[Consciousness Impairment and Left Hemiparesis due to Contrast Medium in the Coil Embolization of Unruptured Large Right Middle Cerebral Artery Aneurysm: A Case Report].

Neurological deficits following coil embolization of anterior circulation aneurysms due to the toxicity of contrast medium are rare. Here, we describe a patient with mild consciousness impairment and left hemiparesis following coil embolization of a large right middle cerebral artery aneurysm without evidence of ischemia or hemorrhage, who recovered completely with conservative treatment. The patient's clinical course and radiological findings led us to conclude that the neurological deficits were due to the toxic effect of contrast medium used during the coil embolization.

Primary extranodal marginal zone mucosa-associated lymphoid tissue-type B-cell lymphoma involving the dura: A case report.

Background: Primary extranodal marginal zone mucosa-associated lymphoid tissue-type B-cell lymphoma (EMZMBCL), which presents as a dural mass, is a rare intracranial tumor that mimics a subdural hematoma or meningioma. Case Description: A 49-year-old woman presented to our hospital with transient right upper limb paresis, dysarthria for 10 min, and ongoing right upper-limb numbness. Computed tomography (CT) of the head revealed extra-axial lesions in the left frontal and parietal lobes. Based on the initial CT findings in the emergency room, an acute subdural hematoma was suspected. However, meningiomas and other intracranial tumors were also listed as differential diagnoses because there was no history of head trauma or coagulation abnormalities on blood examination, and further imaging studies were performed. Imaging findings suggested a subdural neoplastic lesion. A partial resection was performed for the lesion. Based on histopathological and immunohistochemical examinations, the patient was diagnosed with EMZMBCL. Whole-brain and intensity-modulated radiation therapies were administered as adjuvant therapies. The patient was discharged without neurological deficits. Conclusion: EMZMBCL is a rare disease that should be considered in the differential diagnosis of subdural lesions, especially when there is no history of trauma or abnormalities in the coagulation system. The patient had a favorable outcome after selecting radiotherapy as the adjuvant therapy.

Pituitary metastasis of salivary gland carcinoma mimicking hypophysitis: A case report and literature review.

INTRODUCTION: Pituitary metastases from salivary gland carcinomas are rare. Moreover, pituitary metastasis and hypophysitis exhibit neuroimaging similarities that complicate the diagnosis in patients receiving immune checkpoint drugs. PRESENTATION OF CASE: We present a case of pituitary metastasis derived from a sublingual gland carcinoma; this case posed a challenge in the differential diagnosis of hypophysitis. A 52-year-old male patient presented with anorexia and visual disturbances. The patient was previously diagnosed with sublingual gland carcinoma that necessitated surgical intervention consisting of tumor resection and residual lymph node dissection. Subsequently, the patient underwent immune checkpoint blockade therapy following platinum-based chemotherapy. Magnetic resonance imaging revealed the presence of an intrasellar tumor infiltrating the dura mater, cavernous sinus, and pituitary stalk with isointensity on T1 and T2 weighted images and homogeneous gadolinium enhancement. Despite the initial suspicion of hypophysitis, diagnostic treatment with systemic corticosteroids failed to induce significant tumor reduction. Diagnostic clarification was achieved via an endoscopic transsphenoidal biopsy, which confirmed the histological diagnosis of pituitary metastasis from the prior sublingual gland adenocarcinoma. Radiotherapy was administered as a therapeutic intervention. DISCUSSION: The case report highlighted the rarity of metastases from salivary gland carcinoma to the pituitary gland and emphasized the challenges in distinguishing between pituitary metastasis and hypophysitis based on imaging studies alone, particularly in patients receiving immune checkpoint inhibitors. CONCLUSION: Given the rarity of this condition and its neuroimaging similarities with hypophysitis, pathological confirmation is imperative for a definitive diagnosis.

Discovery of a small peptide from combinatorial libraries that can activate the plant immune system by a jasmonic acid signaling pathway.

Plants defend themselves by using an innate immune system that is activated in response to a variety of molecules derived from pathogens. These molecules have provided profound insights into the mechanisms of pathogen recognition and subsequent signaling pathways in plants. In the present study, we screened a combinatorial random hexapeptide library for peptides that activate the plant immune system, by using a cell-based high-throughput screening system in which H(2)O(2) generation was monitored. We discovered a novel small peptide (YGIHTH-amide, PIP-1) that triggered H(2)O(2) production in tobacco and tomato cells, but not in Arabidopsis cells. PIP-1 induced significant levels of phytoalexin biosynthesis and defense-related gene expression in tobacco cells; this is likely to be activated by a jasmonic acid pathway.

Using gene expression profiling to identify a prognostic molecular spectrum in gliomas.

Histopathological classification of gliomas is often clinically inadequate due to the diversity of tumors that fall within the same class. The goal of the present study was to identify prognostic molecular features in diffusely infiltrating gliomas using gene expression profiling. We selected 3456 genes expressed in gliomas, including 3012 genes found in a gliomal expressed sequence tag collection. The expression levels of these genes in 152 gliomas (100 glioblastomas, 21 anaplastic astrocytomas, 19 diffuse astrocytomas, and 12 anaplastic oligodendrogliomas) were measured using adapter-tagged competitive polymerase chain reaction, a high-throughput reverse transcription-polymerase chain reaction technique. We applied unsupervised and supervised principal component analyses to elucidate the prognostic molecular features of the gliomas. The gene expression data matrix was significantly correlated with the histological grades, oligo-astro histology, and prognosis. Using 110 gliomas, we constructed a prediction model based on the expression profile of 58 genes, resulting in a scheme that reliably classified the glioblastomas into two distinct prognostic subgroups. The model was then tested with another 42 tissues. Multivariate Cox analysis of the glioblastoma patients using other clinical prognostic factors, including age and the extent of surgical resection, indicated that the gene expression profile was a strong and independent prognostic parameter. The gene expression profiling identified clinically informative prognostic molecular features in astrocytic and oligodendroglial tumors that were more reliable than the traditional histological classification scheme.

Cyclic dipeptide of D-ornithine obtained from the dobsonfly, Protohermes grandis Thunberg.

A new compound was isolated from the water-soluble fraction of a methyl alcohol extract obtained from the larva of the dobsonfly (Protohermes grandis Thunberg). The novel compound had a 12-membered ring and was confirmed to be a cyclic dipeptide of D-ornithine by a chiral analysis, using high-performance liquid chromatography, 2D-nuclear magnetic resonance, and field desorption mass spectrometry.

Gene expression-based molecular diagnostic system for malignant gliomas is superior to histological diagnosis.

PURPOSE: Current morphology-based glioma classification methods do not adequately reflect the complex biology of gliomas, thus limiting their prognostic ability. In this study, we focused on anaplastic oligodendroglioma and glioblastoma, which typically follow distinct clinical courses. Our goal was to construct a clinically useful molecular diagnostic system based on gene expression profiling. EXPERIMENTAL DESIGN: The expression of 3,456 genes in 32 patients, 12 and 20 of whom had prognostically distinct anaplastic oligodendroglioma and glioblastoma, respectively, was measured by PCR array. Next to unsupervised methods, we did supervised analysis using a weighted voting algorithm to construct a diagnostic system discriminating anaplastic oligodendroglioma from glioblastoma. The diagnostic accuracy of this system was evaluated by leave-one-out cross-validation. The clinical utility was tested on a microarray-based data set of 50 malignant gliomas from a previous study. RESULTS: Unsupervised analysis showed divergent global gene expression patterns between the two tumor classes. A supervised binary classification model showed 100% (95% confidence interval, 89.4-100%) diagnostic accuracy by leave-one-out cross-validation using 168 diagnostic genes. Applied to a gene expression data set from a previous study, our model correlated better with outcome than histologic diagnosis, and also displayed 96.6% (28 of 29) consistency with the molecular classification scheme used for these histologically controversial gliomas in the original article. Furthermore, we observed that histologically diagnosed glioblastoma samples that shared anaplastic oligodendroglioma molecular characteristics tended to be associated with longer survival. CONCLUSIONS: Our molecular diagnostic system showed reproducible clinical utility and prognostic ability superior to traditional histopathologic diagnosis for malignant glioma.

Severe Hypoglycemia-induced Right Hemiparesis with Reversible Diffusion Restriction in the Left Internal Capsule Due to Combination Therapy Using Disopyramide and Clarithromycin.

Severe hypoglycemia is known to cause acute focal neurological symptoms. In cases with a medical history of diabetes mellitus (DM), the diagnosis and treatment of hypoglycemia-induced neurological symptoms are simple. However, severe hypoglycemia can occur in patients who are not taking hypoglycemic agents such as insulin or long-acting sulfonylurea drugs. We describe a 95-year-old man with sudden onset of right hemiparesis who showed high signal intensity on diffusion-weighted imaging involving the left internal capsule with corresponding reduced apparent diffusion coefficient hypointensity. Laboratory findings revealed severe hypoglycemia (27 mg/dl). However, he was not taking insulin or long-acting sulfonylurea drugs but disopyramide and clarithromycin had been administered. In addition, he had kidney dysfunction with an estimated glomerular filtration rate (GFR) of 42.9 ml/min/1.73 m2. After the blood glucose level was normalized, the left hemiparesis completely recovered and abnormal findings of magnetic resonance imaging (MRI) study also became normal. A combination of disopyramide and clarithromycin may cause severe hypoglycemia-induced neurological symptoms particularly in patients with kidney dysfunction. Even in a patient with sudden-onset hemiparesis and no history of DM, the possibility of hypoglycemia-induced neurological deficit should be considered.

Effect of choice of treatment modality on the incidence of shunt-dependent hydrocephalus after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Shunt-dependent hydrocephalus (SDHC) may arise after aneurysmal subarachnoid hemorrhage (aSAH) as CSF resorptive mechanisms are disrupted. Using propensity score analysis, the authors aimed to investigate which treatment modality, surgical clipping or endovascular treatment, is superior in reducing rates of SDHC after aSAH. METHODS: The authors' multicenter SAH database, comprising 3 stroke centers affiliated with Kyoto University, Japan, was used to identify patients treated between January 2009 and July 2016. Univariate and multivariate analyses were performed to characterize risk factors for SDHC after aSAH. A propensity score model was generated for both treatment groups, incorporating relevant patient covariates to detect any superiority for prevention of SDHC after aSAH. RESULTS: A total of 566 patients were enrolled in this study. SDHC developed in 127 patients (22%). On multivariate analysis, age older than 53 years, the presence of intraventricular hematoma, and surgical clipping as opposed to endovascular coiling were independently associated with SDHC after aSAH. After propensity score matching, 136 patients treated with surgical clipping and 136 with endovascular treatment were matched. Propensity score-matched cohorts exhibited a significantly lower incidence of SDHC after endovascular treatment than after surgical clipping (16% vs 30%, p = 0.009; OR 2.2, 95% CI 1.2-4.2). SDHC was independently associated with poor neurological outcomes (modified Rankin Scale score 3-6) at discharge (OR 4.3, 95% CI 2.6-7.3; p < 0.001). CONCLUSIONS: SDHC after aSAH occurred significantly more frequently in patients who underwent surgical clipping. Strategies for treatment of ruptured aneurysms should be used to mitigate SDHC and minimize poor outcomes.

Development of a high-throughput screening method using a cell-based, lawn format assay for the identification of novel plant defense activators from combinatorial peptide libraries.

Plants respond to attack by pathogens through various defense mechanisms. These defense responses are triggered by a variety of molecules derived from pathogenic microorganisms as well as host plants. In this study, we developed a high-throughput screening method using a cell-based lawn format assay for the identification of novel peptides that can induce plant defense responses from combinatorial peptide libraries. Solid-phase peptide libraries were synthesized using a photocleavable linker and immobilized using agarose gel. The peptides were partially cleaved from beads, and the agarose gel was layered on the tobacco cells. The defense response was then observed by detecting the generated H2O2 using a sensitive H2O2 indicator dye, N-(carboxymethylaminocarbonyl)-4,4'-bis(dimethylamino)diphenylamine sodium salt (DA-64). Using this assay format, a 6859-member peptide library based on the sequence of flagellin-derived peptides was screened, and several structural features important for the activity were obtained.

Phase I/II Study of Temozolomide Plus Nimustine Chemotherapy for Recurrent Malignant Gliomas: Kyoto Neuro-oncology Group.

The objective of this phase I/II study was to examine the efficacy and toxicity profile of temozolomide (TMZ) plus nimustine (ACNU). Patients who had received a standard radiotherapy with one or two previous chemo-regimens were enrolled. In phase I, the maximum-tolerated dose (MTD) by TMZ (150 mg/m2/day) (Day 1-5) plus various doses of ACNU (30, 35, 40, 45 mg/m2/day) (Day 15) per 4 weeks was defined on a standard 3 + 3 design. In phase II, these therapeutic activity and safety of this regimen were evaluated. Forty-nine eligible patients were enrolled. The median age was 50 years-old. Eighty percent had a KPS of 70-100. Histologies were glioblastoma (73%), anaplastic astrocytoma (22%), anaplastic oligodendroglioma (4%). In phase I, 15 patients were treated at four cohorts by TMZ plus ACNU. MTD was TMZ (150 mg/m2) plus ACNU (40 mg/m2). In phase II, 40 patients were treated at the dose of cohort 3 (MTD). Thirty-five percent of patients experienced grade 3 or 4 toxicities, mainly hematologic. The overall response rate was 11% (4/37). Sixty-eight percent (25/37) had stable disease. Twenty-two percent (8/37) showed progression. Progression-free survival (PFS) rates at 6 and 12 months were 24% (95% CI, 12-35%) and 8% (95% CI, 4-15%). Median PFS was 13 months (95% CI, 9.2-17.2 months). Overall survival (OS) at 6 and 12 were 78% (95% CI, 67-89%) and 49% (95% CI, 33-57%). Median OS was 11.8 months (95% CI, 8.2-14.5 months). This phase I/II study showed a moderate toxicity in hematology and may has a promising efficacy in OS, without inferiority in PFS.

Dural arteriovenous fistula in the falx cerebri treated with transarterial embolization using n-butyl cyanoacrylate.

BACKGROUND: A dural arteriovenous fistula in the falx cerebri is a relatively rare lesion, with only two cases reported till date. One was treated with direct surgery, and the other was followed-up conservatively. Advances in catheter design and embolic materials have made safe and curative transarterial embolization of dural arteriovenous fistulas possible in the current era. CASE DESCRIPTION: We describe a 67-year-old man with left putaminal hemorrhage who was diagnosed with an arteriovenous fistula in the anterior part of the falx cerebri that was treated with curative transarterial glue embolization through the middle meningeal artery by using n-butyl cyanoacrylate. CONCLUSION: Although the procedure was safely performed, understanding the potential risks of the migration of embolic materials into the ophthalmic and anterior cerebral artery system is mandatory.

Metastatic brain tumor from urothelial carcinoma of the prostatic urethra.

BACKGROUND: Urothelial carcinoma occurs in the bladder, upper urinary tract, and lower urinary tract, including prostatic urethra. A majority of the reported cases of intracranial metastasis from urothelial carcinoma originates from the bladder and upper urinary tract. Brain metastasis from urothelial carcinoma of the prostatic urethra has not yet been reported in the literature. CASE DESCRIPTION: A 72-year-old male presented with a metastatic brain tumor and a 3-year history of urothelial carcinoma of the prostatic urethra treated with cystourethrectomy and chemotherapy with gemcitabine-cisplatin. Pathological diagnosis for tumor removal was compatible with metastatic brain tumor from urothelial carcinoma. CONCLUSION: Brain metastasis from urothelial carcinoma of the prostatic urethra has not yet been reported in the literature. It is an extremely rare case, however, we should be careful of brain metastasis during follow-up for urothelial carcinoma in the lower urinary tract.

Rendu-Osler-Weber disease with a giant intracerebral varix secondary to a high-flow pial AVF: case report.

BACKGROUND: Intracranial varices are rare and most are associated with vein of Galen arteriovenous malformations (AVM) or fistulas (AVF). DESCRIPTION: A 43-year-old left-handed man presented with right hemihypesthesia and spastic gait. Neuroradiological examination revealed a spinal AVF and a giant intracerebral varix associated with a high-flow pial AVF. He had recurrent episodes of nasal bleeding, which were also confirmed in his mother's medical history, and telangiectases in the tip of his tongue and fingers. He was diagnosed with Rendu-Osler-Weber disease. After resection of the spinal AVF that produced his symptoms, we surgically exposed and obliterated the giant varix and AVF under intra- and postoperative hypotension and mild barbiturate therapy. The arteriovenous shunt was completely obliterated without hyperperfusion of the surrounding brain. CONCLUSION: This is an extremely rare case of Rendu-Osler-Weber disease with a giant intracerebral varix secondary to a high-flow pial AVF that did not involve the vein of Galen.

Intraprocedural detection of cerebral hyperperfusion by flat detector computed tomography in the evaluation of cerebral blood volume during carotid artery stenting. A case report.

Cerebral blood volume (CBV) can be measured using a C-arm flat detector angiographic system. The present report describes a case in which cerebral hyperperfusion was detected with the Neuro parenchymal blood volume (PBV) system (syngo Neuro PBV IR, Siemens Medical Solutions, Erlangen, Germany) during carotid artery stenting (CAS). An 89-year-old man was referred to our hospital for cerebral brain infarction and severe stenosis of the left carotid artery. CAS was performed, and Neuro PBV was used to measure CBV both during and after the procedure. Postoperative Neuro PBV revealed dramatically increased CBV, and a hyperperfusion state was suspected. The next day, subarachnoid hemorrhage along the sulcus of the left hemisphere was revealed on computed tomography. Strict management of blood pressure was instituted just after the detection of hyperperfusion, and the patient was ultimately discharged from the hospital without any new neurological deficits. Neuro PBV has the advantage that it can be performed in the angiography suite and does not require patient transfer to an alternate setting. Therefore, intracranial hemodynamic changes can be detected during the procedure. We conclude that the Neuro PBV system is useful for monitoring intracranial hemodynamics during endovascular procedures.

Increased expression of aquaporin 1 in human hemangioblastomas and its correlation with cyst formation.

Aquaporins (AQPs) is a water channel family which facilitates the passage of water across cell membranes. Recently, expression of aquapporin 1 (AQP1) was found to be involved in not only water transport but also tumorigenesis. In present study, we analyzed the expression of AQP1 in 26 consecutive cases of human hemangioblastomas. Significant upregulation of AQP1 expression was found in hemangioblastomas compared with control brain (P=0.002). In hemangioblastomas, expression of AQP1 was predominantly localized on membranes of stromal cells. The expression level of AQP1 in cystic group of hemangioblastomas is much higher than that of solid group (P=0.021). Most hemangioblastomas showed a negative expression of AQP1 on endothelial cells. These results imply that increased expression of AQP1 in stromal cells may play a role in cyst formation and tumorigenesis of heman-gioblastomas.

Quantitative analysis of topoisomerase IIalpha to rapidly evaluate cell proliferation in brain tumors.

Immunohistochemical cell proliferation analyses have come into wide use for evaluation of tumor malignancy. Topoisomerase IIalpha (topo IIalpha), an essential nuclear enzyme, has been known to have cell cycle coupled expression. We here show the usefulness of quantitative analysis of topo IIalpha mRNA to rapidly evaluate cell proliferation in brain tumors. A protocol to quantify topo IIalpha mRNA was developed with a real-time RT-PCR. It took only 3 h to quantify from a specimen. A total of 28 brain tumors were analyzed, and the level of topo IIalpha mRNA was significantly correlated with its immuno-staining index (p<0.0001, r=0.9077). Furthermore, it sharply detected that topo IIalpha mRNA decreased in growth-inhibited glioma cell. These results support that topo IIalpha mRNA may be a good and rapid indicator to evaluate cell proliferate potential in brain tumors.