Multiple Synchronous Spinal Dural Arteriovenous Fistulas: A Systematic Literature Review.

BACKGROUND AND OBJECTIVES: Spinal dural arteriovenous fistulas (SDAVFs) lead to progressive neurological decline with symptoms such as paraparesis, bowel and bladder dysfunction, and sensory disturbances because of impaired spinal cord venous drainage. This study aimed to systematically review the literature on multiple synchronous SDAVFs and present 2 cases from our institution. METHODS: A comprehensive search was performed to identify all published cases of multiple synchronous SDAVFs. Overall, 23 patients with multiple synchronous SDAVFs were identified, including 21 from 19 articles and 2 from this study. The clinical presentation, lesion location, radiographic features, surgical treatment, and outcomes were analyzed in each patient. RESULTS: All patients in this study were male, and the duration from symptom onset to diagnosis in many of these patients was longer than that previously reported. Previous studies suggested that multiple SDAVFs typically occurred within 3 or fewer vertebral levels. However, >50% of the examined patients had remote lesions separated by more than 3 vertebral levels. Patients with remote lesions had a significantly worse outcome (1/7 vs 8/11, 95% CI 0.001-0.998; P = .049). CONCLUSION: Accurately locating fistulas before spinal angiography is critical for managing multiple remote SDAVFs. Considering the possibility of multiple remote SDAVFs, careful interpretation of imaging findings is essential for an accurate diagnosis and appropriate treatment planning.

A vertebrobasilar junction aneurysm successfully treated with a combination of surgical clipping and flow diverter placement based on the results of computational fluid dynamics analysis: illustrative case.

BACKGROUND: The treatment of vertebrobasilar junction (VBJ) aneurysms is challenging. Although flow diverters (FDs) are a possible treatment option, geometrical conditions hinder intervention. VBJ aneurysms possess dual inflow vessels from the bilateral vertebral arteries (VAs), one of which is ideally occluded prior to FD treatment. However, it remains unclear which VA should be occluded. OBSERVATIONS: A 75-year-old male with a growing VBJ complex aneurysm exhibiting invagination toward the brainstem and causing perifocal edema required intervention. Preoperative computational fluid dynamics (CFD) analysis demonstrated that left VA occlusion would result in more stagnant flow and less impingement of flow than right VA occlusion. According to the simulated strategy, surgical clipping of the left VA just proximal to the aneurysm was performed, followed by FD placement from the basilar artery trunk to the right VA. The patient demonstrated tolerance of the VA occlusion, and follow-up computed tomography angiography at 18 months after FD treatment confirmed the disappearance of the aneurysm. LESSONS: Preoperative flow dynamics simulations using CFD analysis can reveal an optimal treatment strategy involving a hybrid surgery that combines FD placement and direct surgical occlusion for a VBJ complex aneurysm.

Combined transarterial and transvenous embolization of anterior cranial fossa dural arteriovenous fistula.

Background: Excessive glue injection into the drainage vein in patients with dural arteriovenous fistula (dAVF) can result in venous obstruction. We performed transarterial embolization (TAE) combined with transvenous embolization (TVE) with coils to prevent the glue from migrating into the normal cortical veins. Case Description: A 57-year-old man was pointed out to have a Borden Type III anterior cranial fossa dAVF during a check-up for putaminal hemorrhage. Because a left frontal normal cortical vein drained into the pathological drainage vein, excessive glue injection into the drainage vein may have caused venous obstruction. We performed TVE with coils at the foot of the draining vein to prevent excessive migration of glue into the drainer, followed by TAE with glue. With this technique, complete obliteration of the shunt without venous ischemia was obtained. Conclusion: The combined treatment of TAE and TVE is effective in preventing venous ischemia caused by unintended migration of glue cast into the drainage vein.

Effects of carotid revascularization on cognitive function and brain functional connectivity in carotid stenosis patients with cognitive impairment: a pilot study.

OBJECTIVE: Carotid stenosis can lead to both cognitive impairment (CI) and ischemic stroke. Although carotid revascularization surgery, which includes carotid endarterectomy (CEA) and carotid artery stenting (CAS), can prevent future strokes, its effect on cognitive function is controversial. In this study, the authors examined resting-state functional connectivity (FC) in carotid stenosis patients with CI undergoing revascularization surgery, with a particular focus on the default mode network (DMN). METHODS: Twenty-seven patients with carotid stenosis who were scheduled to undergo CEA or CAS between April 2016 and December 2020 were prospectively enrolled. A cognitive assessment, including the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Japanese version of the Montreal Cognitive Assessment (MoCA), as well as resting-state functional MRI, was performed 1 week preoperatively and 3 months postoperatively. For FC analysis, a seed was placed in the region associated with the DMN. The patients were divided into two groups according to the preoperative MoCA score: a normal cognition (NC) group (MoCA score ≥ 26) and a CI group (MoCA score < 26). The difference in cognitive function and FC between the NC and CI groups was investigated first, and then the change in cognitive function and FC after carotid revascularization was investigated in the CI group. RESULTS: There were 11 and 16 patients in the NC and CI groups, respectively. The FC of the medial prefrontal cortex with the precuneus and that of the left lateral parietal cortex (LLP) with the right cerebellum were significantly lower in the CI group than in the NC group. In the CI group, significant improvements were found in MMSE (25.3 vs 26.8, p = 0.02), FAB (14.4 vs 15.6, p = 0.01), and MoCA scores (20.1 vs 23.9, p = 0.0001) after revascularization surgery. Significantly increased FC of the LLP with the right intracalcarine cortex, right lingual gyrus, and precuneus was observed after carotid revascularization. In addition, there was a significant positive correlation between the increased FC of the LLP with the precuneus and improvement in the MoCA score after carotid revascularization. CONCLUSIONS: These findings suggest that carotid revascularization, including CEA and CAS, might improve cognitive function based on brain FC in the DMN in carotid stenosis patients with CI.

Endovascular Treatment of Borden Type III Transverse-sigmoid Sinus Dural Arteriovenous Fistulas: a Single-center 12-year Experience.

PURPOSE: The objective of this study was to evaluate our 12-year experience in treating Borden type III transverse-sigmoid sinus (TSS) dural arteriovenous fistulas (DAVFs) and discuss the technical aspects of ipsilateral and contralateral transvenous embolization (TVE) approaches. METHODS: We retrospectively reviewed charts of consecutive patients with TSS DAVF treated with multimodal treatment between April 2008 and March 2020. The baseline patient characteristics, imaging data, details of procedure, data sets of sinus pressure monitoring, and clinical results were systematically collected. RESULTS: Of 44 patients with TSS DAVF who were treated during study periods, 23 patients of Borden type III were extracted. Among the 23 patients, 18 with transfemoral TVE were included for analysis. TVE was performed using an ipsilateral approach in 8 patients and a contralateral approach in 10. Pressure monitoring data revealed that initial mean sinus pressure (43.5 mmHg vs. 29.5 mmHg; P = 0.033), maximum sinus pressure during the procedure (69.0 mmHg vs. 40.5 mmHg; P = 0.011), and sinus pressure gradient (22.5 mmHg vs. 5.5 mmHg; P = 0.021) were significantly higher in the ipsilateral approach group. The complete obliteration rate by primary embolization was 94% in our cohort with the recurrence rate of 5.6% with a median follow-up period of 57 months. CONCLUSION: Our study showed the durability of TVE for patients with Borden type III TSS DAVF. TVE performed via the contralateral approach might prevent a potentially dangerous increase in intraprocedural sinus pressure and cortical venous reflux.

Spinal cord infarction after coil embolization of a basilar tip aneurysm: A case report and literature review.

Background: Spinal cord infarction is a rare but serious complication of neurointervention that has been rarely documented. An association between spinal cord infarction and the placement of large bore catheters in the vertebral artery (VA) has been mentioned, but the precise etiology remains unclear. Case Description: A 72-year-old female presented with the right hemiparesis and left thermal hypoalgesia directly after endovascular coil embolization for an unruptured basilar tip aneurysm. Magnetic resonance imaging demonstrated right-sided upper cervical (C2-3) spinal cord infarction. Conventional bilateral vertebral angiograms revealed no opacification of the anterior spinal arteries. Cone-beam computed tomography showed a watershed area of radiculomedullary arteries that was correlated with the extent of the ischemic lesion. Thus, the spinal cord ischemia may have had multifactorial causes combined with reduced perfusion pressure to the spinal cord, which was caused by the placement of the guiding catheter in the VA and intensive hypotension during general anesthesia. Conclusion: Spinal cord infarction should be recognized as a serious complication of endovascular treatment involving posterior circulation.

Glutamic Acid and Total Creatine as Predictive Markers for Epilepsy in Glioblastoma by Using Magnetic Resonance Spectroscopy Before Surgery.

OBJECTIVE: Epilepsy in glioblastoma patients significantly reduces their quality of life; however, little is known about the association between predicting epilepsy and metabolites in tumors. In this study, we used 3.0-T magnetic resonance imaging and 1H-magnetic resonance spectroscopy (MRS) to quantify metabolite concentrations in patients with varying epilepsy histories. METHODS: Fifty-one patients with glioblastoma underwent pretreatment 3.0-T MRI/1H-MRS scanning. Single-voxel (1.5 cm3) MRS, in an enhanced lesion, was acquired using a double-echo point-resolved spectroscopic sequence with chemical-shift selective water suppression. MRS data were quantified with linear combination model (LC-Model) software. We compared the MRS data between groups with and without epilepsy during the postoperative course (EP). RESULTS: The ratios of glutamate (Glu) and glutamate + glutamine (Glx) to total creatine (Glu/tCr and Glx/tCr) in the tumor were associated with epilepsy history. The receiver operating characteristic curve analysis showed that a Glu/tCr value of 1.81 was 70% sensitive and 90% specific for the prediction of EP (area under curve: 0.82). In the analysis excluding patients with preoperative epilepsy, a Glu/tCr value of 1.81 was 75% sensitive and 88% specific for the prediction (area under curve: 0.87). CONCLUSIONS: Intratumoral metabolite concentrations measured using pretreatment 3.0-T MRI/1H-MRS changed characteristically in the group with EP. Our study suggests that the Glu/tCr ratio in tumors has adequate reliability in predicting EP. Pretreatment MRS is a minimally invasive and simple procedure that can provide useful information on glioblastoma patients.

Potential of machine learning to predict early ischemic events after carotid endarterectomy or stenting: a comparison with surgeon predictions.

Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are recommended for high stroke-risk patients with carotid artery stenosis to reduce ischemic events. However, we often face difficulty in determining the best treatment strategy. We aimed to develop an accurate post-CEA/CAS outcome prediction model using machine learning that will serve as a basis for a new decision support tool for patient-specific treatment planning. Retrospectively collected data from 165 consecutive patients with carotid stenosis underwent CEA or CAS and were divided into training and test samples. The following five machine learning algorithms were tuned, and their predictive performance was evaluated by comparison with surgeon predictions: an artificial neural network, logistic regression, support vector machine, random forest, and extreme gradient boosting (XGBoost). Seventeen clinical factors were introduced into the models. Outcome was defined as any ischemic stroke within 30 days after treatment including asymptomatic diffusion-weighted imaging abnormalities. The XGBoost model performed the best in the evaluation; its sensitivity, specificity, positive predictive value, and accuracy were 31.9%, 94.6%, 47.2%, and 86.2%, respectively. These statistical measures were comparable to those of surgeons. Internal carotid artery peak systolic velocity, low-density lipoprotein cholesterol, and procedure (CEA or CAS) were the most contributing factors according to the XGBoost algorithm. We were able to develop a post-procedural outcome prediction model comparable to surgeons in performance. The accurate outcome prediction model will make it possible to make a more appropriate patient-specific selection of CEA or CAS for the treatment of carotid artery stenosis.

Contribution of Endoplasmic Reticulum Stress to the Clinical Instability of Carotid Plaques in Human Carotid Stenosis.

Endoplasmic reticulum (ER) stress is an important process during the progression of atherosclerosis. The aim of this study was to elucidate the association of ER stress and clinical instability of carotid plaque. One hundred ninety-three patients with carotid stenosis undergoing carotid endarterectomies (CEAs) were enrolled. We classified the patients into 3 groups: the asymptomatic, symptomatic, and cTIA (crescendo transient ischemic attack)/SIE (stroke in evolution) groups. Immunohistological staining was performed to assess ER stress and apoptosis. The correlation between ER stress marker expression and clinical instability was analyzed by Tukey-Kramer test and ordinal logistic regression. From the 193 CEAs, 24 asymptomatic plaques and 24 symptomatic plaques were randomly selected, and all 7 plaques in the cTIA/SIE group were selected. Glycophorin A staining demonstrated significant correlation between intraplaque hemorrhage and clinical instability (odds ratio [OR], 1.27; 95%CI, 1.14-1.41). The expression of ER stress markers (glucose-regulated protein 78 [GRP78] and C/EBP homologous protein [CHOP]) exhibited a significant correlation with clinical instability (GRP78: OR, 1.25; 95%CI, 1.14-1.38, CHOP: OR, 1.39; 95%CI, 1.16-1.66). Double-label immunofluorescence demonstrated ER stress markers were detected in CD68-positive cells and smooth muscle actin (SMA)-positive cells. The coexpression of the ER stress markers exhibited a significant correlation with clinical instability (CD68/GRP78: OR, 1.13; 95%CI, 1.05-1.20, CD68/CHOP: OR, 1.092; 95%CI, 1.04-1.14, SMA/CHOP: OR, 1.082; 95%CI, 1.04-1.13). However, the colocalization of CHOP and cleaved caspase-3 (apoptosis marker) did not correlate with clinical instability. These findings indicated that the ER stress pathway may be a potential therapeutic target in the prevention of stroke.

Glioma cells require one-carbon metabolism to survive glutamine starvation.

Cancer cells optimize nutrient utilization to supply energetic and biosynthetic pathways. This metabolic process also includes redox maintenance and epigenetic regulation through nucleic acid and protein methylation, which enhance tumorigenicity and clinical resistance. However, less is known about how cancer cells exhibit metabolic flexibility to sustain cell growth and survival from nutrient starvation. Here, we find that serine and glycine levels were higher in low-nutrient regions of tumors in glioblastoma multiforme (GBM) patients than they were in other regions. Metabolic and functional studies in GBM cells demonstrated that serine availability and one-carbon metabolism support glioma cell survival following glutamine deprivation. Serine synthesis was mediated through autophagy rather than glycolysis. Gene expression analysis identified upregulation of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) to regulate one-carbon metabolism. In clinical samples, MTHFD2 expression was highest in the nutrient-poor areas around "pseudopalisading necrosis." Genetic suppression of MTHFD2 and autophagy inhibition caused tumor cell death and growth inhibition of glioma cells upon glutamine deprivation. These results highlight a critical role for serine-dependent one-carbon metabolism in surviving glutamine starvation and suggest new therapeutic targets for glioma cells adapting to a low-nutrient microenvironment.

Metabolic changes and anti-tumor effects of a ketogenic diet combined with anti-angiogenic therapy in a glioblastoma mouse model.

The ketogenic diet (KD) is a high fat and low carbohydrate diet that produces ketone bodies through imitation of starvation. The combination of KD and Bevacizumab (Bev), a VEGF inhibitor, is considered to further reduce the supply of glucose to the tumor. The metabolite changes in U87 glioblastoma mouse models treated with KD and/or Bev were examined using gas chromatography-mass spectrometry. The combination therapy of KD and Bev showed a decrease in the rate of tumor growth and an increase in the survival time of mice, although KD alone did not have survival benefit. In the metabolome analysis, the pattern of changes for most amino acids are similar between tumor and brain tissues, however, some amino acids such as aspartic acid and glutamic acid were different between tumors and brain tissues. The KD enhanced the anti-tumor efficacy of Bev in a glioblastoma intracranial implantation mouse model, based on lowest levels of microvascular density (CD31) and cellular proliferation markers (Ki-67 and CCND1) in KD + Bev tumors compared to the other groups. These results suggested that KD combined with Bev may be a useful treatment strategy for patients with GBM.

Impact of transvenous embolization via superior ophthalmic vein on reducing the total number of coils used for patients with cavernous sinus dural arteriovenous fistula.

Although transvenous embolization (TVE) via the superior ophthalmic vein (SOV) is adopted in treating cavernous sinus dural arteriovenous fistula (CS DAVF), its effect on the coil volume is rarely understood. The purpose of the study was to investigate if there is a difference in the total number of coils used and in patient safety when comparing two access strategies. We retrospectively reviewed charts for patients with CS DAVF treated with TVE between January 2008 and March 2018. The baseline patient characteristics, details of procedure, placed coils, and clinical results were compared. A total of 42 patients with CS DAVF were treated with the inferior petrosal sinus (IPS) (n = 32) or SOV (n = 10) approach. TVE via SOV showed a high success rate of 100% (10/10) by transfemoral access. The total number (23 versus 11; P < 0.001), length (159 versus 81 cm; P = 0.003), and volume of placed coils (111 versus 46 mm3; P = 0.005) were significantly lower in patients treated via SOV. Patients treated via SOV had significantly higher initial intrasinus pressure (49 versus 59 mmHg; P = 0.022) obtained by microcatheters; however, no adverse events occurred related to elevated sinus pressure between both approaches. Procedural complications and cranial nerve palsy outcomes were not significantly different. In cases with a visualized pathway to the SOV, this approach should be preferred, in all other cases standard approach via the IPS should be used, even if it cannot be visualized.

Endovascular Internal Trapping by Low-Concentration N-butyl-2-Cyanoacrylate for a Ruptured Giant Common Carotid Artery Pseudoaneurysm.

Treating carotid blowout syndrome following rupture of giant pseudoaneurysms is difficult because the destroyed parent artery precludes conventional treatment. We present a patient with a ruptured giant pseudoaneurysm that we occluded using a modified internal trapping technique with low-concentration N-butyl-2-cyanoacrylate (NBCA) and a minimum number of coils. An 80-year-old man with a history of chemoradiation therapy for oropharyngeal cancer presented with several episodes of active bleeding from the subsequent tracheostomy site. Radiological examination revealed a giant right common carotid artery (CCA) pseudoaneurysm. Endovascular internal trapping was performed using both NBCA and coils under proximal flow control. We slowly injected 9 ml of low-concentration NBCA, which subsequently filled the entire pseudoaneurysm. We then injected an additional 2 ml of NBCA into the proximal CCA to achieve complete obliteration. No re-bleeding was observed during the 6-month follow-up. Endovascular internal trapping using low-concentration NBCA was feasible to treat a giant CCA pseudoaneurysm. The injected low-concentration NBCA filled the entire pseudoaneurysm without the risk of catheter entrapment.

Successful Double-Catheter Coil Embolization of an Iatrogenic Subclavian Artery to Internal Jugular Vein Fistula After Minimally Invasive Cardiac Surgery.

It is essential to establish cardiopulmonary bypass by percutaneous insertion of a large-bore catheter via both the femoral vein and internal jugular vein (IJV) for minimally invasive cardiac surgery (MICS). Complications associated with IJV catheterization during MICS have been reported in the literature; however, vascular injury of the subclavian artery (SCA) is rare. We herein present a rare case in which an iatrogenic arteriovenous fistula (AVF) between the right SCA and IJV after MICS was successfully treated by endovascular coil embolization. A 61-year-old man who had undergone mitral valve repair by MICS 10 months before presentation was referred because of pulsatile cervical bruit and tinnitus. Radiographic examination revealed a right SCA pseudoaneurysm associated with an AVF located between the right common carotid artery and vertebral artery. The AVF was completely occluded with detachable coils using a double-catheter technique to avoid coil migration into the IJV. This technique has been used to treat high-flow or complex AVFs, including pulmonary and renal AVFs. As shown in the present case, it is also useful to treat an iatrogenic AVF between the SCA and IJV.

Multi-marker algorithms based on CXCL13, IL-10, sIL-2 receptor, and ß2-microglobulin in cerebrospinal fluid to diagnose CNS lymphoma.

Tumor biopsy is essential for the definitive diagnosis of central nervous system (CNS) lymphoma. However, the biopsy procedure carries the risk of complications such as bleeding, convulsions, and infection. Cerebrospinal fluid (CSF) ß2-microglobulin (ß2-MG), soluble IL-2 receptor (sIL-2R), and interleukin-10 (IL-10) are known to be useful diagnostic biomarkers for CNS lymphoma. The C-X-C motif chemokine ligand 13 (CXCL13) was recently reported to be another useful biomarker for CNS lymphoma. The purpose of this study is to establish a diagnostic algorithm that can avoid biopsy by combining these diagnostic biomarkers. In the first, we conducted a case-control study (n = 248) demonstrating that the CSF CXCL13 concentration was significantly increased in CNS lymphoma patients compared with various other brain diseases (AUC = 0.981). We established a multi-marker diagnostic model using CSF CXCL13, IL-10, ß2-MG, and sIL-2R from the results of the case-control study and then applied the model to a prospective study (n = 104) to evaluate its utility. The multi-marker diagnostic algorithms had excellent diagnostic performance: the sensitivity, specificity, positive predictive value, and negative predictive value were 97%, 97%, 94%, and 99%, respectively. In addition, CSF CXCL13 was a prognostic biomarker for CNS lymphoma patients. Our study suggests that multi-marker algorithms are important diagnostic tools for patients with CNS lymphoma.

Ultrasonographically-guided stent placement at the vertebral artery origin without contrast medium: A case report.

Although ultrasonographically-guided carotid interventions without contrast medium have been reported in the literature, we found no report regarding stenting of the vertebral artery origin for treatment of stenosis. Here, we report the case of an iodine-allergic patient in whom a stenosis at the origin of the vertebral artery was successfully treated with ultrasonographically-guided stent placement without contrast medium. B-mode longitudinal images were monitored during the insertion of the embolism-protection device, when positioning the stent, and for the evaluation of the stent opening. This technique can be an alternative option in selected patients, especially those allergic to the contrast medium.

Microcatheter injection reduces the amount of contrast medium during middle cerebral artery aneurysm embolization in a patient with chronic kidney disease.

We describe a unique technique to reduce the amount of contrast medium by injecting diluted contrast medium from the microcatheter during neurointervention. A patient with severe renal impairment due to polycystic kidney was referred for endovascular surgery for wide-neck middle cerebral artery aneurysm. In order to reduce the amount of contrast medium, contrast medium was injected from the microcatheter placed in the middle cerebral artery during coil embolization; renal function decline was not observed after the procedure. This technique, therefore, reduces the amount of contrast medium and enables one to perform coil embolization safely.

Transarterial Onyx embolization with targeted balloon-assisted sinus protection for treatment of dural arteriovenous fistula of the lateral tentorial sinus.

We present a unique sinus protection technique that uses a short-length supercompliant balloon during the transarterial Onyx embolization for the dural arteriovenous fistula (DAVF) of the lateral tentorial sinus. With this technique, we temporarily change the Borden classification from type II to type III, avoiding venous compromise and reducing the risk of Onyx migration into the patent sinus. A 54-year-old man presented with left persistent tinnitus of 4 months' duration. Cerebral angiography revealed a Borden type II left lateral tentorial sinus-DAVF associated with retrograde cortical venous reflux draining into the vein of Labbé. In the venous phase, the ipsilateral transverse-sigmoid sinus was recognized as a functional sinus and the posterior temporal vein drained into the transverse sinus near the drainage channel. We planned to perform transarterial Onyx embolization using a short-length sinus protection balloon to protect against Onyx migration. During transarterial Onyx injection, a 7 × 7-mm HyperForm balloon was navigated into the affected sinus and positioned to cover the drainage channel from the shunt. After confirming the change in Borden classification with angiography, transarterial Onyx embolization was performed via the middle meningeal artery. This procedure resulted in complete obliteration of the fistula with good patency of both the transverse-sigmoid sinus and neighboring normal cortical veins. No procedure-related complications were observed and the patient remained free of recurrence during the 24-month follow-up period. Short-length balloon-protected Onyx embolization can be safe and effective for the treatment of Borden type II DAVF.