Combined endoscopic endonasal and transcranial approach for internal carotid artery aneurysms: usefulness and safety of endonasal proximal control.

It is necessary to secure both the proximal and distal sides of the parent artery to prevent premature rupture when clipping cerebral aneurysms. Herein, we describe four cases in which the proximal internal carotid artery (ICA), affected by a paraclinoid aneurysm, was secured using an endoscopic endonasal approach. We used various tools, including a surgical video, cadaver dissection picture, artist's illustration, and intraoperative photographs, to elucidate the process. No patient experienced postoperative complications at our institution. Compared to the cervical or cavernous ICA, the ICA adjacent to the clivus (paraclival ICA) can be anatomically safely and easily exposed using an endoscopic endonasal approach because there is no need to consider cerebrospinal fluid leakage or hemorrhage from the cavernous sinus. Securing the proximal side of the parent artery using an endoscopic endonasal approach may be a viable method for clipping selected ICA aneurysms, such as paraclinoid aneurysms especially for upward or outward aneurysms of the C2 portion.

Aberrant expression of claudin-6 contributes to malignant potentials and drug resistance of cervical adenocarcinoma.

Recent studies have revealed that aberrant expression of tight junction (TJ) proteins is a hallmark of various solid tumors and it is recognized as a useful therapeutic target. Claudin-6 (CLDN6), a member of the family of TJ transmembrane proteins, is an ideal therapeutic target because it is not expressed in human adult normal tissues. In this study, we found that CLDN6 is highly expressed in uterine cervical adenocarcinoma (ADC) and that high CLDN6 expression was correlated with lymph node metastasis and lymphovascular infiltration and was an independent prognostic factor. Shotgun proteome analysis revealed that cell-cell adhesion-related proteins and drug metabolism-associated proteins (aldo-keto reductase [AKR] family proteins) were significantly increased in CLDN6-overexpressing cells. Furthermore, overexpression of CLDN6 enhanced cell-cell adhesion properties and attenuated sensitivity to anticancer drugs including doxorubicin, daunorubicin, and cisplatin. Taken together, the results indicate that aberrant expression of CLDN6 enhances malignant potentials and drug resistance of cervical ADC, possibly due to increased cell-cell adhesion properties and drug metabolism. Our findings provide an insight into a new therapeutic strategy, a CLDN6-targeting therapy, against cervical ADC.

Accumulation of Macromolecules in Idiopathic Normal Pressure Hydrocephalus.

The clearance system in the brain is not completely understood. The aim of this study was to prove the presence of the "glymphatic system" in the human brain using magnetic resonance spectroscopy (MRS).Spectral data of the brain white matter were obtained from healthy volunteers and patients with hydrocephalic dementia and used to measure intracerebral metabolites, including macromolecules (MMs) and lipids. Data were transferred from the MRS scanners to a workstation, and metabolites were quantified with the spectrogram-based eddy current method and water scaling.MM levels were significantly higher in patients with a slow gait and executive dysfunction due to normal pressure hydrocephalus (NPH) than in asymptomatic volunteers (p <0.01). In contrast, the N-acetyl aspartate (NAA) level was significantly lower in patients with executive dysfunction than in asymptomatic volunteers (p <0.01). There were no statistically significant differences in metabolites, including alanine, aspartate, creatine, γ-amino butyric acid, D-glucose, glutamine, glutamate, glycerophosphorylcholine, phosphorylcholine, lactate, myoinositol, N-acetyl-aspartyl-glutamate, scyllo-inositol, taurine, creatine methylene, and guanine, in the centrum semiovale between patients with NPH and asymptomatic volunteers.We quantitatively evaluated cerebral metabolites, particularly in the centrum semiovale, with MRS. In the brain of patients with a slow gait and executive dysfunction due to NPH, MRS revealed significantly higher MM levels and lower NAA levels compared to healthy volunteers. Therefore, it may be concluded that the patients have a dysfunctional glymphatic system in the brain.

Streptococcus oralis Meningitis with Gingival Bleeding in a Patient: A Case Report and Review of the Literature.

An 81-year-old man with a history of gingival bleeding presented with a fever, headache, and drowsiness. His mouth and full dentures were unsanitary. Laboratory tests revealed Streptococcus oralis meningitis caused by odontogenic bacteremia. We reviewed eight reported cases, including the present case, because S. oralis meningitis is rare. Our review indicated that S. oralis meningitis needs to be considered when encountering cases of a fever, disturbance of consciousness, and headache with episodes of possible odontogenic bacteremia.

Natural Y-shaped radial artery graft bypass for a complex middle cerebral artery aneurysm: A case report.

Giant thrombosed middle cerebral artery (MCA) aneurysms are difficult to treat and sometimes require complex revascularization using allografts. We describe a technical method using revascularization with a natural Y-shaped graft that provides a normal variation for a complex MCA aneurysm. A 65-year-old man with a giant thrombosed MCA aneurysm presented with right hemiparesis and aphasia. The patient had a history of clipping surgery for the ipsilateral side of the MCA aneurysm 25 years before, and a de novo aneurysm developed over the previous 18 years. For the giant thrombosed aneurysm, trapping and revascularization were performed. A natural radial artery Y-graft was used as the graft and anastomosed to both M2 trunks. The symptoms improved after surgery, and the patient was discharged 3 weeks later. This is the first report of a double-barrel bypass using a natural Y-graft. This method attained a normal variation, and the flow of the Y-graft was physiological. For the radical cure of giant thrombosed MCA aneurysms, multiple revascularizations might be required. With this natural Y-graft, complex transpositions could be avoided.

Ischemic Tolerance Evaluated by Computed Tomography Perfusion during Balloon Test Occlusion.

OBJECTIVES: Balloon test occlusion (BTO) is performed to evaluate ischemic tolerance for large and giant cerebral aneurysms and head and neck tumors that may require parent artery occlusion. However, ischemic tolerance for the temporary test occlusion does not always guarantee a tolerance for permanent occlusion. In this study, we evaluated the utility of computed tomography (CT) perfusion during BTO to quantify ischemic tolerance for detecting delayed ischemic stroke. MATERIALS AND METHODS: Forty-one patients who underwent BTO for the internal carotid artery were included. The correlations between the parameters of CT perfusion and collateral angiographic appearance or stump pressure during BTO were evaluated. The cerebral blood flow (CBF), cerebral blood volume, mean transit time (MTT), and time to peak (TTP) were obtained through CT perfusion, and the asymmetry ratios were determined. Collateral angiographic appearances were categorized into 5 grades (0-4). RESULTS: The collateral angiographic appearance showed moderate correlations with CBF, MTT, and TTP that was significant. Of these, the absolute value of the correlation coefficient was the highest for MTT. MTT also showed a moderate correlation with stump pressure. CBF and MTT were significantly different between the poor collateral group (grades 2 and 3) and the good collateral group (grade 4). Based on the MTT, the good collateral group was identified with high sensitivity (75.0%) and specificity (81.2%). CONCLUSIONS: In BTO, the MTT obtained through CT perfusion showed a correlation with collateral angiographic appearance and stump pressure. Thus, the MTT might be useful to quantify ischemic tolerance for detecting delayed ischemic stroke.

Morelloflavone as a novel inhibitor of mitotic kinesin Eg5.

Among 40 plant-derived biflavonoids with inhibitory potential against Eg5, morelloflavone from Garcinia dulcis leaves was selected for further testing based on in silico analysis of binding modes, molecular interactions, binding energies and functional groups that interact with Eg5. Computational models predicted that morelloflavone binds the putative allosteric pocket of Eg5, within the cavity surrounded by amino acid residues of Ile-136, Glu-116, Glu-118, Trp-127, Gly-117, Ala-133, Glu-215, Leu-214 and Tyr-211. Binding energy was -8.4 kcal/mol, with a single hydrogen bond formed between morelloflavone and Tyr-211. The binding configuration was comparable to that of a reference inhibitor, S-trityl-L-cysteine. Subsequent biochemical analysis in vitro confirmed that morelloflavone inhibited both the basal and microtubule-activated ATPase activity of Eg5 in a manner that does not compete with ATP binding. Morelloflavone also suppressed Eg5 gliding along microtubules. These results suggest that morelloflavone binds the allosteric binding site in Eg5 and thereby inhibits ATPase activity and motor function of Eg5.