disease (ICAD) is a leading cause of ischemic stroke worldwide. However, research on the pathophysiology of ICAD is scarce due to the relative inaccessibility of histology samples and the lack of comprehensive experimental models. As a result, much of the current understanding of ICAD relies on research on extracranial atherosclerosis. This approach is problematic as intracranial and extracranial arteries are anatomically, structurally, physiologically, and metabolically distinct, indicating that intracranial and extracranial atherosclerosis likely develop through different biologic pathways. The current standard of care for ICAD treatment relies predominantly on therapeutics developed to treat extracranial atherosclerosis and is insufficient given the alarmingly high risk of stroke. To provide a definitive treatment for the disease, a deeper understanding of the pathophysiology underlying ICAD is specifically required. True mechanistic understanding of disease pathogenesis is only possible using robust experimental models. In this review, we aim to identify the advantages and limitations of the existing in vivo and in vitro models of ICAD and basic atherosclerotic processes, which may be used to inform better models of ICAD in the future and drive new therapeutic strategies to reduce stroke risk.

Clinical presentation and treatment of 26 spinal epidural arteriovenous fistulas: a single-center experience.

BACKGROUND: Spinal epidural arteriovenous fistulas (SEDAVFs) are rarely diagnosed vascular malformations that can cause spinal cord compression and congestive myelopathy. METHODS: This is a single-center, retrospective case series of patients with SEDAVFs who underwent observation or treatment at UCLA medical center between 1993 and 2023. RESULTS: Between 1993 and 2023 a total of 26 patients at UCLA were found to have a SEDAVF. The median age at treatment was 59 years (range 4 months to 91 years). Compared with sacral, lumbar, and thoracic SEDAVFs, patients with cervical SEDAVF were younger (41 years vs 63 years, P=0.016) and more likely to be female (66.7% vs 14.3%, P=0.006). Possible triggers for development of SEDAVFs may be prior spinal surgery or trauma (n=4), turning the neck (n=1), lifting a heavy box (n=1), a prolonged period of bending over (n=1), and neurofibromatosis type 1 (n=1). Of the 22 patients treated endovascularly, 18 (82%) were angiographically cured on the first attempt without complications. One patient underwent surgical treatment alone and had a failed surgery on the first attempt, and developed a surgical site infection after the second successful attempt at treatment. Of the 16 patients with adequate clinical follow-up, 11 (69%) demonstrated early improved clinical outcome (eg, improved strength on examination, absent bruit). CONCLUSIONS: SEDAVFs are a rarely diagnosed disease that can be treated effectively and safely with endovascular embolization in most cases. Patients with sacral, lumbar, and thoracic SEDAVFs were older and more often male compared to patients with cervical SEDAVFs.

Estimating Bridge Natural Frequencies Based on Modal Analysis of Vehicle-Bridge Synchronized Vibration Data.

This paper presents a method for accurately estimating the natural frequencies of bridges by simultaneously measuring the acceleration vibration data of vehicles and bridges and applying modal analysis theory. Vibration sensors synchronized with GPS timing were installed on both vehicles and bridges, achieving stable and high-precision time synchronization. This enabled the computation of the bridge's Frequency Response Functions (FRFs) for each mode, leading to a refined estimation of natural frequencies. The validity of the theory was confirmed through numerical simulations and experimental tests. The simulations confirmed its effectiveness, and similar trends were observed in actual bridge measurements. Consequently, this method significantly enhances the feasibility of bridge health monitoring systems. The proposed method is suitable for road bridges with spans ranging from short- to medium-span length, where the vehicle is capable of exciting the bridge.

Expansion of CD4+ cytotoxic T lymphocytes with specific gene expression patterns may contribute to suppression of tumor immunity in oral squamous cell carcinoma: single-cell analysis and in vitro experiments.

Background: Cancer immunotherapy targeting CD8+ T cells has made remarkable progress, even for oral squamous cell carcinoma (OSCC), a heterogeneous epithelial tumor without a substantial increase in the overall survival rate over the past decade. However, the therapeutic effects remain limited due to therapy resistance. Thus, a more comprehensive understanding of the roles of CD4+ T cells and B cells is crucial for more robust development of cancer immunotherapy. Methods: In this study, we examined immune responses and effector functions of CD4+ T cells, CD8+ T cells and B cells infiltrating in OSCC lesions using single-cell RNA sequencing analysis, T cell receptor (TCR) and B cell receptor (BCR) repertoire sequencing analysis, and multi-color immunofluorescence staining. Finally, two Kaplan-Meier curves and several Cox proportional hazards models were constructed for the survival analysis. Results: We observed expansion of CD4+ cytotoxic T lymphocytes (CTLs) expressing granzymes, which are reported to induce cell apoptosis, with a unique gene expression patterns. CD4+ CTLs also expressed CXCL13, which is a B cell chemoattractant. Cell-cell communication analysis and multi-color immunofluorescence staining demonstrated potential interactions between CD4+ CTLs and B cells, particularly IgD- CD27- double negative (DN) B cells. Expansion of CD4+ CTLs, DN B cells, and their contacts has been reported in T and B cell-activated diseases, including IgG4-related disease and COVID-19. Notably, we observed upregulation of several inhibitory receptor genes including CTLA-4 in CD4+ CTLs, which possibly dampened T and B cell activity. We next demonstrated comprehensive delineation of the potential for CD8+ T cell differentiation towards dysfunctional states. Furthermore, prognostic analysis revealed unfavorable outcomes of patients with a high proportion of CD4+ CTLs in OSCC lesions. Conclusion: Our study provides a dynamic landscape of lymphocytes and demonstrates a systemic investigation of CD4+ CTL effects infiltrating into OSCC lesions, which may share some pathogenesis reported in severe T and B cell-activated diseases such as autoimmune and infectious diseases.

Implants Placed with a Ring Technique Using Inlay and Onlay Block Xenografts in the Mandible of Rabbits.

BACKGROUND: Xenogenous bone has been proposed as an alternative to overcome the disadvantages of autogenous grafting. The aim of the present study was to study bone dynamics at inlay and onlay xenografts used for bone augmentation applying a ring technique. METHODS: The bone at the lateral surface of the mandibular angle of 12 adult male New Zealand White rabbits was exposed bilaterally. The cortical layer received multiple perforations on one side of the mandible, and a xenograft block of collagenated cancellous equine bone, 7 mm in diameter and 3 mm in width, was fixed on the prepared surface using an implant (onlay group). On the opposite side, a defect 7 mm in diameter and 3 mm in depth was prepared, and the xenograft block was adapted to the defect and fixed with an implant (inlay group). RESULTS: After ten weeks of healing, in the onlay grafts, new bone was mainly formed on the trabeculae surface, reaching in some specimens the most coronal regions of the block. In the inlay grafts, new bone was found arranged on the trabecular surfaces but also occupying the spaces among the trabeculae. The entrance of the defect was often found close to the top of the block by newly formed bone. A higher percentage of new bone was found in the inlay (19.0 ± 9.3%) compared to the onlay (10.4 ± 7.4%) groups (p = 0.031). The mean gain in osseointegration at the implant in relation to the base of the original 3 mm deep defect was 0.95 ± 1.05% in the onlay group and 0.78 ± 0.71% in the inlay group (p = 0.603). CONCLUSION: The inlay grafts exhibited a higher new bone percentage than the onlay block grafts possibly due to the defect conformation that presented more sources for bone growth. The trabecular conformation and the composition of the grafts made possible the expression of the osteoconductive properties of the material used. This resulted, in several specimens, in the growth of bone on the graft trabeculae toward the most superior regions in both groups and in the closure of the coronal entrance of the defects in the inlay group. The clinical relevance of this experiment is that the ring technique applied as an inlay method could be suitable for bone augmentation.

Devices and Techniques.

This extensive review explores the intricacies of the three principal mechanical thrombectomy techniques: the stent retriever technique, contact aspiration technique, and a combined approach, and their application in managing acute ischemic stroke. Each technique operates uniquely on the thrombus, leading to differences in their efficacy. Factors including clot size, clot stiffness, vessel tortuosity, and the angle of interaction between the aspiration catheter and the clot significantly influence these differences. Clinical trials and meta-analyses have shown the overall equivalency of these techniques for the treatments of large vessel occlusion and distal medium vessel occlusions. However, there are nuanced differences that emerge under specific clinical circumstances, highlighting the absence of a one-size-fits-all strategy in acute ischemic stroke management. We emphasize the need for future investigations to elucidate these nuances further, aiming to refine procedural strategies and individualize patient care for optimal outcomes.

Toll-like receptor 9-positive plasmacytoid dendritic cells promote Th17 immune responses in oral lichen planus stimulated by epithelium-derived cathepsin K.

Oral lichen planus (OLP) is a chronic inflammatory disease associated with T cell infiltration. The crosstalk between oral epithelium and mucosal T cells was considered to be crucial in the pathogenesis of OLP. Here, we selectively extracted the normal epithelium (NE) and lesional epithelium (LE) of buccal mucosa specimens from three patients with OLP by laser capture microdissection due to identify the pathogenic factors. Cathepsin K (CTSK) was identified as one of common upregulated genes in the LE by DNA microarray. Immunohistochemically, CTSK was distinctly detected in and around the LE, while it was rarely seen in the NE. Recent studies showed that CTSK enhanced Toll-like receptor 9 (TLR9) signaling in antigen-presenting cells, leading to Th17 cell differentiation. TLR9 expression mainly co-localized with CD123+ plasmacytoid dendritic cells (pDCs). The number of RORγt-positive cells correlated with that of CTSK-positive cells in OLP tissues. CD123+ pDCs induced the production of Th17-related cytokines (IL-6, IL-23, and TGF-ß) upon stimulation with TLR9 agonist CpG DNA. Moreover, single cell RNA-sequencing analysis revealed that TLR9-positive pDCs enhanced in genes associated with Th17 cell differentiation in comparison with TLR9-negative pDCs. CTSK could induce Th17-related production of CD123+ pDCs via TLR9 signaling to promote the pathogenesis of OLP.

Intermittent Orbital Pain due to Hemodynamic Collapse of an Orbital Varix: A Case Report.

Orbital varices typically present with symptoms related to dilation or thrombosis. We describe a rare presentation of an orbital varix with pain caused by hemodynamic collapse of the varix. A woman in the third decade presented with position-dependent orbital pain and enophthalmos. She was found to have an intraorbital varix and a separate pterygoid varix. The patient underwent endovascular treatment of the pterygoid varix using coils and sclerosing agents which altered the venous outflow from the orbital varix. The patient had immediate resolution of symptoms after the procedure. Our findings suggest that extraorbital venous outflow abnormalities may be the cause of symptoms in selected cases of orbital varices. By understanding the venous structures on cerebral angiography and treating the extraorbital component, orbital intervention may be avoided, reducing the risk of complications.

In vitro comparison of manual and robotic endovascular thrombectomy for acute ischemic stroke.

BACKGROUND: Robotic endovascular systems have the potential to reduce radiation exposure to physicians and expand timely neurointerventional access to patients in remote areas. The goal of the study was to determine the feasibility of robotic endovascular thrombectomy (EVT) in an in vitro model. METHODS: In vitro procedures were conducted manually and robotically using the Corpath GRX robotic system in a human vascular simulator with an elastic ovine clot in the M1 segment of the left middle cerebral artery. Due to the limited device compatibility of the CorPath GRX, a simple technique with a stent retriever and guiding catheter without a balloon was used in the study. Seven robotic EVT and manual EVT were carried out in each group. Metrics including procedural time, success rate, and radiation dose were compared between the two groups. RESULTS: In robotic EVT, the mean total preparation and procedural time was 892 s, which was significantly longer than manual operation at 357 (p = 0.0001). There was no significant difference in the success rate between the two approaches (robotic: 28.6% vs. manual 42.9%, p = 0.577). The mean radiation exposure to operating physicians was significantly lower during robotic operation compared to manual operation (0.02 µSv vs. 0.22 µSv, p < 0.0001). CONCLUSIONS: Robotic EVT was feasible in our human vascular simulator with significantly reduced radiation exposure to the operating physicians, despite an increased length of procedure when compared to manual procedures. Future technological advancement is warranted for reducing procedural length using endovascular robotic techniques.

Hemostatic patch with ultra-strengthened mechanical properties for efficient adhesion to wet surfaces.

Controlling traumatic bleeding from damaged internal organs while effectively sealing the wound is critical for saving the lives of patients. Existing bioadhesives suffer from blood incompatibility, insufficient adhesion to wet surfaces, weak mechanical properties, and complex application procedures. Here, we engineered a ready-to-use hemostatic bioadhesive with ultra-strengthened mechanical properties and fatigue resistance, robust adhesion to wet tissues within a few seconds of gentle pressing, deformability to accommodate physiological function and action, and the ability to stop bleeding efficiently. The engineered hydrogel, which demonstrated high elasticity (>900%) and toughness (>4600 kJ/m3), was formed by fine-tuning a series of molecular interactions and crosslinking mechanisms involving N-hydroxysuccinimide (NHS) conjugated alginate (Alg-NHS), poly (ethylene glycol) diacrylate (PEGDA), tannic acid (TA), and Fe3+ ions. Dual adhesive moieties including mussel-inspired pyrogallol/catechol and NHS synergistically enhanced wet tissue adhesion (>400 kPa in a wound closure test). In conjunction with physical sealing, the high affinity of TA/Fe3+ for blood could further augment hemostasis. The engineered bioadhesive demonstrated excellent in vitro and in vivo biocompatibility as well as improved hemostatic efficacy as compared to commercial Surgicel®. Overall, the hydrogel design strategy described herein holds great promise for overcoming existing obstacles impeding clinical translation of engineered hemostatic bioadhesives.

Robotic Diagnostic Cerebral Angiography: A Multicenter Experience of 113 Patients.

BACKGROUND: Neurointerventional robotic systems have potential to reduce occupational radiation, improve procedural precision, and allow for future remote teleoperation. A limited number of single institution case reports and series have been published outlining the safety and feasibility of robot-assisted diagnostic cerebral angiography. METHODS: This is a multicenter, retrospective case series of patients undergoing diagnostic cerebral angiography at three separate institutions - University of California, Davis (UCD); University of California, Los Angeles (UCLA); and University of California, San Francisco (UCSF). The equipment used was the CorPath GRX Robotic System (Corindus, Waltham, MA). RESULTS: A total of 113 cases were analyzed who underwent robot-assisted diagnostic cerebral angiography from September 28, 2020 to October 27, 2022. There were no significant complications related to use of the robotic system including stroke, arterial dissection, bleeding, or pseudoaneurysm formation at the access site. Using the robotic system, 88 of 113 (77.9%) cases were completed successfully without unplanned manual conversion. The principal causes for unplanned manual conversion included challenging anatomy, technical difficulty with the bedside robotic cassette, and hubbing out of the robotic system due to limited working length. For robotic operation, average fluoroscopy time was 13.2 min (interquartile range (IQR), 9.3 to 16.8 min) and average cumulative air kerma was 975.8 mGY (IQR, 350.8 to 1073.5 mGy). CONCLUSIONS: Robotic cerebral angiography with the CorPath GRX Robotic System is safe and easily learned by novice users without much prior manual experience. However, there are technical limitations such as a short working length and an inability to support 0.035" wires which may limit its widespread adoption in clinical practice.

Computational fluid dynamics-based virtual angiograms for the detection of flow stagnation in intracranial aneurysms.

The goal of this study was to test if CFD-based virtual angiograms could be used to automatically discriminate between intracranial aneurysms (IAs) with and without flow stagnation. Time density curves (TDC) were extracted from patient digital subtraction angiography (DSA) image sequences by computing the average gray level intensity inside the aneurysm region and used to define injection profiles for each subject. Subject-specific 3D models were reconstructed from 3D rotational angiography (3DRA) and computational fluid dynamics (CFD) simulations were performed to simulate the blood flow inside IAs. Transport equations were solved numerically to simulate the dynamics of contrast injection into the parent arteries and IAs and then the contrast retention time (RET) was calculated. The importance of gravitational pooling of contrast agent within the aneurysm was evaluated by modeling contrast agent and blood as a mixture of two fluids with different densities and viscosities. Virtual angiograms can reproduce DSA sequences if the correct injection profile is used. RET can identify aneurysms with significant flow stagnation even when the injection profile is not known. Using a small sample of 14 IAs of which seven were previously classified as having flow stagnation, it was found that a threshold RET value of 0.46 s can successfully identify flow stagnation. CFD-based prediction of stagnation was in more than 90% agreement with independent visual DSA assessment of stagnation in a second sample of 34 IAs. While gravitational pooling prolonged contrast retention time it did not affect the predictive capabilities of RET. CFD-based virtual angiograms can detect flow stagnation in IAs and can be used to automatically identify aneurysms with flow stagnation even without including gravitational effects on contrast agents.

Extrafollicular IgD-CD27-CXCR5-CD11c- DN3 B cells infiltrate inflamed tissues in autoimmune fibrosis and in severe COVID-19.

Although therapeutic B cell depletion dramatically resolves inflammation in many diseases in which antibodies appear not to play a central role, distinct extrafollicular pathogenic B cell subsets that accumulate in disease lesions have hitherto not been identified. The circulating immunoglobulin D (IgD)-CD27-CXCR5-CD11c+ DN2 B cell subset has been previously studied in some autoimmune diseases. A distinct IgD-CD27-CXCR5-CD11c- DN3 B cell subset accumulates in the blood both in IgG4-related disease, an autoimmune disease in which inflammation and fibrosis can be reversed by B cell depletion, and in severe COVID-19. These DN3 B cells prominently accumulate in the end organs of IgG4-related disease and in lung lesions in COVID-19, and double-negative B cells prominently cluster with CD4+ T cells in these lesions. Extrafollicular DN3 B cells may participate in tissue inflammation and fibrosis in autoimmune fibrotic diseases, as well as in COVID-19.

Effect of Arginine Vasopressin on Intraoperative Hypotension Caused by Oral Administration of 5-Aminolevulinic Acid.

5-Aminolevulinic acid (5-ALA) is used for the photodynamic diagnosis of malignant tumors and has been effectively utilized to improve the complete resection rate and reduce the risk of tumor recurrence. However, intraoperative hypotension is a common adverse effect of oral 5-ALA, and it occasionally progresses to severe prolonged hypotension requiring high-dose catecholamine administration. We report a case of intraoperative hypotension due to oral 5-ALA in which arginine vasopressin (AVP) administration was effective for increasing the blood pressure. A 77-year-old man scheduled for a craniotomy for glioma was administered 5-ALA orally before surgery. After the induction of anesthesia, his blood pressure decreased substantially. Although we administered various vasopressor agents, hypotension was prolonged. However, after starting a continuous administration of AVP, the systolic blood pressure increased, and the hemodynamic parameters remained stable during the remainder of the operation. 5-ALA administration may lower blood pressure by inducing nitric oxide production, and AVP inhibits inducible nitric oxide synthase messenger RNA expression and interleukin-1ß-stimulated nitric oxide production. In light of these mechanisms, AVP may be a reasonable treatment agent for hypotension induced by 5-ALA.

Aneurysmal subarachnoid hemorrhage in pregnancy: National trends of treatment, predictors, and outcomes.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) is a rare event associated with significant pregnancy-associated maternal and neonatal morbidity and mortality. The optimal treatment strategy and clinical outcome of aSAH in pregnancy remains unclear. We aimed to investigate the treatment utilizations and outcomes of aSAH in pregnant people. METHODS: Using the 2010-2018 National Inpatient Sample, we identified all birth hospitalizations of women between ages of 18 to 45 associated with subarachnoid hemorrhage and aneurysm treatment were included. Multivariate analyses were used to evaluate the effect of pregnancy state, mode of treatment of aneurysms, severity of subarachnoid hemorrhage on mortality and discharge destination of this cohort. Trends in mode of treatment utilized for aneurysmal treatment in this time interval was evaluated. RESULTS: 13,351 aSAH with treatment were identified, of which 440 were associated with pregnancy. There was no significant difference in mortality or rate of discharge to home in pregnancy related hospitalization. Worse aSAH severity, chronic hypertension, and smaller hospital size was associated with significantly higher rate of mortality from aSAH during pregnancy. Worse aSAH severity was associated with lower rate of discharge to home. Like the non-pregnant cohort, the treatment of ruptured aneurysms in pregnancy are increasingly through endovascular approaches. The mode of treatment does not change the mortality or discharge destination. CONCLUSIONS: Pregnancy does not alter mortality or the discharge destination for aSAH. Ruptured aneurysms during pregnancy are increasingly treated endovascularly. Mode of aneurysm treatment does not affect mortality or discharge destination in pregnancy.

First-in-human trial of Center Wire for neuroendovascular therapy to avoid guidewire-related complications.

BACKGROUND: An exchange maneuver is useful for the delivery of devices to target vessels. However, hemorrhagic complications can occur due to vessel perforation during an exchange maneuver. In addition, the exchange is often challenging due to unfavorable anatomy. Center Wire is an exchange-length wire with a nondetachable stent that was developed to improve navigation and stability during exchange maneuvers. The aim of this study is to investigate the safety and efficacy of Center Wire of the anchor wire technique during neuroendovascular treatment. METHODS: Ten patients with intracranial aneurysms were treated after signing a Certified Review Board-approved consent. Anchor wire technique was used in all patients to navigate catheters to the target vessel for aneurysm treatment. RESULTS: Anchor wire technique was successfully applied in all 10 cases using Center Wire. One device-related incident of vasospasm occurred which was asymptomatic. No device-related dissection, perforation, or thromboembolic events occurred. One patient had intraoperative aneurysm rupture during coil placement which was treated immediately without clinical consequences. Two patients had postoperative ischemic strokes due to thrombotic occlusion of branches originating from the aneurysm which were unrelated to the device. CONCLUSIONS: This first-in-human trial of Center Wire demonstrated the safety and efficacy of the anchor wire technique for neuroendovascular treatment in a strictly regulated prospective registry trial.

First-in-human trial of Stabilizer device in neuroendovascular therapy.

Objectives: Flow diverter or stent implantation to intracranial target lesion requires large inner diameter microcatheter navigation. The exchange method using stiff long wire is often necessary if it is difficult to navigate over the regular guidewire. However, this method has an intrinsic risk of vessel damage and may cause severe complications. We investigated the safety and efficacy of a new device, the Stabilizer device for navigation in a first-in-human clinical trial under the Certified Review Board agreement. Materials and methods: The Stabilizer is a 320 cm length exchange wire with a stent for anchoring and is compatible with a 0.0165" microcatheter. The trial design is a prospective single-arm open-label registry. Inclusion criteria are elective flow diverter treatment or stent-assisted coiling, expected to be difficult to navigate a microcatheter with a regular micro guidewire, and obtained documented consent. The primary endpoint of the study was a hemorrhagic complication. Results: Five patients were enrolled in this trial. The median age is 52 years, ranges from 41 to 70, and all patients were female. Three aneurysms were located on the internal carotid artery, one on the vertebral artery, and one on the basilar artery. Basilar artery aneurysm was treated by stent-assisted coiling and others were treated by flow diverter deployment. All cases successfully navigate microcatheter for the treatment by the trial method using Stabilizer device without any adverse event. Conclusions: The results from this first-in-human consecutive five cases show the safety of the Stabilizer device in neuro-endovascular therapy for navigation of devices to the intracranial target lesion.

Rescue Intracranial Balloon Angioplasty with or without Stent Placement in Acute Strokes with Intracranial Atherosclerotic Disease.

BACKGROUND: Optimal management of acute ischemic stroke (AIS) secondary to intracranial atherosclerotic disease (ICAD) refractory to conventional mechanical thrombectomy remains unclear. We aimed to investigate the clinical outcome of patients undergoing rescue intracranial balloon angioplasty with or without stent placement in the setting of AIS in our institution. METHODS: This is a retrospective single-arm observational study to evaluate the efficacy and safety of rescue balloon angioplasty with or without stent placement in emergent large vessel occlusion (EVLO) strokes with underlying ICAD. We included all patients undergoing such rescue intervention within 24 hours of AIS presentation with EVLO between 2017 and 2021. We further evaluated stent or vessel reocclusion. RESULTS: Of 20 patients undergoing rescue intervention, 3 cases achieved adequate recanalization of artery using balloon angioplasty alone. Seventeen patients required stent placement. Fourteen (70%) procedures resulted in National Institutes of Health Stroke Scale improvement in postprocedure and upon discharge. Among 6 (30%) procedures with worsening neurological measures, 3 had reoccluded stent 24-48 hours after procedure, 2 had symptomatic hemorrhagic conversion, and 1 had perforator occlusion. Nine patients (45%) had favorable functional outcome (modified Rankin Scale ≤2) at discharge, unchanged or improved at 3-month follow-up. The median modified Rankin Scale score was 4 (Interquartile range: 1.75-4) at discharge, improving to 3 (Interquartile range: 0-4) at 3-month follow-up. Two patients (10%) died during hospital stay. CONCLUSIONS: Rescue angioplasty with or without stenting can lead to significant clinical improvement in patients with ICAD presenting with ELVO and refractory to thrombectomy; however, this procedure is associated with a high rate of morbidity in acute setting.

ADAMTS4 is involved in the production of the Alzheimer disease amyloid biomarker APP669-711.

Amyloid-ß (Aß) deposition in the brain parenchyma is one of the pathological hallmarks of Alzheimer disease (AD). We have previously identified amyloid precursor protein (APP)669-711 (a.k.a. Aß(-3)-40) in human plasma using immunoprecipitation combined with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (IP-MALDI-MS). Furthermore, we found that the level of a composite biomarker, i.e., a combination of APP669-711/Aß1-42 ratio and Aß1-40/Aß1-42 ratio in human plasma, correlates with the amyloid PET status of AD patients. However, the production mechanism of APP669-711 has remained unclear. Using in vitro and in vivo assays, we identified A Disintegrin and Metalloproteinase with a Thrombospondin type 1 motif, type 4 (ADAMTS4) as a responsible enzyme for APP669-711 production. ADAMTS4 cleaves APP directly to generate the C-terminal stub c102, which is subsequently proteolyzed by γ-secretase to release APP669-711. Genetic knockout of ADAMTS4 reduced the production of endogenous APP669-711 by 30% to 40% in cultured cells as well as mouse plasma, irrespectively of Aß levels. Finally, we found that the endogenous murine APP669-711/Aß1-42 ratio was increased in aged AD model mice, which shows Aß deposition as observed in human patients. These data suggest that ADAMTS4 is involved in the production of APP669-711, and a plasma biomarker determined by IP-MALDI-MS can be used to estimate the level of Aß deposition in the brain of mouse models.

An infantile traumatic brain injury with a bright tree appearance detected before the late seizure.

INDRODUCTION: Infantile traumatic brain injury (TBI) rarely follows a biphasic clinical course and exhibits a bright tree appearance (BTA) on magnetic resonance imaging (MRI). This is termed infantile traumatic brain injury with a biphasic clinical course and late reduced diffusion (TBIRD). TBIRD has clinical features similar to those of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). It remains to be clarified which patients with infantile TBI will develop TBIRD and the prevention and treatment of TBIRD. CASE AND REVIEW: We report a case of TBIRD that exhibited BTA 1 day before the late seizure and review 12 cases of TBIRD. All patients developed a subdural hematoma (SDH), were younger than 2 years, and presented with a biphasic phase within 3-6 days. The median interval between BTA and TBI was 5 days. Of the 5 cases examined with MRI before the biphasic phase, only our case was detected with BTA 4 days after TBI. CONCLUSION: Predicting the biphasic clinical course may be possible by examining MRI after TBI in patients under 2 years of age who develop SDH with unconsciousness, seizure, or hemiplegia, and these patients should be strictly followed up for 1 week.