Mutsumi Nagai

Vaccination with MCP-1 cDNA transfectant on human malignant glioma in nude mice induces migration of monocytes and NK cells to the tumor

Recently, studies on vaccination with tumor cells genetically engineered to produce monocyte chemoattractant protein-1 (MCP-1) have provided some encouragement. These studies have shown infiltration of certain types of lymphocytes at the tumor site. However, natural killer (NK) cells have not yet been assessed. We obtained a human malignant glioma cell line producing human MCP-1 constitutively by transfection of MCP-1 cDNA. We then test the effect of vaccination with the MCP-1 transfectant on nude mice. Although vaccination with MCP-1 transfectant did not reduce the tumor in our study, it was associated with the infiltration of large numbers of NK cells and monocytes at the tumor site. The site of vaccination also showed large numbers of monocytes. NK cells were detected with anti-asialo GM1 antibody, and monocytes were detected immunohistochemically with F4/80. We assumed that infiltrating monocytes at the site of vaccination could promote the infiltration of monocytes and NK cells into the tumor site without T-cell mediated transduction because the host lacked T-cell function.

A case of extravasation from a cerebral aneurysm during 3-dimensional computed tomography angiography.

BACKGROUND Reports of rebleeding from an aneurysm during 3D-CTA are rare because this imaging method is not widely available. In previous cases, rebleeding of the aneurysm presented with certain imaging features, which were cap-like, corkscrew-like, ribbon-like, and nebulous areas of enhancement. We had a patient whose aneurysm had reruptured during 3D-CTA. This is the sixth report. CASE DESCRIPTION The patient came to our hospital with SAH. A 3D-CTA showed a pooling of contrast medium in the temporal parenchyma and an aneurysm with an irregular bleb at the bifurcation of the right MCA. The aneurysm with bleb seemed to have a daughter aneurysm and a granddaughter aneurysm, which attached on the daughter aneurysm. We diagnosed rerupture during 3D-CTA because of a clear difference between the initial CT scan and those used as source data for 3D-CTA. Intraoperatively, we confirmed that a part of the aneurysm invaginated into the temporal lobe and that the possible granddaughter aneurysm was a clot on the daughter aneurysm. The intraparenchymal hematoma was attached to this clot. CONCLUSIONS We report a patient with rerupture of a cerebral aneurysm during 3D-CTA showing new pattern in the image. When extravasation of blood occurs into the brain parenchyma, 3D-CTA clearly demonstrates its extent because there is little attenuation by CSF. In such cases, extravasated blood can form both a small mass that mimics a granddaughter aneurysm and a pooling of contrast medium.

Ultrasonography monitoring with Superb Microvascular Imaging technique in brain tumor surgery.

BACKGROUND Neuronavigation based on preoperative magnetic resonance imaging has been developed as a useful tool to improve visibility of the surgical site in the operative field. Ultrasonography (US) monitoring has also been used as a reliable imaging technique, providing real-time information during neurosurgical operations. We combined the latest innovative imaging technique for detecting very low-flow components, Superb Microvascular Imaging (SMI), with US monitoring during brain tumor surgery. CASE DESCRIPTION Fifteen patients diagnosed with brain tumor (8 malignant and 7 benign) underwent neurosurgery with US monitoring using an Aplio 400/500 US system with the new SMI technique (imaging frequency, 10-12 MHz; frame rate, 28-31 Hz). Features of the SMI images in the gray scale mode include 1) visualization of low-velocity flow with minimal motion artifact, 2) high resolution of images, and 3) high frame rates. The tumors, tumor vessels, compressed and shifted healthy vessels, and cistern were clearly visualized on the SMI images in the gray scale mode, detailing the characteristics of healthy brain tissue (vertically penetrating, fine, straight vessels), glioblastoma (rounding, dilating, and bending vessels), low-grade glioma (fine and straight vessels), meningioma (many large and branching vessels), and lymphoma (less vascular, low echoic tumor) and demonstrating the tumor-defined border. We also performed biopsies under US monitoring with SMI. CONCLUSIONS We combined SMI technique with US monitoring during brain tumor surgery and observed healthy and tumor vessels. Further research is important for the development of a more precise and reliable neurosurgery.

An R132H Mutation in Isocitrate Dehydrogenase 1 Enhances p21 Expression and Inhibits Phosphorylation of Retinoblastoma Protein in Glioma Cells

Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain tumors loses its enzymatic activity for catalyzing isocitrate to α-ketoglutarate (α-KG) and acquires new activity whereby it converts α-KG to 2-hydroxyglutarate. The IDH1 mutation induces down-regulation of tricarboxylic acid cycle intermediates and up-regulation of lipid metabolism. Sterol regulatory element-binding proteins (SREBPs) regulate not only the synthesis of cholesterol and fatty acids but also acyclin-dependent kinase inhibitor p21 that halts the cell cycle at G1. Here we show that SREBPs were up-regulated in U87 human glioblastoma cells transfected with an IDH1R132H-expression plasmid. Small interfering ribonucleic acid (siRNA) for SREBP1 specifically decreased p21 messenger RNA (mRNA) levels independent of the p53 pathway. In IDH1R132H-expressing U87 cells, phosphorylation of Retinoblastoma (Rb) protein also decreased. We propose that metabolic changes induced by the IDH1 mutation enhance p21 expression via SREBP1 and inhibit phosphorylation of Rb, which slows progressionof the cell cycle and may be associated with non-aggressive features of gliomas with an IDH1 mutation.

Spontaneous Occlusion of the Frontal Arteriovenous Malformation and the Following Progression of the Associated Aneurysm: A Case Report

We report the case of a 59-year-old women with a cerebral arteriovenous malformation (AVM) in the right frontal lobe, which was detected incidentally. Additionally, an aneurysm was found at the feeding artery of the AVM. The patient was treated conservatively. Nine years later, the nidus of the AVM was no longer detectable. The angiography showed the associated aneurysm growing irregularly with a daughter sac. The spontaneous occlusion of an AVM and the following progression of an associated aneurysm are rare. The possible mechanisms leading to the occlusion of the AVM and the progression of the associated aneurysm are discussed.

Cochlear Nerve Action Potential Monitoring for Preserving Function of an Unseen Cochlear Nerve in Vestibular Schwannoma Surgery

BACKGROUND Intraoperative monitoring of cochlear nerve action potential (CNAP) has been used in patients with small vestibular schwannoma (<15 mm) to preserve cochlear nerve function. We performed surgery for a larger vestibular schwannoma under CNAP monitoring with the aim of preserving cochlear nerve function, and compared the data with findings from 10 patients with hemifacial spasm who underwent microvascular decompression surgery. CASE DESCRIPTION We report the case of a patient with a 26-mm vestibular schwannoma and normal hearing function who underwent neurosurgery under electrophysiological monitoring of the facial and cochlear nerves. Amplitudes of evoked facial muscle responses were maintained at approximately 70% during the operation. The latency of wave V on brainstem auditory evoked potential (BAEP) increased by 0.5 ms, and amplitude was maintained at approximately 70% of the value at the beginning of the operation. Latencies of P1, N1, and P2 on CNAP did not change intraoperatively. These latencies were comparable to those of 10 normal patients with hemifacial spasm. CNAP monitoring proved very useful in confirming the location of the cochlear nerve in the operative field and preserving cochlear nerve function. Both facial nerve function and hearing acuity were completely preserved after tumor removal, and wave V latency on BAEP returned to normal and was maintained in the normal range for at least 2 years. CONCLUSIONS CNAP monitoring is extremely useful for preserving the function of the unseen cochlear nerve during vestibular schwannoma surgery.

A Case of Atlantoaxial Dislocation surgically Fixated with Laminar Craw Hooks, Spinous Plates, and Occipital Plate System

Although cervical screw fixation is often demonstrated as biomechanical outstanding instrumentation for the case of upper cervical instability, only few reports have presented the complicated technique and high risk in the surgery. In this article, we show a case of atlantoaxial dislocation successfully fixated without any cervical screws.

Design of a Locator for Designing the Shortest Incision for a Polygonal Dural Window

When a wide polygonal dural window is created, a short dural incision length is preferred by surgeons because suturing a wastefully long incision line during closure is troublesome. A locator to facilitate making the shortest dural incision when creating a polygonal dural window would be helpful. We geometrically analyzed the shortest incision design for a pentagonal dural window and produced a simple locator for intraoperatively implementing this design. The design for a pentagonal dural window with the shortest incision is the same as the design for a minimum Steiner tree (MST) problem with five vertices. The MST consists of three interconnected Steiner points (SPs) with three equal, radiating branches. We produced a template of the features of the MST for a polygon (MST template) as a locator. The MST template consists of several uniform Steiner units (SUs), each of which has an SP at the center and three wings that branch off of the SP, and each SU also has three slits through which the wings of another unit can pass. This mechanism allows us to freely adjust the distance between the SPs of separate SUs. In clinical practice, we can create the shortest incision design for a quadrilateral or pentagon by arranging MST templates combining two or three SUs. If we open a wide dural window, the total incision lengths created using our method are 1–5 cm shorter than conventional incisions. The MST template accurately and easily reveals the shortest incision design.

Improvement of neurovascular function and cognitive impairment after STA-MCA anastomosis

OBJECTIVE In patients with severe steno-occlusive disease of a main cerebral artery, decreased cerebrovascular reserve (CVR) and cognitive impairment without causative focal lesions on magnetic resonance imaging have been reported. We examined ipsilateral and contralateral CVR and cognition before and after superficial temporal artery-middle cerebral artery (MCA) anastomosis operation in patients with internal carotid artery (ICA) or MCA occlusion. METHODS In 30 patients with ICA or MCA occlusion, cognitive impairment, and decreased CVR, we examined cognition, CVR, leukoaraiosis grades, and blood data. Data from 15 patients who underwent anastomosis were compared to that in 15 patients who did not undergo anastomosis, and to bilateral data already reported on 65 patients with severe steno-occlusive disease. RESULTS Cerebral blood flow, CVR, and cognition improved after anastomosis compared to before, and compared to patients without anastomosis; improved values were maintained for 5years. CVR recovered after anastomosis, matching the linear relationship between ipsilateral and contralateral CVR seen in the 65 patients. CONCLUSION The postoperative improvement in cognition and synchronized recovery on the regression line between CVR of the ipsilateral occlusion and contralateral sides may suggest that the CVR is widespread and nonselectively related to cognitive function.

Ultrasound-Guided Fine-Needle Aspiration in the Neck Region Using an Optical See-Through Head-Mounted Display: A Randomized Controlled Trial

The purpose of this study was to examine the feasibility of an optical see‐through head‐mounted display (OST‐HMD) to improve ergonomics during ultrasound‐guided fine‐needle aspiration (FNA) in the neck region.