OBJECT Convection-enhanced delivery (CED) is an effective drug delivery method that delivers high concentrations of drugs directly into the targeted lesion beyond the blood-brain barrier. However, the drug distribution attained using CED has not satisfactorily covered the entire targeted lesion in tumors such as glioma. Recently, the efficacy of ultrasound assistance was reported for various drug delivery applications. The authors developed a new ultrasound-facilitated drug delivery (UFD) system that enables the application of ultrasound at the infusion site. The purpose of this study was to demonstrate the efficacy of the UFD system and to examine effective ultrasound profiles. METHODS The authors fabricated a steel bar-based device that generates ultrasound and enables infusion of the aqueous drug from one end of the bar. The volume of distribution (Vd) after infusion of 10 ml of 2% Evans blue dye (EBD) into rodent brain was tested with different frequencies and applied voltages: 252 kHz/30 V; 252 kHz/60 V; 524 kHz/13 V; 524 kHz/30 V; and 524 kHz/60 V. In addition, infusion of 5 mM gadopentetate dimeglumine (Gd-DTPA) was tested with 260 kHz/60 V, the distribution of which was evaluated using a 7-T MRI unit. In a nonhuman primate (Macaca fascicularis) study, 300 μl of 1 mM Gd-DTPA/EBD was infused. The final distribution was evaluated using MRI. Two-sample comparisons were made by Student t-test, and 1-way ANOVA was used for multiple comparisons. Significance was set at p < 0.05. RESULTS After infusion of 10 μl of EBD into the rat brain using the UFD system, the Vds of EBD in the UFD groups were significantly larger than those of the control group. When a frequency of 252 kHz was applied, the Vd of the group in which 60 V was applied was significantly larger than that of the group in which 30 V was used. When a frequency of 524 kHz was applied, the Vd tended to increase with application of a higher voltage; however, the differences were not significant (1-way ANOVA). The Vd of Gd-DTPA was also significantly larger in the UFD group than in the control group (p < 0.05, Student t-test). The volume of Gd-DTPA in the nonhuman primate used in this study was 1209.8 ± 193.6 mm(3). This volume was much larger than that achieved by conventional CED (568.6 ± 141.0 mm(3)). CONCLUSIONS The UFD system facilitated the distribution of EBD and Gd-DTPA more effectively than conventional CED. Lower frequency and higher applied voltage using resonance frequencies might be more effective to enlarge the Vd. The UFD system may provide a new treatment approach for CNS disorders.

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Expression of CD44 in glioma cells was previously correlated with tumor grade and is considered a stem cell marker. CD44 stabilizes the cystine-glutamate transporter (xCT) and inhibits apoptosis in cancer stem cells (CSCs). Recently it was found that Sulfasalazine (SSZ), an anti-inflammatory drug, acts as an inhibitor of xCT and therefore has potential as a targeted therapy for CSCs. In this study, we tested an efficacy of SSZ against glioma stem cell model developed in rats. As poor penetration of blood-brain barrier resulted in insufficient efficacy of systemic SSZ treatment, SSZ was delivered locally with convection-enhanced delivery (CED). In vitro, expression of CD44 in glioma cells and efficacy of SSZ against glioma cells and glioma stem cells were confirmed. SSZ demonstrated anti-proliferative activity in a dose dependent manner against these cells. This activity was partially reversible with the addition of antioxidant, N-acetyl-L-cysteine, to the medium. In vivo, CED successfully delivered SSZ into the rat brain parenchyma. When delivered at 5 mM concentration, which was the highest possible concentration when SSZ was dissolved in water, CED of SSZ resulted in almost no tissue damage. Against highly malignant bRiTs-G3 brain tumor xenografted rat model; the glioma stem cell model, CED of SSZ at 5 mM concentration induced apoptosis and prolonged survival. Consequently, CED of SSZ induced glioma stem cell death without evidence of tissue damage to normal brain parenchyma. This strategy may be a promising targeted treatment against glioma stem cells.

In Cognard type V DAVS, anterior venous drainage is dominant. Because the anterior spinal veins are located subpially, flow voids are less prominent on sagittal T2-weighted MRI. This may lead to difficulties in diagnosing. Evaluation with MR angiography may compensate for these limitations.

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Fenestration of the supraclinoid internal carotid artery (ICA) is extremely rare and may occasionally be associated with saccular aneurysms; nevertheless, the natural history remains unclear. The authors reviewed the cases of fenestration of the supraclinoid ICA and evaluated the clinical characteristics and angioarchitecture with particular focus on the incidence for aneurysm development and rupture. Previously reported 24 cases and 1 new case from our institute were examined for the presence of aneurysms (including size and presence of bleb) leading to subsequent subarachnoid hemorrhage (SAH). Furthermore, 16 cases with sufficient information were classified into one of the three types according to the developmental condition of fenestration and fusion site: Type A (developed fenestration in which the ICA appears to duplicate [two cases]); Type B (hypoplastic fenestration fused to the ICA at the origin of the posterior communicating artery [Pcom] [six cases]); and Type C (hypoplastic fenestration fused to the Pcom itself or appeared to be a duplicated Pcom [eight cases]). In type A, the two cases had an aneurysm (100%), one of which caused SAH (50%). In type B, all six cases had an aneurysm (100%), and one of five led to SAH (20%) (one case lacked information regarding SAH). In type C, five of the eight cases had an aneurysm (62.5%), with no SAH (0%). The result suggested that the extent of development of fenestration and the location of fusion are related to the incidence of aneurysms and risk for rupture.

Introduction Sturge–Weber syndrome (SWS) is a rare congenital disease that affects the brain, skin, and eyes, and is a sporadically occurring neurocutaneous syndrome that affects intracerebral veins, which is associated with venous thrombosis. However, intracranial hemorrhage in patients with SWS is rare. We herein report a rare case of SWS with intracerebral hemorrhage derived from sinus thrombosis.Case descriptionA 62-year-old man suddenly fell into a coma and was admitted to our hospital. His neurological status was assessed as GCS 6 (E1V1M4) with right-sided hemiparesis. At birth, he had a right-sided facial port-wine stain typical of SWS that involved the ophthalmic division of the trigeminal nerve. Laboratory findings showed that he was dehydrated, and his serum D-dimer concentration was increased. Computed tomography revealed left thalamic hemorrhage with acute hydrocephalus and cortical calcification in the right occipital lobe. Magnetic resonance imaging displayed a vascular malformation of the right cerebral hemisphere consistent with SWS. Magnetic resonance venography showed steno-occlusion of the superior sagittal sinus, straight sinus, and left internal cerebral vein (ICV). Emergency ventricular drainage was performed. Seven days after surgery, his consciousness improved to GCS 14 (E4V4M6). Rehydration therapy was performed to prevent sinus thrombosis.Discussion and EvaluationHis postoperative course was uneventful. Sudden congestion of the left ICV may have caused left thalamic hemorrhage.ConclusionsSWS with major sinus occlusion needs to be diagnosed with utmost caution in order to allow for preoperative neurological and radiological assessments.

A 55-year-old man with an 8-year history of invasive thymoma presented with sudden onset of left hemiparesis. Computed tomography (CT) and magnetic resonance (MR) imaging showed a right frontal lobe intracerebral hemorrhage and the possibility of brain metastasis could not be rejected. The patient underwent removal of the hematoma. Histological examination showed brain metastasis from invasive thymoma. To the best of our knowledge, this is the fi rst reported case of hemorrhagic brain metastasis from invasive thymoma (non-cancerous) mimicking intracerebral hemorrhage.