Convection-enhanced delivery of sulfasalazine prolongs survival in a glioma stem cell brain tumor model.

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.

Endovascular Treatment of Wide-Neck Bifurcation Aneurysm: Recent Trends in Coil Embolization with Adjunctive Technique.

Wide-neck bifurcation aneurysms (WNBAs) are sometimes challenging to treat. During endovascular treatment, it is important to prevent coil deviation and preserve normal vessels. Adjunctive balloon- and stent-assisted techniques have been developed. A meta-analysis of endovascular treatments of WNBAs revealed that only 40% of patients had complete occlusion. Recently, novel devices have been developed to expand the range of treatment options. Flow-diverter stents and intra-aneurysmal flow disruption devices do not require coils; however, coil embolization remains the standard procedure used by many neurointerventionists. This review describes the recent trends in adjunctive techniques for supporting coil embolization for WNBAs. We referred to literature on balloon-assisted techniques, stent-assisted techniques, Y-stenting, PulseRider, Barrel stents, Comaneci temporary stents, pCONUS, and eCLIPs. These reports showed that adequate embolization rates were generally greater than 80%, and the complete occlusion rate was as high as 94.6%. All devices had a relatively high occlusion rate; however, it may be inaccurate to simply compare each device because of the heterogeneity of the studies. It is important to select the best treatment for each individual case by considering not only literature-based efficacy and safety but also patient background, aneurysm characteristics, and operator experience.

Prophylactic management of cerebral vasospasm with clazosentan in real clinical practice: a single-center retrospective cohort study.

Introduction: Clazosentan, a selective endothelin receptor subtype A antagonist, reduces vasospasm-related morbidity and all-cause mortality following aneurysmal subarachnoid hemorrhage (SAH) in the Japanese population, as demonstrated by a recent randomized phase 3 trial. However, evidence to suggest clazosentan should be prioritized over the current standard of care to prevent cerebral vasospasm is still lacking. Therefore, we investigated the efficacy and safety of clazosentan in comparison with conventional postoperative management in real-world clinical practice. Methods: We conducted a single-center, retrospective, observational cohort study using prospectively collected data from consecutive patients with aneurysmal SAH. After clazosentan was approved for use in Japan, the conventional postoperative management protocol, composed of intravenous fasudil chloride and oral cilostazol (control group, April 2021 to March 2022), was changed to the clazosentan protocol (clazosentan group, April 2022 to March 2023). The primary endpoint was the incidence of vasospasm-related symptomatic infarction. The secondary endpoints were favorable functional outcomes (modified Rankin scale score < 3) at discharge, angiographic vasospasm, and the need for rescue therapy for delayed cerebral ischemia. Results: The analysis included 100 and 81 patients in the control and clazosentan groups, respectively. The incidence of vasospasm-related symptomatic infarction was significantly lower in the clazosentan group than in the control group (6.2% vs. 16%, p = 0.032). Multiple logistic analyses demonstrated that the use of clazosentan was independently associated with fewer incidence of vasospasm-related symptomatic infarct (23.8% vs. 47.5%, odds ratio 0.34 [0.12-0.97], p = 0.032). Clazosentan was significantly associated with favorable outcomes at discharge (79% vs. 66%, p = 0.037). Moreover, both the incidence of angiographic vasospasm (25.9% vs. 44%, p = 0.013) and the need for rescue therapy (16.1% vs. 34%, p = 0.006) was lower in the clazosentan group. The occurrence of pulmonary edema was significantly higher with clazosentan use (19.8% vs. 5%, p = 0.002), which did not result in morbidity. Conclusion: A postoperative management protocol centering on clazosentan was associated with the reduced vasospasm-related symptomatic infarction and improved clinical outcomes compared to the conventional management protocol in Japanese clinical practice. Clazosentan might be a promising treatment option for counteracting cerebral vasospasm after aneurysmal SAH.

Usefulness of Transcranial Motor Evoked Potential in Clipping Surgery for Cerebral Aneurysms-Introduction of a New Protocol for Stable Monitoring.

The usefulness of transcranial motor evoked potentials (Tc-MEPs) in clipping surgery has been reported. However, numerous false positive and false negative cases were reported. We report the usefulness of a new protocol compared with direct cortical MEP (Dc-MEP).Materials were 351 patients who underwent aneurysmal clipping under simultaneous monitoring of Tc- and Dc-MEPs. A total of 337 patients without hemiparesis and 14 with hemiparesis were separately analyzed. Intraoperative changes of Tc-MEP thresholds were examined in the first 50 patients without hemiparesis. The stimulation strength of Tc-MEP was set at +20% of the stimulation threshold. As thresholds changed intraoperatively, thresholds were examined every 10 min and changed stimulation strength.Stimulation thresholds of Tc-MEP were significantly decreased after craniotomy and significantly increased after CSF aspiration. The recording ratios of Tc- and Dc-MEPs were 98.8% and 90.5%, respectively. Out of 304 patients without MEP change, 5 patients developed transient or mild hemiparesis with infarction of the territory of the perforating artery arising from the posterior communicating artery. Out of 31 patients whose MEP transiently disappeared, 3 patients developed transient or mild hemiparesis. The other two patients without MEP recovery manifested persistent hemiparesis. In 14 patients with preoperative hemiparesis, 3 patients whose healthy/affected ratio of Tc-MEP was large developed severe persistent hemiparesis.We clarified the intraoperative changes of Tc-MEP thresholds for the first time. A new protocol of Tc-MEP that followed thresholds and changed stimulation strength to +20% of thresholds is useful for stable monitoring. The usefulness of Tc-MEP is the same as that or better than that of Dc-MEP.

Unusual case of persistent primitive hypoglossal artery with anterior choroidal artery aneurysm in Chiari type I malformation.

Persistent primitive hypoglossal artery (PPHA) is a rare form of persistent embryonic carotid-basilar anastomosis. We present an unusual case of PPHA and an anterior choroidal artery (AChoA) aneurysm associated with Chiari type I malformation. A 45-year-old woman presented with transient dizziness. Magnetic resonance imaging revealed Chiari type I malformation and a left AChoA aneurysm. Digital subtraction angiography incidentally revealed a left PPHA. To the best of our knowledge, this is the first reported case of Chiari malformation in conjunction with PPHA and aneurysms. In this case, the perfusion of the posterior circulation is completely dependent on PPHA. It is very important to identify such variant vessels and complex angioarchitecture before planning neuroendovascular or surgical intervention to prevent possible risks.

Supraclinoid Internal Carotid Artery Fenestration with Associated Aneurysm: Case Report and Literature Review.

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.

Case of Clear Cell Ependymoma Successfully Treated with Preoperative Embolization.

Objective: Clear cell ependymoma (CCE) is known to be very similar to hemangioblastoma (HB) in regards to neuroimaging and histopathology. We report a rare case of CCE in which successfully underwent preoperative embolization with a prior diagnosis of HB. Case Presentation: A 58-year-old woman presented with vertigo for several months. MRI showed the right cerebellar tumor mimicking solid HB. DSA revealed the hypervascular tumor supplied by branches of the posterior inferior cerebellar artery (PICA). To reduce intraoperative bleeding, preoperative embolization was performed using n-butyl-2-cyanoacrylate (NBCA). A flow-guided microcatheter was guided to the proper feeders, and diluted NBCA was injected. Sufficient devascularization was achieved. The tumor was totally resected with minimal blood loss the next day. Postoperative pathological diagnosis was CCE. Conclusion: This is the first report that preoperative embolization was performed to CCE with careful techniques and recent advanced devices. Since CCE has a poorer prognosis, preoperative embolization for safety total resection may be more important.

Growth of Thrombosed Cerebral Venous Varix Following Resection of Cerebral Arteriovenous Malformation: Case Report with Pathologic Consideration.

BACKGROUND: Varix of the drainage route can spontaneously develop thrombosis and disappear after the treatment of the associated cerebral arteriovenous malformation (AVM). We report a rare case in which a thrombosed cerebral venous varix of the drainage route exhibited growth despite complete resection of the associated cerebral AVM. CASE DESCRIPTION: A 46-year-old man was diagnosed with an AVM in the left temporal lobe. The AVM was accompanied by a large venous varix in the superficial venous drainage route. Transarterial embolization was performed followed by resection of the nidus. The venous varix in the drainage route was not resected, as it was buried in the temporal lobe of the dominant hemisphere. The venous varix was ligated using a titanium clip and nylon thread. Postoperative angiography confirmed the disappearance of the AVM, and magnetic resonance imaging showed thrombosis of the venous varix. However, follow-up magnetic resonance imaging performed 5 months after surgery showed the enlargement of the thrombosed venous varix and emergence of perilesional cerebral edema. The venous varix was excised by reoperation to prevent further growth. Histopathologic evaluation showed infiltration of macrophages and multinucleated giant cells and proliferation of capillaries vessels within the walls of the varix, particularly around the embolic and ligation materials. CONCLUSIONS: To the best of our knowledge, this is the first report of the growth of a thrombosed cerebral venous varix after the resection of a cerebral AVM. The possible cause of this rare phenomenon is excessive inflammation with neovascularization within the wall of the venous varix during thrombogenesis, enhanced by reaction against embolic and ligation materials.

Sturge-Weber syndrome with intracerebral hemorrhage: a case report.

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 DESCRIPTION: A 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 EVALUATION: His postoperative course was uneventful. Sudden congestion of the left ICV may have caused left thalamic hemorrhage. CONCLUSIONS: SWS with major sinus occlusion needs to be diagnosed with utmost caution in order to allow for preoperative neurological and radiological assessments.

Intraparenchymal ultrasound application and improved distribution of infusate with convection-enhanced delivery in rodent and nonhuman primate brain.

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.

Rosette-forming Glioneuronal Tumor: Rare Case Presented with Spontaneous Disappearance of Contrast Enhancement.

This report presents rosette-forming glioneuronal tumor (RGNT) of the tectum in a 24-year-old woman in whom spontaneous disappearance of contrast enhancement (CE) on magnetic resonance (MR) imaging was observed during 9-year follow-up period before therapeutic intervention. MR imaging obtained 9 years ago when she first visited local hospital with headaches showed a mass of the brain stem with CE. Follow-up MR imaging showed disappearance of CE without tumor growth. Nine years later, she was admitted to our hospital with headache and nausea, due to obstructive hydrocephalus. She underwent endoscopic third ventriculostomy (ETV) and tumor biopsy. Histological study revealed RGNT. To our knowledge, this is the first report presenting that the RGNT may show spontaneous disappearance of CE without tumor growth. It is unclear what this phenomenon means, however, knowledge of this phenomenon may be helpful for correct diagnosis and for follow up of RGNT.

Subdural empyema due to Lactococcus lactis cremoris: case report.

Lactococcus lactis cremoris (L. lactis cremoris) infections are very rare in humans. Only three case reports of brain abscess have been reported and the infectious routes and pathological features are still unknown. We experienced a subdural empyema due to L. lactis cremoris in an immunocompetent adult. A 33-year-old man was admitted with fever, right facial pain, left hemiparesis, and left hemianopsia. Computed tomography demonstrated low density fluid collection in the right falcotentorial subdural space. Magnetic resonance (MR) images revealed a high signal lesion on a diffusion-weighted image (DWI) and fluid attenuated inversion recovery (FLAIR) images in the right paratentorial and parafalcine subdural space, right maxillary sinus, and bilateral ethmoidal sinus. He underwent two sequential open surgeries for removal and drainage of empyema and was treated with antibiotics including meropenem and ampicillin. To our knowledge, this is the first report of subdural empyema caused by L. lactis cremoris infection. We report the case and discuss the pathological features with the previous literature.

Cognard type V intracranial dural arteriovenous shunt: case reports and literature review with special consideration of the pattern of spinal venous drainage.

BACKGROUND AND IMPORTANCE: Prompt diagnosis of intracranial dural arteriovenous shunt (DAVS) with spinal venous drainage, classified as Cognard type V, is difficult. We investigated the angiographic and magnetic resonance imaging (MRI) characteristics of Cognard type V DAVS to determine the reason for the difficulty in early diagnosis. CLINICAL PRESENTATION: We systematically reviewed 54 published and 3 new cases of Cognard type V DAVS. The pattern of venous drainage was classified on the basis of relative dominance of the anterior and posterior spinal veins with the use of angiograms. T2-weighted sagittal MRIs were used to detect signal flow voids of enlarged spinal veins. Types of venous drainage were determined in 49 of the 57 cases. Twenty-eight and 8 cases showed a dominance of anterior and posterior spinal venous drainage, respectively. In 13 cases, venous drainage was equally distributed through the anterior and posterior spinal veins. Of 41 cases with an abnormally dilated anterior spinal vein, MRIs were available for 25 cases. Signal flow voids of enlarged anterior spinal veins were detected in 9 cases (36.0%), whereas dilatation of the posterior spinal veins was apparent in 9 of 16 cases (56.3%). Overall, MRI detected enlargement of either anterior or posterior spinal veins in 15 of 41 cases (36.6%). CONCLUSION: 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.

Brain metastasis from invasive thymoma mimicking intracerebral hemorrhage: case report.

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 first reported case of hemorrhagic brain metastasis from invasive thymoma (non-cancerous) mimicking intracerebral hemorrhage.

Arachnoid cyst in the middle cranial fossa presenting with pulsatile exophthalmos: case report and literature review.

A 20-year-old woman suffered gradual progression of right pulsatile exophthalmos and slight headache. Computed tomography (CT) demonstrated outward and downward displacement of the right globe and an arachnoid cyst in the right middle cranial fossa associated with thinned and anterior protrusion of a bony orbit. Microscopic cystocisternotomy was performed and the cerebrospinal fluid (CSF) inside of the cyst communicated into the carotid cistern and cistern in the posterior cranial fossa. Pulsatile exophthalmos improved immediately after surgery. Arachnoid cyst in the middle cranial fossa presenting with exophthalmos is rare. Microscopic cystocisternotomy might successfully improve CSF flow and relieve exophthalmos.