The effect of 24-week continuous intake of quercetin-rich onion on age-related cognitive decline in healthy elderly people: a randomized, double-blind, placebo-controlled, parallel-group comparative clinical trial.

Quercetin, a type of flavonoid, is believed to reduce age-related cognitive decline. To elucidate its potential function, we carried out a randomized, double-blind, placebo-controlled, parallel-group comparative clinical trial involving 24-week continuous intake of quercetin-rich onion compared to quercetin-free onion as a placebo. Seventy healthy Japanese individuals (aged 60 to 79 years old) were enrolled in this study. We examined the effect of quercetin-rich onion (the active test food) on cognitive function using the Mini-Mental State Examination, Cognitive Assessment for Dementia iPad version, and Neuropsychiatric Inventory Nursing Home version. The Mini-Mental State Examination scores were significantly improved in the active test food group (daily quercetin intake, 50 mg as aglycone equivalent) compared to the placebo food group after 24 weeks. On the Cognitive Assessment for Dementia iPad version for emotional function evaluation, we found that the scores of the active test food group were significantly improved, suggesting that quercetin prevents cognitive decline by improving depressive symptoms and elevating motivation. On the Neuropsychiatric Inventory Nursing Home version, we found significant effects on reducing the burden on study partners. Taking all the data together, we concluded that 24-week continuous intake of quercetin-rich onion reduces age-related cognitive decline, possibly by improving emotional conditions. Clinical trial register and their clinical registration number: This study was registered with UMIN (approval number UMIN000036276, 5 April 2019).

Discovery of Power-Law Growth in the Self-Renewal of Heterogeneous Glioma Stem Cell Populations.

BACKGROUND: Accumulating evidence indicates that cancer stem cells (CSCs) drive tumorigenesis. This suggests that CSCs should make ideal therapeutic targets. However, because CSC populations in tumors appear heterogeneous, it remains unclear how CSCs might be effectively targeted. To investigate the mechanisms by which CSC populations maintain heterogeneity during self-renewal, we established a glioma sphere (GS) forming model, to generate a population in which glioma stem cells (GSCs) become enriched. We hypothesized, based on the clonal evolution concept, that with each passage in culture, heterogeneous clonal sublines of GSs are generated that progressively show increased proliferative ability. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, we determined whether, with each passage, glioma neurosphere culture generated from four different glioma cell lines become progressively proliferative (i.e., enriched in large spheres). Rather than monitoring self-renewal, we measured heterogeneity based on neurosphere clone sizes (#cells/clone). Log-log plots of distributions of clone sizes yielded a good fit (r>0.90) to a straight line (log(% total clones) = k*log(#cells/clone)) indicating that the system follows a power-law (y = xk) with a specific degree exponent (k = -1.42). Repeated passaging of the total GS population showed that the same power-law was maintained over six passages (CV = -1.01 to -1.17). Surprisingly, passage of either isolated small or large subclones generated fully heterogeneous populations that retained the original power-law-dependent heterogeneity. The anti-GSC agent Temozolomide, which is well known as a standard therapy for glioblastoma multiforme (GBM), suppressed the self-renewal of clones, but it never disrupted the power-law behavior of a GS population. CONCLUSIONS/SIGNIFICANCE: Although the data above did not support the stated hypothesis, they did strongly suggest a novel mechanism that underlies CSC heterogeneity. They indicate that power-law growth governs the self-renewal of heterogeneous glioma stem cell populations. That the data always fit a power-law suggests that: (i) clone sizes follow continuous, non-random, and scale-free hierarchy; (ii) precise biologic rules that reflect self-organizing emergent behaviors govern the generation of neurospheres. That the power-law behavior and the original GS heterogeneity are maintained over multiple passages indicates that these rules are invariant. These self-organizing mechanisms very likely underlie tumor heterogeneity during tumor growth. Discovery of this power-law behavior provides a mechanism that could be targeted in the development of new, more effective, anti-cancer agents.

Syringomyelia associated with Paget disease of the skull.

A 38-year-old man presented with a rare case of syringomyelia associated with Paget disease of the skull. Syringosubarachnoid (SS) shunting was performed. We speculate that deformation of the skull secondary to Paget disease caused narrowing of the foramen magnum with progressive impairment of the cerebrospinal fluid circulation, which led to syringomyelia and neurological symptoms. SS shunting is safe, effective, and technically simple, so may be a useful initial treatment for syringomyelia associated with Paget disease of the skull.

Prognostic significance of sirtuin 2 protein nuclear localization in glioma: an immunohistochemical study.

The sirtuin 2 (SIRT2) protein is a member of the sirtuin family and homologous to Sir2 (silent information regulator 2) of Saccharomyces cerevisiae. To assess the pathobiological significance of SIRT2 protein expression and/or subcellular localization in human glioma, we examined SIRT2 protein expression in human gliomas using a polyclonal anti-SIRT2 antibody and immunohistochemistry. In this study, samples from 23 patients with glioblastoma (GB, grade IV), 8 patients with diffuse astrocytoma (DA, grade II) and 5 healthy individuals were examined. We established a SIRT2 labeling index (SIRT2-LI) that represents the percentage of cells with SIRT2 localized to the nucleus. The mean SIRT2-LI was 65.8±18.6 in GB samples, 41.2±22.8 in DA samples, and 28.6±12.3 in normal control samples. The SIRT2-LI of GB samples was significantly higher than that of normal control samples (P<0.01, Mann-Whitney's U-test) and that of DA samples (P<0.05). Moreover, the SIRT2-LI was positively correlated with malignant progression. Specifically, samples from patients with GB were divided into two groups, low SIRT2-LI (<60%) and high SIRT2-LI (≥60%), and the patients with low SIRT2-LI samples survived significantly longer than patients with high SIRT2-LI samples (P<0.05, Kaplan-Meier method and log-rank test). In conclusion, SIRT2-LI was indicative of glioma malignancy, and it may be predictive of GB patient survival.

Thoracic vertebral cavernous hemangioma in a schizophrenic patient--case report.

A 55-year-old man presented with gait disturbance, incontinence, and back pain. He had a medical history of schizophrenia for the past 35 years. Computed tomography (CT) and magnetic resonance imaging suggested thoracic vertebral hemangioma. Dynamic CT incidentally detected a hepatic hemangioma. Laminectomy of T3 and T4, resection of the epidural hemangioma, and rigid instrumentation between T1 and T6 using rod and hook systems were performed. Postoperatively, his symptoms completely disappeared and the histological diagnosis was capillary hemangioma. Schizophrenic patients have diminished sensitivity to pain or other symptoms, so neurological symptoms may become severe. However, early and appropriate treatment can result in satisfactory neurological outcome. The patient had a rare association of vertebral hemangioma and hepatic hemangioma, which may be a chance occurrence.

Anomia for people's names after left anterior temporal lobe resection--case report.

A 47-year-old man was admitted to our hospital with an intrinsic brain tumor in the left anterior temporal lobe. Preoperative sodium thiopental test demonstrated left hemispheric dominance. Awake craniotomy was performed for dominant-hemispheric tumor resection using language mapping to identify the stimulation-induced positive language area. The tasks of object naming and repetition were used, along with specific tests for famous people's names. The language area was detected on the superior temporal gyrus and preserved. Following surgery, this patient was unable to retrieve the names of famous individuals (i.e. anomia for people's name) despite preservation of semantic knowledge for those individuals. This anomia for people's names showed no improvement at all for a period of 15 months. This case report and other sporadic cases with this type of deficit reveal the left anterior temporal lobe is an important brain area for retrieving people's names.

Neuropsychological changes after endoscopic third ventriculostomy for long-standing overt ventriculomegaly in adults. Case report.

A 39-year-old woman presented with long-standing overt ventriculomegaly in adults (LOVA) manifesting as gradually worsening headache. Past history included treatment for myeloschisis at birth. Intelligence quotient (IQ) was 115 and preoperative psychological assessment using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) showed normal scores in all domains. However, scores for constructional ability were slightly low. Computed tomography revealed severe ventriculomegaly involving the lateral and third ventricles, and magnetic resonance imaging showed aqueductal stenosis. Endoscopic third ventriculostomy was performed under a diagnosis of LOVA. Postoperatively, the headache resolved and the RBANS showed improvements in memory and constructional ability. Detailed evaluation of cognitive function provides a good indicator in the treatment of hydrocephalus with normal IQ.

A rare astrocytic tumor with rhabdoid features.

We report an extremely rare tumor presenting with rhabdoid features in the left temporoparietal lobe near the trigone in an 18-year-old Japanese man. This tumor mainly consisted of medium to large round cells that proliferated diffusely and incoherently with a scant extracellular matrix. These tumor cells had an eccentric nucleus and an eosinophilic cytoplasm containing inclusion bodies and bundles of intermediate filaments. The nuclei of these cells were vesicular with prominent nucleoli. This tumor had an area appearing to be diffuse astrocytoma peripherally and lacked a primitive neuroectodermal tumor component, a mesenchymal component, and epithelial differentiation. INI expression, which is not observed in atypical teratoid/ rhabdoid tumor (AT/RT), was found in this tumor. From these findings, we concluded that this tumor was not AT/RT but an astrocytic tumor with rhabdoid features. We also concluded that the tumor cells exhibiting rhabdoid features had secondarily arisen from the peripheral area presenting an appearance of diffuse astrocytoma.

Folliculostellate cell tumor in pituitary gland.

A 33-year-old woman presented with visual field defects. Magnetic resonance imaging demonstrated a pituitary tumor with suprasellar extension. The tumor was partially removed by trans-sphenoidal surgery. Histologically, the tumor was composed of fascicles of spindle cells which were immunohistochemically positive for S-100 protein, Galectin-3, vimentin and EMA. Based on the morphology and immunostaining pattern, diagnosis of folliculostellate cell tumor in the pituitary gland was given.

Malignant transformation of supratentorial clear cell ependymoma.

Recurrence of clear cell ependymoma is not a rare condition, but malignant transformation of clear cell ependymoma has not yet been well presented. The authors report a 44-year-old man who presented with progressive right hemiparesis. A brain tumor in the left frontal premotor area was removed and an initial pathological diagnosis of oligodendroglioma was made. The tumor recurred 4 months later, and reoperation of the tumor and adjuvant local radiotherapy were performed. The patient subsequently underwent surgical removal of recurrent tumors on another four occasions (6 times in total) during a period of 11 years and finally died of the original disease. Histopathological studies of all surgical and autopsy specimens were carried out. The first and second surgical specimens did not contain any ependymal rosettes or pseudorosettes, and thus a diagnosis of oligodendroglioma was made. However, the third surgical specimen showed pseudorosettes. At this time, the tumor had an ultrastructural appearance compatible with ependymoma. Thereafter, the recurrent tumors showed anaplastic features such as nuclear pleomorphisms and necrosis with pseudopallisading. The autopsy specimens resembled a feature of glioblastoma but the tumor was sharply demarcated from the surrounding parenchyma.

Induction of autophagic cell death and radiosensitization by the pharmacological inhibition of nuclear factor-kappa B activation in human glioma cell lines.

OBJECT: The intrinsic radioresistance of certain cancer cells may be closely associated with the constitutive activation of nuclear factor-kappa B (NF-kappaB) activity, which may lead to protection from apoptosis. Recently, nonapoptotic cell death, or autophagy, has been revealed as a novel response of cancer cells to ionizing radiation. In the present study, the authors analyzed the effect of pitavastatin as a potential inhibitor of NF-kappaB activation on the radiosensitivity of A172, U87, and U251 human glioma cell lines. METHODS: The pharmacological inhibition of NF-kappaB activation was achieved using pitavastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Growth and radiosensitivity assays were performed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Hoechst 33258 staining, supravital acridine orange staining, and electron microscopy were performed utilizing 3 glioma cell lines with or without pitavastatin pretreatment to identify apoptosis or autophagy after irradiation. RESULTS: The growth of these 3 glioma cell lines was not significantly inhibited by pitavastatin at a concentration of up to 1 microM. Treatment with 0.1 microM of pitavastatin enhanced radiation-induced cell death in all glioma cell lines, with different sensitivity. Apoptosis did not occur in any pretreated or untreated (no pitavastatin) cell line following irradiation. Instead, autophagic cell changes were observed regardless of the radiosensitivity of the cell line. An inhibitor of autophagy, 3-methyladenine suppressed the cytotoxic effect of irradiation with pitavastatin, indicating that autophagy is a result of an antitumor mechanism. Using the most radiosensitive A172 cell line, the intracellular localization of p50, a representative subunit of NF-kappaB, was evaluated through immunoblotting and immunofluorescence studies. The NF-kappaB of A172 cells was immediately activated and translocated from the cytosol to the nucleus in response to irradiation. Pitavastatin inhibited this activation and translocation of NF-kappaB. CONCLUSIONS: Autophagic cell death rather than apoptosis is a possible mechanism of radiation-induced and pitavastatin-enhanced cell damage, and radiosensitization by the pharmacological inhibition of NF-kappaB activation may be a novel therapeutic strategy for malignant gliomas.

Giant plexiform neurofibroma and suboccipital meningocele manifesting as segmental neurofibromatosis.

A 34-year-old woman presented with segmental neurofibromatosis manifesting as a soft lump with a large café-au-lait macule on her occipital region and neck. Magnetic resonance imaging showed a thick skin tumor in the occipital region and posterior neck, and a suboccipital meningocele which seemed to have no association with her symptoms. Biopsy lead to a histological diagnosis of giant plexiform neurofibroma. During biopsy, massive local bleeding occurred and hemostasis was achieved by electrocautery and meticulous suture ligation. The postoperative course was uneventful and observation was continued for both the giant plexiform neurofibroma and the meningocele.

Pilomyxoid astrocytoma in a patient presenting with fatal hemorrhage. Case report.

The authors report on a rare case of pilomyxoid astrocytoma in a patient presenting with fatal hemorrhage. This 5-year-old boy presented to the outpatient clinic with headache and vomiting. Computed tomography and magnetic resonance imaging studies revealed a mass lesion with partial hemorrhage in the suprasellar region extending into the third ventricle. Partial resection via a transcallosal approach was performed. Because the pathological diagnosis was pilomyxoid astrocytoma, chemotherapy was administered. However, 4 months after the first operation, during chemotherapy, the boy presented with massive intratumoral and intraventricular hemorrhage with hydrocephalus. Although emergent external ventricular drainage was performed, the patient died. In this report, the authors review the literature and discuss the clinical features and treatment of pilomyxoid astrocytoma.

Involvement of meteorological factors and sex in the occurrence of subarachnoid hemorrhage in Japan.

The sex difference in the seasonal occurrence of subarachnoid hemorrhage (SAH) and the association of meteorological factors in Japan were analyzed in 1006 consecutive patients with SAH in Toyama, Japan from 1996 to 2000. The study investigated whether these meteorological factors could explain the seasonality of the incidence of SAH in each sex. Seasonal variation of SAH occurrence peaked in spring in men, but peaked in spring and winter in women. The difference between maximum temperature and minimum temperature was the greatest on the day previous to SAH occurrence in multiple individuals in men, whereas mean humidity was the greatest on that day in women. Interestingly, the difference between maximum temperature and minimum temperature peaked in spring and mean humidity in winter from the meteorological data over the 5 years. The relationship between humidity and occurrence of SAH may explain the sex difference of the incidence of aneurysmal SAH. The humidity change may be a specific and additional meteorological factor for the incidence of SAH in women.

Preparation of a simple and efficient laboratory model for training in neuroendoscopic procedures.

OBJECTS: Because the lateral ventricles of cadaver heads are often collapsed, they can be difficult to cannulate endoscopically. We present a novel method for preparing a cadaveric model for endoscopic intraventricular procedures. MATERIALS AND METHODS: A burr hole was placed in the midpupillary line anterior to the coronal suture. A triangular wedge of frontal scalp, skull, and dura with its base 6 cm superior to the orbitomeatal line and 6 cm posterior to the forehead was cut and removed. A wedge of the underlying brain was similarly cut along the edge of the bone window. After removal of the brain block, the anterior horn of the lateral ventricle was exposed. The endoscope sheath was inserted through the burr hole into the anterior horn in the brain block, following its return to its original location with the skull and scalp. CONCLUSION: This model is easily prepared and optimizes training in endoscopic ventricular surgery.

Malignant transformation of oligoastrocytoma: a case report.

We report a case of oligoastrocytoma resembling dysembryoplastic neuroepithelial tumor (DNT) with malignant transformation. A 35-year-old woman presented with headache and generalized convulsion in May 2003. Magnetic resonance imaging (MRI) revealed an extensive left temporal lobe tumor. She underwent partial resection of the tumor under awake surgery, while preserving her language function. The surgical specimen showed that the majority of the tumor was composed of a glioneuronal element. However, there was also an abundant oligoastrocytoma component. Therefore, our first pathological diagnosis was oligoastrocytoma and DNT. She then underwent radiation therapy. The tumor recurred at the left temporal lobe in June 2005. She then underwent open biopsy. The pathological diagnosis was anaplastic oligoastrocytoma with a MIB-1 staining index of 79%. She received PAV (procarvazine, ACNU, and vincristine) chemotherapy, and the tumor subsided transiently. However, she died 3 years after the first operation. Although the histological findings of the first surgical specimen closely resembled those of DNT, radiologic findings and clinical course were different from those of DNT. The authors concluded that this tumor could be a malignant transformation of oligoastrocytoma mimicking DNT, and we wish to give warning that the presence of a glioneuronal component is not an absolute benign hallmark.

Recurrent intracranial solitary fibrous tumor initially diagnosed as hemangiopericytoma.

We describe a case of an intracranial solitary fibrous tumor that recurred three times consecutively in an 11-year period. A 72-year-old man presented with a headache and gait disturbance. Magnetic resonance imaging (MRI) revealed a dumbbell tumor at the left tentorium. The tumor was removed but recurred. The first diagnosis was hemangiopericytoma, but all specimens showed a "patternless pattern" and few reticulin fibers, which features were not compatible with hemangiopericytoma. All tumors showed immunoreactivity for CD34 and bcl-2. These results point to a solitary fibrous tumor (SFT) and not to hemangiopericytoma. We present here a hypercellular spindle-cell tumor that was very similar to hemangiopericytoma but is better diagnosed as SFT.

Prognostic factors in elderly patients with supratentorial malignant gliomas.

The prognostic factors were retrospectively analyzed in 30 patients aged 70 years or over with supratentorial malignant gliomas treated by surgery in our hospital. The histological diagnosis was confirmed as grade 3 in 13 patients and grade 4 in 17. Seventeen patients received adjuvant radiation therapy. Only 10 patients underwent chemotherapy. Survival time was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from the Cox proportional hazards model. Univariate analysis showed preoperative Karnofsky performance status (KPS) score of 70 or greater and radiation therapy were significantly associated with longer survival. However, multivariate analysis revealed that preoperative KPS score of 70 or greater was the only independent prognostic factor and radiation therapy lost its significance due to selection bias. Neurological deterioration and medical complications occurred in six and seven patients, respectively. Performance status rather than histological grade is the key prognostic factor in elderly patients with supratentorial malignant gliomas. Patients with good preoperative KPS score should be aggressively treated with extensive resection and radiotherapy.

Intraosseous cavernous hemangioma of the frontal bone.

A 32-year-old man presented with a primary intraosseous cavernous hemangioma manifesting as a small painless swelling of the right forehead. Radiography revealed a radiolucent osteolytic lesion in the right frontal region. Bone window computed tomography demonstrated a 1.5 cm mass between the outer and inner tables just lateral to the right frontal sinus. The outer and inner tables were thin and partially defective, but without bone fracture. Magnetic resonance imaging revealed a small mass lesion with bone erosion of the posterior table of the frontal bone. Preoperative examination yielded no final diagnosis. En bloc resection was performed. The histological diagnosis was primary intraosseous cavernous hemangioma. Total resection is recommended for definitive diagnosis of intraosseous tumor.