Border Zone Maybe Correlated with Radiation Necrosis After Radiosurgery in Metastatic Brain Tumor.

BACKGROUND: Radiation necrosis (RN) after stereotactic radiosurgery (SRS) in brain metastases has been extensively evaluated, and RN is correlated with various risk factors. However, no study comprehensively analyzed the correlation between RN and the border zones of the brain that are vulnerable to ischemia. We hypothesized that patients with tumors in the border zone are at high risk of RN. Hence, the current study aimed to assess the correlation between border zone lesions and RN, with consideration of other predetermined factors. METHODS: This retrospective study included 117 patients with 290 lesions who underwent Gamma Knife SRS. Radiological and clinical analyses were performed to identify factors possibly correlated with RN. Notably, the lesion location was classified into 2 groups (border zone and nonborder zone) based on the blood supply. RESULTS: In total, 22 (18.8%) patients with 22 (7.5%) lesions developed RN. Univariate analysis revealed a significant correlation between RN and external border zone lesions, second course of SRS administered at the same site of the previous SRS, prescribed dose, and tumor volume. Multivariate analysis showed that border zone lesions, second course of SRS at the same site of the previous SRS, and tumor volume were significantly correlated with RN. CONCLUSIONS: Patients with tumors in the border zone are at high risk of RN. The potential risks of RN can be attributed hypothetically to hypoperfusion. Hence, the association between RN and border zone lesions seems reasonable.

Inhibition of Glial Activation and Subsequent Reduction in White Matter Damage through Supplementation with a Combined Extract of Wheat Bran, Citrus Peel, and Jujube in a Rat Model of Vascular Dementia.

Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease. In our previous studies, we showed that wheat bran extract (WBE) reduced white matter damage in a rat VaD model and improved memory in a human clinical trial. However, starch gelatinization made the large-scale preparation of WBE difficult. To simplify the manufacturing process and increase efficacy, we attempted to find a decoction containing an optimum ratio of wheat bran, sliced citrus peel, and sliced jujube (WCJ). To find an optimal ratio, the cell survival of C6 (rat glioma) cultured under hypoxic conditions (1% O2) was measured, and apoptosis was assessed. To confirm the efficacies of the optimized WCJ for VaD, pupillary light reflex, white matter damage, and the activation of astrocytes and microglia were assessed in a rat model of bilateral common carotid artery occlusion (BCCAO) causing chronic hypoperfusion. Using a combination of both searching the literature and cell survival experiments, we chose 6:2:1 as the optimal ratio of wheat bran to sliced citrus peel to sliced jujube to prepare WCJ. We showed that phytic acid contained only in wheat bran can be used as an indicator component for the quality control of WCJ. We observed in vitro that the WCJ treatment improved cell survival by reducing apoptosis through an increase in the Bcl-2/Bax ratio. In the BCCAO experiments, the WCJ-supplemented diet prevented astrocytic and microglial activation, mitigated myelin damage in the corpus callosum and optic tract, and, consequently, improved pupillary light reflex at dosages over 100 mg/kg/day. The results suggest that the consumption of WCJ can prevent VaD by reducing white matter damage, and WCJ can be developed as a safe, herbal medicine to prevent VaD.

Venous ectasia preceding intra-tumoral hemorrhage in a case of gliosarcoma with transverse sinus involvement.

Although intratumoral hemorrhage is common in patients with malignant brain tumors, reports on its clinical course are scarce. This report presents a rare case of a patient with intratumoral hemorrhage with gliosarcoma invading the venus sinus. This invasion and a small draining vein were observed at diagnosis. Magnetic resonance imaging performed 1 week later showed new-onset venous ectasia, which caused intratumoral hemorrhage. This case provides insight into the mechanisms underlying intratumoral hemorrhage and highlights the emergence of new intratumoral vasculature as a potential warning sign for hemorrhage.

Novel Animal Model of Spontaneous Cerebral Petechial Hemorrhage Using Focused Ultrasound in Rats.

Background and Objectives: Petechial cerebral hemorrhages can be caused by various factors, such as traumas, cerebral infarctions, and aging, and is related to the disruption of the blood-brain barrier or the cellular damage of blood vessels. However, there is no animal model that recapitulates cerebral petechial hemorrhages. Materials and Methods: Here, we implemented a petechial hemorrhage using a novel technology, i.e., microbubble-assisted focused ultrasound (MB + FUS). Results: This method increases the permeability of the blood-brain barrier by directly applying mechanical force to the vascular endothelial cells through cavitation of the microbubbles. Microbubble-enhanced cavitation has the advantage of controlling the degree and location of petechial hemorrhages. Conclusions: We thus generated a preclinical rat model using noninvasive focal MB + FUS. This method is histologically similar to actual petechial hemorrhages of the brain and allows the achievement of a physiologically resembling petechial hemorrhage. In the future, this method shall be considered as a useful animal model for studying the pathophysiology and treatment of petechial cerebral hemorrhages.

Effect of Cadherin-11 Expression on the Prognosis of a Newly Diagnosed Primary Glioblastoma.

BACKGROUND: Cadherin-11, a cell-to-cell adhesion molecule, is associated with higher tumor grade and decreased patient survival. The purpose of this study was to investigate the clinical significance of cadherin-11 expression in the progression and prognosis of a newly diagnosed primary glioblastoma (GBL). METHODS: Between 2007 and 2016, 52 out of 178 patients diagnosed with a GBL and satisfied the following criteria: 1) a new primary GBL, 2) gross-total resection, 3) immunohistochemically-available tissue, and 4) standardized adjuvant treatment. RESULTS: In terms of staining intensity, the low-intensity cadherin-11 group showed longer progression-free survival (PFS) than the high-intensity cadherin-11 group (median PFS, 12.0 months [95% CI, 11.1-12.9] vs. median PFS, 6.0 months [95% CI, 3.7-8.3]; p<0.001). The low-intensity cadherin-11 group revealed longer overall survival (OS) than the high-intensity cadherin-11 group (median OS, 20.0 months [95% CI, 11.8-16.6] vs. median OS, 15.0 months [95% CI, 11.8-18.2]; p=0.003). The staining intensity of cadherin-11 was a statistically significant factor in PFS and OS in terms of univariate and multivariate analyses (univariate analysis: p<0.001 and p=0.005; multivariate analysis: p<0.001 and p=0.005). CONCLUSION: Our clinical study demonstrates high cadherin-11 expression may be associated with poor PFS and OS for a newly diagnosed primary GBL.

Clinical significance of vitamin D in idiopathic normal pressure hydrocephalus.

BACKGROUND: Although recent studies show vitamin D deficiency is associated with cognitive decline, urinary incontinence, and gait instability, there has been no study on the effect of vitamin D on idiopathic normal pressure hydrocephalus (iNPH) characterized by the classic symptom triad of cognitive decline, urinary incontinence, and gait instability. We investigated the clinical significance of vitamin D in patients with iNPH. METHODS: Between 2017 and 2020, 44 patients who underwent ventriculoperitoneal shunt surgery were divided into low (< 15 ng/mL) and high (≥ 15 ng/mL) vitamin D groups according to the concentration of 25(OH)D, an effective indicator of vitamin D status. They were respectively evaluated according to clinical and radiological findings. RESULTS: The low vitamin D group (n = 24) showed lower preoperative cognition compared to the high vitamin D group (n = 20) in terms of Korean-Mini Mental Status Examination (K-MMSE) and iNPH grading scale (iNPHGS) (K-MMSE: 20.5 ± 5.4 versus 24.0 ± 4.5, p = 0.041; iNPHGS cognitive score: 2 ± 0.9 versus 1 ± 0.6, p = 0.025). And the low vitamin D group showed pre- and postoperatively more severe urinary incontinence (preoperative iNPHGS urinary score: 1 ± 1.0 versus 0 ± 0.9, p = 0.012; postoperative iNPHGS urinary score:1 ± 1.0 versus 0 ± 0.9, p = 0.014). The score of narrow high-convexity sulci for the low vitamin D group was lower (low vitamin D group: 1 ± 0.7 versus high vitamin D group: 2 ± 0.4, p = 0.031). CONCLUSION: Lower concentration of vitamin D in iNPH may be related to lower preoperative cognition, pre- and postoperative urinary incontinence, and brain morphological change.

Neuromyelitis Optica Spectrum Disorders Mimicking Multiple Brain Tumors.

We report a rare case of neuromyelitis optica spectrum disorders (NMOSD), mimicking multiple brain tumors. A 53-year-old woman presented with weakness and paresthesia in her right arm and leg. Upon admission, brain MRI showed about 10 multiple brain tumors, which had to be differentiated from multiple brain metastases, lymphoma, and high-grade glioma in both hemispheres. No primary cancer was found in the chest-abdomen-pelvis CT. Subsequent spine MRI revealed multifocal cord signal change involving C2-T7, suggesting myelitis. A decrease in visual acuity was noted when taking a medical history, and optic neuritis was diagnosed upon ophthalmologic examination. With clinical and radiological appearances, multiple brain and spinal cord lesions have been diagnosed as NMOSD. Steroid and immunosuppressive drugs were administered. We should consider the possibility of an autoimmune disease, such as NMOSD, involving the optic nerve, spinal cord, and central nervous system when multiple hemispheric tumefactive lesions are observed.

Arrested Pneumatization of the Sphenoid Sinus in the Skull Base.

We report 2 cases of arrested pneumatization of the sphenoid sinus, a normal variant commonly misdiagnosed as a serious condition of the skull base. A 65-year-old man visited a local clinic for regular checkups. Brain CT showed a non-expansile lesion of the soft tissue with a well-defined sclerotic margin in the clivus but without destruction or mass effect on the surrounding bony structures. Subsequent brain MRI revealed that the lesion within the clivus was a high-signal lesion on the T2-weighted image, containing a low-signal round mass seen on a high-intensity signal on the T1-weighted image without contrast enhancement. Thus, the lesion was considered to contain internal fat. A 70-year-old woman diagnosed with a tumor in the greater sphenoid bone visited our hospital. Her brain CT revealed a non-expansile lesion of mixed density and a well-demarcated lesion and internal curvilinear calcification in the left greater wing of the sphenoid bone. The margin was osteosclerotic and the adjacent bony structure was intact. Her brain MRI showed that the lesion within the greater sphenoid bone had multiple low-signal lesions within a high-signal lesion on the T2-weighted image, suggesting internal fat contents. The lesions were diagnosed as arrested pneumatization of the sphenoid sinus and no further examination or treatment was performed. Arrested pneumatization of the sphenoid sinus should be considered in the presence of non-expansile lesion with an osteosclerotic boundary and internal fat component in the skull base.

Spindle cell oncocytoma of the sella turcica with anaplastic features and rapid progression in short-term follow-up: a case report with proposal of distinctive radiologic features.

We present a rare case of spindle cell oncocytoma (SCO) of the sella turcica with malignant histologic features and rapid progression. A 42-year-old woman experienced bilateral blurred vision and was preoperatively misdiagnosed as having a pituitary macroadenoma on magnetic resonance imaging. After surgery, SCO was diagnosed by the histopathologic features of interlacing fascicles of spindle tumor cells with finely granular, eosinophilic cytoplasm. Focal anaplastic changes and necrosis were present. Immunohistochemically, the tumor cells were positive for vimentin, epithelial membrane antigen, S-100, galectin-3, and thyroid transcription factor 1. Four months later, the tumor had progressed, and second surgery with adjuvant radiotherapy was performed; the patients remains under observation. In this report, we proposed distinctive radiologic features for differential diagnosis between SCO and other pituitary tumors.

Sinonasal Teratocarcinosarcoma, a Rare Tumor Involving Both the Nasal Cavity and the Cranial Cavity.

Sinonasal teratocarcinosarcoma (SNTCS), a very rare tumor, is known to be a heterogeneous with epithelial, mesenchymal, and neuroepithelial components and shows a very aggressive clinical course. Due to the heterogeneity of this tumor, it is often misdiagnosed. No definitive treatment modality has been reported because it is a very rare tumor. A 44-year-old man presented to a rhinologist with headache and nasal obstruction, and an intranasal tumor was found that invaded into the cranial cavity. He underwent combined surgery with a rhinologist and a neurosurgeon following cognitive decline that worsened after a transnasal biopsy. The patient was diagnosed with SNTCS and underwent radiotherapy. However, residual tumor was found during radiotherapy and additional chemotherapy was administered. Follow-up brain MRI revealed no remnant or recurrent lesion. SNTCS is a tumor that has not yet been well researched and should be further investigated for proper treatment.

Studies of combined NO-eluting/CD47-modified polyurethane surfaces for synergistic enhancement of biocompatibility.

The blood compatibility of various intravascular (IV) devices (e.g., catheters, sensors, etc.) is compromised by activation of platelets that can cause thrombus formation and device failure. Such devices also carry a high risk of microbial infection. Recently, nitric oxide (NO) releasing polymers/devices have been proposed to reduce these clinical problems. CD47, a ubiquitously expressed transmembrane protein with proven anti-inflammation/anti-platelet properties when immobilized on polymeric surfaces, is a good candidate to complement NO release in both effectiveness and longevity. In this work, we successfully appended CD47 peptides (pepCD47) to the surface of biomedical grade polyurethane (PU) copolymers. SIRPα binding and THP-1 cell attachment experiments strongly suggested that the pepCD47 retains its biological properties when bound to PU films. In spite of the potentially high reactivity of NO toward various amino acid residues in CD47, the efficacy of surface-immobilized pepCD47 to prevent inflammatory cell attachment was not inhibited after being subjected to a high flux of NO for three days, demonstrating excellent compatibility of the two species. We further constructed a CD47 surface immobilized silicone tubing filled with NO releasing S-nitrosoglutathione/ascorbic acid (GSNO/AA) solution for synergistic biocompatibility evaluation. Via an ex vivo Chandler loop model, we demonstrate for the first time that NO release and CD47 modification could function synergistically at the blood/material interface and produce greatly enhanced anti-inflammatory/anti-platelet effects. This concept should be readily implementable to create a new generation of thromboresistant/antimicrobial implantable devices.

Chronic Hyperglycemia before Spinal Cord Injury Increases Inflammatory Reaction and Astrogliosis after Injury: Human and Rat Studies.

Traumatic spinal cord injury (SCI) can cause permanent disabilities that seriously reduce quality of life. We evaluated the effects of chronic hyperglycemia before SCI on inflammatory markers and functional recovery after SCI in human patients and a rat model. In the human study, multivariate logistical regression analysis revealed that hemoglobin A1c (HbA1c) values, reflecting average plasma glucose concentration over a 3 month period, at admission were a significant risk factor for poor functional recovery. Moreover, patients with chronic hyperglycemia (HbA1c ≥ 6.5%) had high concentrations of inflammatory biomarkers (interleukin [IL]-6 and IL-8) of cerebrospinal fluid after SCI. Consistent with patient findings, chronic hyperglycemia before SCI in rats was associated with increased inflammatory responses and oxygen-free radicals in the spinal cord and blood, thus resulting in poor functional recovery and histological outcomes. Tight glucose control before SCI decreased the harmful effects of hyperglycemia after SCI in both human and rat studies. Our findings suggest that chronic hyperglycemia before SCI may be a significant prognostic factor with a negative impact on functional and histological outcomes, highlighting the importance of tight glucose control before SCI.

Gamma Knife Radiosurgery Using Co-Registration with PET-CT and MRI for Recurrent Nasopharyngeal Carcinoma with Previous Radiotherapy : A Single Center 14-Year Experience.

OBJECTIVE: We retrospectively evaluated the efficacy of Gamma Knife radiosurgery (GKS) for recurrent nasopharyngeal carcinoma (NPC) in patients who previously underwent radiotherapy, and analyzed the treatment outcomes over 14 years. METHODS: Ten patients with recurrent NPC who had previously received radiotherapy underwent stereotactic radiosurgery using a Gamma Knife® (Elekta Inc, Atlanta, GA, USA) between 2005 and 2018. The median target volume was 8.2 cm3 (range, 1.7-17.8), and the median radiation dose to the target was 18 Gy (range, 12-30). The median follow-up period was 18 months (range, 6-76 months). Overall and local failure-free survival rates were determined using the Kaplan-Meier method. RESULTS: The NPCs recurred at the primary cancer site in seven patients (70%), as distant brain metastasis in two (20%), and as an extension into brain in one (10%). The recurrent tumors in seven of the 10 patients (70%) were found on the routine follow-up imaging studies. Two patients presented with headache and one with facial pain. Local failure after GKS occurred in five patients (50%) : two of whom died eight and 6 months after GKS, respectively. No adverse radiation effects were noted after GKS. The 1- and 3-year overall survival rates after GKS were 90% and 77%, respectively. The local failure-free survival rates at 6 months, 1 year, and 3 years after GKS were 80%, 48%, and 32%, respectively. The median interval from GKS to local failure was 8 months (range, 6-12). Univariate analysis revealed that using co-registration with positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) was associated with a lower local failure rate of recurrent NPC (p=0.027). CONCLUSION: GKS is an acceptable salvage treatment option for patients with recurrent NPC who previously received radiation therapy. PET-CT and MRI co-registration for dose planning can help achieve local control of recurrent NPC.

Stereotactic Radiosurgery for Dural Arteriovenous Fistulas Involving the Transverse-Sigmoid Sinus : A Single Center Experience and Review of the Literatures.

OBJECTIVE: We retrospectively assessed the efficacy of stereotactic radiosurgery (SRS) for dural arteriovenous fistulas (DAVFs) involving the transverse-sigmoid sinus and analyzed the angiographic and clinical results with our 8-year experience. METHODS: Nine patients with intracranial DAVFs involving the transverse-sigmoid sinus underwent SRS using a Gamma Knife® (Elekta Inc., Atlanta, GA, USA) between 2009 and 2016. Five patients underwent SRS for residual DAVFs after embolization and four patients were treated with SRS alone. The median target volume was 1.9 cm3 (range, 0.8-14.2) and the median radiation dose of the target was 17 Gy (range, 16-20). The median follow-up period was 37 months (range, 7-81). RESULTS: Pulsating tinnitus (33%) was the most common symptom. DAVFs were completely obliterated in four patients (44%) and subtotally obliterated in five (56%). Six patients (67%) showed complete recovery of symptoms or signs, and three (33%) showed incomplete recovery. One patient experienced a recurrent seizure. Adverse radiation effects after SRS occurred in one patient (11%). The total obliteration rates after SRS were 16.7%, 37.5%, and 68.7% at 1, 2, and 3 years, respectively. The median interval from SRS to total obliteration of the fistula was 31 months (range, 12-38). The rates at which the symptoms started to improve were 40% at 1 month and 80% at 2 months after SRS. Symptoms started to improve at a median of 5 weeks after SRS (range, 3-21). CONCLUSION: SRS with or without embolization is a safe and effective treatment to relieve symptoms and obliterate DAVFs on the transverse-sigmoid sinus.

Anti-Migration and Anti-Invasion Effects of Curcumin via Suppression of Fascin Expression in Glioblastoma Cells.

BACKGROUND: The natural compound curcumin was known to inhibit migration and invasion of glioblastoma (GBM) cells. Fascin, a kind of actin-binding proteins, is correlated with migration and invasion of GBM cells. The purpose of this study was to investigate anti-migration and anti-invasion effects of curcumin via suppression of fascin expression in GBM cells. METHODS: U87 cell line was used as an experimental model of GBM. Fascin was quantified by Western blot analysis. And, the signal transducer and activator of transcription 3 (STAT3), known to play an important role in migration and invasion of tumor cells, were analyzed by sandwich-ELISA. Migration and invasion capacities were assessed by attachment, migration and invasion assays. Cellular morphology was demonstrated by immunofluorescence. RESULTS: At various concentrations of curcumin and exposure times, fascin expression decreased. After temporarily exposure to 10 µM/L curcumin during 6 hours as less invasive concentration and time, fascin expression temporarily decreased at 12 hours (18.4%, p=0.024), and since then recovered. And, the change of phosphrylated STAT3 level also reflected the temporarily decreased pattern of fascin expression at 12 hours (19.7%, p=0.010). Attachment, migration, and invasion capacities consistently decreased at 6, 12, and 24 hours. And, immunofluorescence showed the change of shape and the reduction of filopodia formation in cells. CONCLUSION: Curcumin is likely to suppress the fascin expression in GBM cells, and this might be a possible mechanism for anti-migration and anti-invasion effects of Curcumin via inhibition of STAT3 phosphorylation.

Brain Metastasis from Nasopharyngeal Carcinoma Treated with Stereotactic Radiosurgery.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck, and is associated with high recurrence and low survival rates; however, distant brain metastasis from NPC is rare. CASE DESCRIPTION: The authors report 3 cases of brain metastasis from NPC treated with stereotactic radiosurgery (SRS). A 49-year-old woman presented was diagnosed with brain metastasis from NPC, which occurred 53 months after the initial diagnosis of NPC. Brain magnetic resonance imaging (MRI) revealed a well-enhanced large tumor on the frontal lobe, which was treated with SRS. Six months later, brain MRI revealed progression of the tumor. A 44-year-old man had undergone craniotomy and removal of a cerebellar tumor pathologically confirmed as metastasis from NPC. The recurrent brain metastasis was diagnosed via routine MRI follow-up examination 23 months after surgery. Brain MRI revealed a heterogeneously enhanced cerebellar large tumor, which was treated using hypofractionated SRS. Three months later, brain MRI revealed a significant decrease in the tumor size. A 60-year-old man was diagnosed with distant brain metastasis from NPC via routine positron emission tomography follow-up examination 14 months after the initial diagnosis of NPC. Brain MRI confirmed a homogeneously enhanced tumor on the cavernous sinus, which was treated with SRS. Three months later, brain MRI revealed virtual disappearance of the tumor. All 3 patients had undergone concurrent chemoradiotherapy after the initial diagnosis of NPC and underwent salvage SRS for brain metastasis from NPC. CONCLUSIONS: Despite the poor prognosis, salvage SRS was performed for these rare brain metastases from NPC.

Do Serum Vascular Endothelial Growth Factor and Endostatin Reflect Radiological Radiation-Induced Changes After Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations?

OBJECTIVE: The aim of this study was to analyze serum levels of vascular endothelial growth factor (VEGF) and endostatin in patients with cerebral treated by stereotactic radiosurgery (SRS), and to assess their association with radiological radiation-induced changes (RICs). METHODS: To measure serum biomarkers, peripheral venous blood was collected before SRS and 1 week, 1 month, 3 months, and 6 months after SRS. To evaluate RICs, clinical and neuroimaging follow-up were performed concurrently every 6 months after SRS. RESULTS: Twenty-seven patients were enrolled (11 in the group with RIC, 16 in the group without RIC). Serum VEGF and endostatin levels were positively correlated (P = 0.036, r = 0.405). In the group with RIC, the median serum VEGF 6 months after SRS (58.98 pg/mL) was significantly higher than that of the group without RIC (15.17 pg/mL) (P = 0.001). Multivariate analysis revealed that higher VEGF 6 months after SRS (P = 0.001, hazard ratio, 1.032; 95% confidence interval, 1.012-1.052) and lower endostatin 1 month after SRS (P = 0.007, hazard ratio, 0.964; 95% confidence interval, 0.935-0.993) were significantly associated with RICs. CONCLUSIONS: Our results show that serum levels of VEGF 6 months after SRS were higher in the group with RIC. Serum levels of VEGF 6 months and endostatin 1 month after SRS were associated with the radiological RICs. Thus, serial measurements of serum VEGF and endostatin after SRS might help predict RICs in patients with arteriovenous malformation treated by SRS.

Arachnoid Granulations Mimicking Multiple Osteolytic Bone Lesions in the Occipital Bone.

We report a rare case of arachnoid granulations mimicking multiple osteolytic bone lesions. A 66-year-old woman was admitted to a local clinic for a regular checkup. Upon admission, brain CT showed multiple osteolytic lesions in the occipital bone. These needed to be differentiated from multiple osteolytic bone tumor. Subsequent brain MRI revealed that the osteolytic lesions were isointense to cerebrospinal fluid, hyperintense on T2-weighted image, hypointense on T1-weighted image, and with subtle capsules around the osteolytic lesions that were visible after gadolinium injection. A bone scan revealed no radiotracer uptake. The lesions were in both the transverse sinuses and the torcular herophili. With typical radiological appearances of the lesions, the osteolytic lesions were diagnosed as multiple arachnoid granulations. No further treatment was planned. A 1-year follow-up brain CT scan revealed no change. We should consider the possibility of arachnoid granulations when multiple osteolytic lesions are observed in the occipital bone.