[Intraoperative Fluorescence Imaging of Brain Tumors].

Malignant gliomas are highly invasive tumors. Accurate identification of tumor tissue is essential for enabling tumor resection as much as possible without damaging important neurological functions. One of the methods is intraoperative fluorescence imaging. This method visualizes in real time the boundary between the tumor and normal brain, which cannot be identified using conventional surgical microscope under white light. Although many fluorescent dyes have been reported for intraoperative fluorescence imaging of brain tumors, only 5-aminolevulinic acid(5-ALA)is approved by Ministry of Health, Labour and Welfare in Japan. After the oral administration of 5-ALA, fluorescence is emitted by protoporphyrin Ⅸ, a metabolite of 5-ALA in tumor cells(red fluorescence with a peak at 635 nm, induced by an excitation light of 405 nm). The intensity of fluorescence is correlated with tumor cell density, proliferation rate, and vascular density. In a multicenter randomized controlled study in Germany, compared with white light imaging, fluorescence imaging with 5-ALA increased the tumor resection rate and significantly prolonged progression-free survival at 6 months. However, no difference was observed in overall survival. Regarding other fluorescent substances, fluorescein sodium is a dye that leaks from tumor vessels without the blood-brain barrier, like contrast media used for computed tomography and magnetic resonance imaging(green fluorescence with a peak at 520 nm, induced by an excitation light of 493 nm). This dye spreads in the interstitial tissue of the tumor to visualize the tumor area. Indocyanine green emits a near-infrared light of 820-920 nm, induced by an excitation light of 760- 810 nm. This dye was expected to be useful for visualizing deep tumors as it emits light with high tissue permeability; however, it does not leak out of blood vessels because of its large molecular weight. Subsequently, this dye is used for intraoperative angiography of highly vascularized tumors. Talaporfin sodium was originally developed for photodynamic therapy in Japan and is readily taken up by tumor cells. This substance is also used for intraoperative fluorescence imaging because it emits the fluorescence of 672 nm, induced by an excitation light of 664 nm. Here, we review various fluorescent dyes used for intraoperative imaging of brain tumors.

PD-L1 and PD-L2 expression in the tumor microenvironment including peritumoral tissue in primary central nervous system lymphoma.

BACKGROUND: The prevalence of programmed death-ligand 1 (PD-L1) and PD-L2 expression on tumor cells and tumor-infiltrating immune cells in primary central nervous system lymphoma (PCNSL) remains unclear. In the present study, we analyzed needle biopsy and craniotomy specimens of patients with PCNSL to compare the PD-L1 and PD-L2 levels in the tumor and surrounding (peritumoral) tissue. We also assessed the correlation between biological factors and the prognostic significance of PD-L1 and PD-L2 expression. METHODS: We retrospectively analyzed the cases of 70 patients histologically diagnosed with PCNSL (diffuse large B-cell lymphoma). Immunohistochemistry for CD20, CD68, PD-L1, and PD-L2 was performed. In cases with specimens taken by craniotomy, the percentages of PD-L1- and PD-L2-positive macrophages were evaluated in both tumor and peritumoral tissue. The Kaplan-Meier method with log-rank test and Cox proportional hazard model were used for survival analysis. RESULTS: The tumor cells expressed little or no PD-L1 and PD-L2, but macrophages expressed PD-L1 and PD-L2 in most of the patients. The median percentage of PD-L2-positive cells was significantly higher among peritumoral macrophages (32.5%; 95% CI: 0-94.6) than intratumoral macrophages (27.5%; 95% CI: 0-81.1, p = 0.0014). There was a significant correlation between the percentages of PD-L2-positive intratumoral macrophages and PD-L2-positive peritumoral macrophages (p = 0.0429), with very low coefficient correlation (ρ = 0.098535). PD-L1 expression on macrophages was significantly associated with biological factors (intratumoral macrophages: better KPS, p = 0.0008; better MSKCC score, p = 0.0103; peritumoral macrophages: low proportion of LDH elevation, p = 0.0064) and longer OS (for intratumoral macrophages: high PD-L1 = 60 months, 95% CI = 30-132.6; low PD-L1 = 24 months, 95% CI = 11-48; p = 0.032; for peritumoral macrophages: high PD-L1 = 60 months, 95% CI = 30.7-NR; low PD-L1 = 14 months, 95% CI = 3-26). PD-L1 expression on peritumoral macrophages was strongly predictive of a favorable outcome (HR = 0.30, 95% CI = 0.12-0.77, p = 0.0129). CONCLUSIONS: Macrophages in intratumoral and peritumoral tissue expressed PD-L1 and PD-L2 at a higher rate than tumor cells. PD-L1 expression, especially on peritumoral macrophages, seems to be an important prognostic factor in PCNSL. Future comprehensive analysis of checkpoint molecules in the tumor microenvironment, including the peritumoral tissue, is warranted.

Folate receptor-targeted novel boron compound for boron neutron capture therapy on F98 glioma-bearing rats.

Folic acid (FA) has high affinity for the folate receptor (FR), which is limited expressed in normal human tissues, but over-expressed in several tumor cells, including glioblastoma cells. In the present work, a novel pteroyl-closo-dodecaborate conjugate (PBC) was developed, in which the pteroyl group interacts with FR, and the efficacy of boron neutron capture therapy (BNCT) using PBC was investigated. Thus, in vitro and in vivo studies were performed using F98 rat glioma cells and F98 glioma-bearing rats. For the in vivo study, boronophenylalanine (BPA) was intravenously administered, while PBC was administered by convection-enhanced delivery (CED)-a method for direct local drug infusion into the brain of rats. Furthermore, a combination of PBC administered by CED and BPA administered by intravenous (i.v.) injection was also investigated. In the biodistribution experiment, PBC administration at 6 h after CED termination showed the highest cellular boron concentrations (64.6 ± 29.6 µg B/g). Median survival time (MST) of untreated controls was 23.0 days (range 21-24 days). MST of rats administered PBC (CED) followed by neutron irradiation was 31 days (range 26-36 days), which was similar to that of rats administered i.v. BPA (30 days; range 25-37 days). Moreover, the combination group [PBC (CED) and i.v. BPA] showed the longest MST (38 days; range 28-40 days). It is concluded that a significant MST increase was noted in the survival time of the combination group of PBC (CED) and i.v. BPA compared to that in the single-boron agent groups. These findings suggest that the combination use of PBC (CED) has additional effects.

[Tentorial Dural Arteriovenous Fistula with Bithalamic Lesions and Bilateral Basal Ganglia Hemorrhage:A Case Report].

OBJECTIVE: We report an unusual case of tentorial dural arteriovenous fistula(DAVF)with bithalamic lesions and bilateral intracranial hemorrhage. CASE PRESENTATION: A 73-year-old man presented with lethargy and progressive cognitive decline. Imaging demonstrated bithalamic edematous lesions and bilateral basal ganglia hemorrhage in the right putamen and left internal capsule. Angiography revealed tentorial DAVF fed by both the internal and external carotid arteries. A shunted pouch was present in the superior petrosal sinus, and retrograde reflux drainage was see in the deep venous system, including the basal vein, vein of Galen, and internal cerebral veins with congestion. Initially, transarterial embolization was palliatively performed, and subsequently, a microsurgery achieved obliteration of the tentorial DAVF. Postoperatively, the bilateral thalamic changes disappeared, although sequela of the intracranial hemorrhage persisted. CONCLUSION: Deep venous congestion due to tentorial DAVF induced unusual bithalamic lesions and bilateral basal ganglia hemorrhage. Tentorial DAVF was treated with combined endovascular and surgical operations. Tentorial AVF is an aggressive vascular disease, and prompt diagnosis and treatment are necessary.

[The Efficacy of the Emergent Shunt-Clamp System for Secondary Hydrocephalus Associated with Fourth Ventricle Outlet Obstruction Syndrome:A Report of Two Cases].

Endoscopic third ventriculostomy(ETV)is the first-line treatment for fourth ventricle outlet obstruction(FVOO)-associated hydrocephalus. However, because FVOO is difficult to diagnose in the acute stage, ventriculoperitoneal shunt(VPS)is also used. Herein, we report two cases of shunted FVOO resulting in overdrainage or slit ventricle syndrome(SVS)that were treated successfully with the shunt-clamp system. In addition, we discuss the efficacy of the shunt-clamp system for FVOO-associated hydrocephalus. CASE 1:A 79-year-old man complained of severe postural headaches. One year earlier, he underwent VPS for secondary hydrocephalus associated with hemorrhagic cerebellar infarction. CT revealed that the ventricle had become slit-like. Although the shunt valve adjusted the maximum pressure, his complaint and the ventricle shape did not improve. After the on-off valve was inserted in the shunt system and clamped, his symptoms were resolved and the ventricle size was normalized. CASE 2:A 21-year-old man who complained of drowsiness, diplopia, and severe intermittent retroocular pain was admitted to our hospital. One year earlier, he underwent VPS with the shunt-clamp system for a secondary hydrocephalus after surgery for medulloblastoma. CT on admission revealed ventricle dilatation;however, the shape of the ventricle became slit-like 3 days after admission. We made a diagnosis of SVS and planned ETV. Owing to the difficulty in approaching the lateral ventricle, the shunt system was clamped 8 hours before the operation. After confirming ventricle dilatation, ETV was successfully performed. After the operation, the symptoms were resolved, and magnetic resonance imaging confirmed that the ventricle size was normalized.

Continuous Blood Glucose Monitoring May Detect Carotid Occlusion Intolerance during Carotid Artery Stenting.

BACKGROUND: The frequency of the occurrence of adverse events associated with carotid artery stenting (CAS) is usually low, but serious adverse events such as cerebral hyperperfusion syndrome (CHS) may occur. Real-time monitoring is ideal for the early detection of adverse events during the surgical procedure. This study aimed to evaluate continuous blood glucose (BG) monitoring for the detection of adverse events during CAS. METHODS: Forty patients undergoing scheduled CAS were prospectively enrolled. An artificial pancreas was used for continuous BG monitoring (once per minute), using venous blood extracted at a rate of 2 mL/hr during CAS. The primary endpoint was a correlation between BG change and adverse events. RESULTS: CAS was discontinued in 1 patient, and BG was not measured in 5 patients (12.5%) because of the inability to extract blood. Among 34 evaluable patients, no patient developed CHS, but 3 patients (9%) experienced carotid occlusion intolerance. During CAS, BG was significantly higher in patients with carotid occlusion intolerance (median: 5 mg/dL) than in patients without carotid occlusion intolerance (median: 0 mg/dL) (P = 0.0221). A cutoff BG value ≥4 mg/dL during CAS showed 50% sensitivity and 100% specificity for the detection of carotid occlusion intolerance. There was no significant correlation between BG change and other adverse events. CONCLUSIONS: BG elevation may help detect carotid occlusion intolerance although it is still unknown whether BG monitoring can detect CHS. Further studies should validate that a cutoff BG elevation value of ≥4 mg/dL during CAS indicates carotid occlusion intolerance.

Efficacy and safety of non-suture dural closure using a novel dural substitute consisting of polyglycolic acid felt and fibrin glue to prevent cerebrospinal fluid leakage-A non-controlled, open-label, multicenter clinical trial.

The objective of this study is to evaluate the efficacy and safety of non-suture dural closure using a novel dural substitute (GM111) consisting of polyglycolic acid felt with a fibrin-glue-coated area commensurate in size with the dural defect. This was a non-controlled, open-label, multicenter clinical trial. The efficacy evaluation endpoints were (1) GM111's intra-operative capability to close dural defects and (2) prevention of cerebrospinal fluid (CSF) leakage and subcutaneous CSF retention throughout the postoperative period (evaluated by diagnostic imaging). Patients meeting the following three preoperative and two intra-operative selection criteria were enrolled: (1) between 12 and <75 years of age; (2) the dura is surmised to be defective and in need of reconstruction; (3) informed written consent was obtained from the patient; (4) the surgical wound is class 1; and (5) the size of duraplasty is ≥0.2 cm2 to <100 cm2. Sixty patients were enrolled. The craniotomy site was supratentorial in 77.2%, infratentorial in 12.3% and sellar in 10.5%. The GM111 prosthesis size ranged from 0.24 to 42 cm2. To evaluate the efficacy, intra-operative closure was confirmed by Valsalva's maneuver, water infusion, etc., in all patients. CSF leakage and subcutaneous CSF retention throughout the postoperative period were found in four patients. Adverse events for which a causal relationship with GM111 could not be ruled out occurred in 8.8% of the patients. There were no instances of postoperative infection due to GM111. GM111 showed good closure capability and safety when used for non-suture dural closure.

Long-term therapeutic effects of vertebroplasty for painful vertebral compression fracture: a retrospective comparative study.

As a treatment for painful vertebral compression fractures (VCFs), vertebral perforation does not require bone cement infusion. Here, we retrospectively assessed the long-term therapeutic effects of vertebroplasty in a comparison with those of vertebral perforation. The subjects were 64 patients who underwent percutaneous vertebroplasty (PVP group) and 67 patients who underwent vertebral perforation (Perforation group) between 2006 and 2011 at Takeda general hospital. We compared the analgesic effects of the treatments and the incidences of new VCFs between the groups at 15 months postsurgery. The pain scores on a visual analog scale 15 months postsurgery were 2.3 ± 2.0 in the PVP group and 2.1 ± 1.4 in the Perforation group, a nonsignificant difference (p = .90). The presence of vertebral mobility did not influence the analgesic effect in either group. New VCFs developed at a significantly higher rate in the PVP group (n = 27, 52%) compared to the Perforation group (n = 11, 24%; p = .0017). This difference was even greater within 3 months of the surgery, in 19 PVP patients (38%) and two Perforation patients (3.0%; p < .0001). However, the incidence after 3 months was eight PVP patients and nine Perforation patients, a nonsignificant difference (p = .50). The Kaplan-Meier analysis suggested that the new fractures after surgery in both treatment groups may occur at the same frequency at around 31 months postoperatively. Vertebroplasty is more effective than vertebral perforation in relieving pain early in the course of treatment, but over the long term, no significant difference in pain was seen between the two treatments. The complication of new fractures seen with cement vertebroplasty is only seen after the procedure.

Innovations in Endovascular Treatment Strategies for Large Carotid Cavernous Aneurysms-The Safety and Efficacy of a Flow Diverter.

BACKGROUND: The efficacy for the treatment of large carotid cavernous aneurysms (CCAs) was compared between conventional endovascular treatments, stent-assisted coiling (SAC), parent artery occlusion (PAO), and the flow diverter (FD). METHODS: Between January 2001 and December 2015, 49 patients with large, broad-necked, unruptured CCA underwent endovascular treatment at our institution. We performed PAO in 22 patients, SAC in 18 patients, and FD in 9 patients. Safety and efficacy were assessed in all patients by periodic clinical and radiological examinations during a 6-month follow-up. RESULTS: All 22 aneurysms treated with PAO disappeared immediately after treatment, but in the SAC-treated group, complete occlusion was obtained in only 5 of the 18 patients. All aneurysms in the FD group resulted in body filling. Perioperative ipsilateral temporary ischemic events occurred in 6 cases (PAO 4, SAC 2, FD 0). Delayed deterioration or new onset of cranial nerve symptoms was observed in 10 cases (PAO 3, SAC 3, FD 4), almost all of which recovered within 3 months. During the 6-month follow-up, all aneurysms treated with PAO showed a decrease in size without recanalization. In the SAC group, 12 aneurysms showed neck remnants, and marked recanalization occurred in 4 cases. Six of the 9 aneurysms in the FD group were completely occluded. CONCLUSIONS: The FD provided excellent final results despite transient worsening of symptoms. Although further long-term follow-up is essential, from a cost-effective and time-saving viewpoint, FD is a relatively safe and reliable method for the treatment of large CCAs.

Transthyretin Concentrations in Acute Stroke Patients Predict Convalescent Rehabilitation.

OBJECTIVE: For stroke patients, intensive nutritional management is an important and effective component of inpatient rehabilitation. Accordingly, acute care hospitals must detect and prevent malnutrition at an early stage. Blood transthyretin levels are widely used as a nutritional monitoring index in critically ill patients. Here, we had analyzed the relationship between the transthyretin levels during the acute phase and Functional Independence Measure in stroke patients undergoing convalescent rehabilitation. METHODS: We investigated 117 patients who were admitted to our hospital with acute ischemic or hemorrhagic stroke from February 2013 to October 2015 and subsequently transferred to convalescent hospitals after receiving acute treatment. Transthyretin concentrations were evaluated at 3 time points as follows: at admission, and 5 and 10 days after admission. After categorizing patients into 3 groups according to the minimum transthyretin level, we analyzed the association between transthyretin and Functional Independence Measure. RESULTS: In our patients, transthyretin levels decreased during the first 5 days after admission and recovered slightly during the subsequent 5 days. Notably, Functional Independence Measure efficiency was significantly associated with the decrease in transthyretin levels during the 5 days after admission. Patients with lower transthyretin levels had poorer Functional Independence Measure outcomes and tended not to be discharged to their own homes. DISCUSSION: A minimal transthyretin concentration (<10 mg/dL) is predictive of a poor outcome in stroke patients undergoing convalescent rehabilitation. In particular, an early decrease in transthyretin levels suggests restricted rehabilitation efficiency. Accordingly, transthyretin levels should be monitored in acute stroke patients to indicate mid-term rehabilitation prospects.

Successful recanalization for internal carotid artery occlusion with persistent primitive trigeminal artery manifesting only as ischemia of the posterior circulation.

BACKGROUND: Internal carotid artery (ICA) occlusion mainly manifests as ischemia of the anterior circulation. There are very few reports of ICA occlusion manifesting as only ischemia of the posterior circulation related to a fetal type posterior communicating artery or other arteries. CASE PRESENTATION: The authors experienced a case of ICA occlusion with persistent primitive trigeminal artery (PPTA) manifesting only as ischemia of the posterior circulation. In this case, the initial NIHSS score was high (35/42 points). Additionally, cross flow of the anterior communicating artery, ICA occlusion and basilar artery (BA) occlusion were represented on the initial head MRA. Therefore, our first impression was a presumptive diagnosis of BA occlusion. Prior head MRI/MRA performed for screening purposes, had incidentally demonstrated a right PPTA. Based on this understanding, we were able to determine the exact angioarchitectural mechanism of the ICA occlusion. Because of the presence of the PPTA, successful recanalization was accomplished expeditiously. CONCLUSION: Although the presence of PPTA is rare and ICA occlusion patients with PPTA is even more unusual, if ICA occlusion and BA occlusion appear simultaneously on MRA, the presence of PPTA should be considered.

Spinopelvic alignment and sagittal balance of asymptomatic adults with 6 lumbar vertebrae.

PURPOSE: The purpose of this study was to evaluate total spinal alignment in asymptomatic individuals with 6 lumbar vertebrae (LVs). METHODS: The present study comprised 167 Japanese adult volunteers with no spinal symptoms. In all individuals, standing radiographs of the entire spine were taken to measure the pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), C7 sagittal vertical axis (C7SVA), T1 slope, thoracic kyphosis (TK), C2-C7 sagittal vertical axis (C2-C7 SVA), and C2-C7 lordosis (C2-C7L). We used these parameters to compare individuals with 5LVs to those with 6LVs. We performed additional investigations regarding the relationship between L6 morphological characteristics and parameters. RESULTS: Out of 167 individuals, 6LVs were present in 29 (17.4 %). PI was significantly greater in individuals with 6LVs (64.8° ± 9.54°) than in those with 5LVs (51.3° ± 10.1°, P < 0.0001). Individuals with 6LVs also had significantly larger SS, PT, and C7SVA values (SS: P = 0.0125, PT: P < 0.0001, C7SVA: P = 0.0172). LL tended to be nonsignificantly greater in individuals with 6LVs (P = 0.1588). All of these changes were more noticeable in individuals in whom the L6 vertebra was classified as type II and III according to the Castellvi classification. Meanwhile, the presence of 6LVs has little influence on the alignment of the superior lumber vertebrae. CONCLUSIONS: Asymptomatic individuals with 6LVs presented with different spinopelvic alignment compared to those with 5LVs. We need to establish a treatment strategy for symptomatic 6LV cases.

Analysis of Small Ischemic Lesions in the Examinees of a Brain Dock and Neurological Examination of Animals Subjected to Cortical or Basal Ganglia Photothrombotic Infarction.

We analyzed cases of small brain ischemic lesions found in examinees of a brain dock (neurological health screening center). Small cerebral infarction was found in 17 % of the examinees (733 cases). White matter lesions were found in 24 %. Infarctions were located in the cortex or subcortical white matter in 31 % and in the basal ganglia in 44 % of cases. Infratentorial infarction was found in 1.6 %. We have developed an animal model of small infarction in the cortex or basal ganglia induced by photothrombosis in rodents. Sprague-Dawley rats or Mongolian gerbils were anesthetized and photothrombotic infarction was induced in the left caudate nucleus or parietal cortex by light exposure via an optic fiber and intravenous Rose Bengal dye injection. Histological examination revealed development of a small spherical infarction surrounding the tip of the optic fiber. The lesion turned to a cyst by 6 weeks after lesioning. Neurological deficits were found in animals both with cortical and caudate infarction. Behavioral changes in an open field test differed with the lesion site. Neurological deficits were sustained longer in animals with larger infarctions. Thus, photothrombotic infarction is useful for analyzing location-dependent and size-dependent neurological and neuropathological changes after cerebral infarction.

[A Case of Subacute Combined Degeneration Caused by Vitamin B12 Deficiency in a Cervical Spondylosis Surgery Referral].

A 62-year-old man with a 1-year history of numbness of the extremities, clumsiness, and gait disorder was diagnosed with cervical spondylotic myelopathy at a neighboring clinic and referred to our institution for surgery. The patient had undergone a total gastrectomy 6 years previously. Flattening of the cervical cord, associated with diffuse cervical spondylosis and intramedullary intensity change, was observed on magnetic resonance imaging of the cervical spine. Neurological examination revealed decreased vibratory and position sense in all limbs, with posterior funiculus-based neurological symptoms. Blood biochemistry revealed decreased vitamin B12(VB12)levels and megaloblastic anemia. On the basis of these findings, the patient was diagnosed with subacute combined degeneration(SCD). The patient was treated with VB12 for 3 months; the gait disorder resolved and the intramedullary intensity changes in the posterior column of the medulla oblongata, thoracicus, and spinal cord were no longer observed. SCD is a pathological condition in which recovery of neurological function may be achieved through early administration of VB12. In some cases, it is difficult to differentiate between this condition and cervical spondylotic myelopathy because both diseases exhibit progressive spinal symptoms. The medical history and results of neurological evaluations of the patient are important for an accurate diagnosis, and should therefore not be overlooked.

Postoperative change in sagittal balance after Kyphoplasty for the treatment of osteoporotic vertebral compression fracture.

PURPOSE: The influence of vertebral cement augmentation on spinal sagittal balance is unknown. The present study aimed to analyze the changes in total spinal alignment after Kyphoplasty in VCF patients. METHODS: The study involved 21 VCF patients who underwent Kyphoplasty. In all patients, lateral radiographs of the entire spine were taken preoperatively and 1 month after surgery, to measure the pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), sagittal vertical axis (SVA), and spinosacral angle (SSA). These parameters were compared between VCF patients and 30 healthy volunteers. In VCF patients, the parameters were compared before and after Kyphoplasty. RESULTS: In VCF patients, preoperative SVA was 7.00 ± 3.9 cm, showing a significant shift to anterior sagittal balance as compared to the healthy group (1.45 ± 2.7 cm) (P < 0.0001). Preoperative SS was smaller and PT was larger in VCF group than in the healthy group (P < 0.05). After Kyphoplasty, SVA decreased to 5.02 ± 2.91 (P = 0.0007) and LL and SSA increased (LL P = 0.028; SSA P = 0.0031). Postoperative decrease of SVA was correlated with the kyphotic change of treated vertebra (r = 0.792, P < 0.01). VAS score decreased from 7.98 ± 1.8 before Kyphoplasty to 2.38 ± 2.3 postoperatively (P < 0.0001). CONCLUSIONS: Total spinal alignment is shifted to anterior sagittal balance in VCF patients. Kyphoplasty plays a role not only in reducing pain associated with fractures but also in improving sagittal imbalance in the treatment of painful vertebral compression fracture.

Delayed brain radiation necrosis: pathological review and new molecular targets for treatment.

Delayed radiation necrosis is a well-known adverse event following radiotherapy for brain diseases and has been studied since the 1930s. The primary pathogenesis is thought to be the direct damage to endothelial and glial cells, particularly oligodendrocytes, which causes vascular hyalinization and demyelination. This primary pathology leads to tissue inflammation and ischemia, inducing various tissue protective responses including angiogenesis. Macrophages and lymphocytes then infiltrate the surrounding areas of necrosis, releasing inflammatory cytokines such as interleukin (IL)-1α, IL-6, and tumor necrosis factor (TNF)-α. Microglia also express these inflammatory cytokines. Reactive astrocytes play an important role in angiogenesis, expressing vascular endothelial growth factor (VEGF). Some chemokine networks, like the CXCL12/CXCR4 axis, are upregulated by tissue inflammation. Hypoxia may mediate the cell-cell interactions among reactive astrocytes, macrophages, and microglial cells around the necrotic core. Recently, bevacizumab, an anti-VEGF antibody, has demonstrated promising results as an alternative treatment for radiation necrosis. The importance of VEGF in the pathophysiology of brain radiation necrosis is being recognized. The discovery of new molecular targets could facilitate novel treatments for radiation necrosis. This literature review will focus on recent work characterizing delayed radiation necrosis in the brain.

[Significance of susceptibility-weighted angiography for endovascular thrombectomy of acute ischemic stroke].

Efficacy of intravenous systemic thrombolysis is limited in patients with large-vessel occlusion and for whom more than 4.5 hours have passed since onset. As such, mechanical thrombectomy has been the mainstay therapy for these patients. Localization of the intra-arterial clot prior to thrombectomy can be beneficial in cases of acute ischemic stroke. Here, we present 3 cases of acute ischemic stroke that were initially imaged with susceptibility-weighted angiography(SWAN)before endovascular thrombectomy(middle cerebral artery occlusion, internal carotid artery occlusion, basilar artery occlusion)was attempted. In all 3 cases, clot localization by SWAN was consistent with that by angiography, and recanalization was successful. Identifying clot location and composition may help determine the optimal treatment and predict successful recanalization.

Bevacizumab treatment for symptomatic radiation necrosis diagnosed by amino acid PET.

Bevacizumab is effective in treating radiation necrosis; however, radiation necrosis was not definitively diagnosed in most previous reports. Here we used amino acid positron emission tomography to diagnose radiation necrosis for the application of bevacizumab in treating progressive radiation necrosis. Lesion/normal tissue ratios of <2.5 on (18)fluoride-labeled boronophenylalanine-positron emission tomography were defined as an indication of effective bevacizumab treatment. Thirteen patients were treated with bevacizumab at a dose of 5 mg/kg every 2 weeks. Two patients were excluded because of adverse events. The median reduction rate in perilesional edema was 65.5%. Karnofsky performance status improved in six patients after bevacizumab treatment. Lesion/normal tissue ratios on (18)fluoride-labeled boronophenylalanine-positron emission tomography (P = 0.0084) and improvement in Karnofsky performance status after bevacizumab treatment (P = 0.0228) were significantly associated with reduced rates of perilesional edema. Thus, (18)fluoride-labeled boronophenylalanine-positron emission tomography could be useful for diagnosing radiation necrosis and predicting the efficacy of bevacizumab in progressive radiation necrosis.

International brain edema symposia 1967-2011.

This is a brief review of previous international brain edema symposia. The symposia that took place from 1965 to 1999 were summarized by Igor Klatzo and A. Marmarou in the proceedings Brain Edema XI [1]. In this article the author summarized the symposia, including latest five. Images from previous symposia such as the cover pages of the proceedings and snapshots of organizers were included. The outline and key words of the symposia were summarized in tables. The name of the prize winner and the title of the memorial lectures in recent symposia were also summarized in a table.

Brain edema and blood-brain barrier opening after photothrombotic ischemia in rat.

We have examined the time course of brain edema and the blood-brain barrier opening in rat after basal ganglia ischemia induced by photothrombotic occlusion of the small vessels within the caudate-putamen. Male SD rats were anesthetized, and Rose Bengal dye was intravenously injected. The left caudo-putamen was exposed to cold white light for 5-10 min via a stereotaxically implanted optic fiber. Ischemic brain edema and the blood-brain barrier, as well as the histological changes, were assessed at various times during the following 6 weeks. Local cerebral blood flow was measured 90 min after photothrombosis by quantitative autoradiography. A round infarct with thrombosed parenchymal vessels surrounded by a layer of selective neuronal death was formed within the caudo-putamen. The ischemic lesion turned into a lacune over a period of 6 weeks. A central zone of markedly reduced blood flow and a surrounding oligemic zone were observed 90 min after light exposure. Early blood-brain barrier opening with edema was observed as early as 4 h after photothrombosis, peaked at day 1, and disappeared at 7 days after photothrombosis. In a model of lacunar infarction, we observed an early and transient brain edema and blood-brain opening after onset of ischemia.