[Percutaneous transluminal angioplasty using a stent for an aberrant left subclavian artery stenosis with a right-sided aortic arch: a case report].

An aberrant left subclavian artery is a rare variant that has been reported to coexist with the right-sided aortic arch in many cases. We encountered a case in which percutaneous transluminal angioplasty using a stent was performed for an aberrant left subclavian artery and left carotid artery. The patient was a 63-year-old man in whom left carotid artery stenosis and abnormal flow pattern of the left vertebral artery was accidently found during an ultrasound screening of his carotid artery. The right-sided aortic arch with the aberrant left subclavian artery was revealed by a cerebral angiogram via the right femoral artery. Despite difficulty in inserting a catheter at the origin of the aberrant left artery, the treatment was completed successfully. To our knowledge, endovascular treatment for an aberrant left subclavian artery has not been reported until date.

Carotid Artery Stenting for Near Occlusion with Full Collapse.

OBJECTIVE: Carotid near occlusions show a lower risk of stroke than other types of severe stenosis. However, emerging evidence suggests that near occlusion with full collapse differs from that without full collapse. The results of treatment with carotid artery stenting for near occlusion with full collapse are presented. METHODS: Between March 2007 and December 2020, 18 of 477 carotid artery stenting procedures were performed in patients with near occlusion with full collapse (3.8%). A total of 17 men and one woman with a mean age of 76.1 years were included. Eleven patients (61%) were symptomatic. The technical success rate, incidence of symptomatic stroke within 30 days, new ipsilateral ischemic lesions on diffusion tensor imaging within 48 hours after carotid artery stenting, and follow-up results (ipsilateral stroke rate and restenosis rate) were retrospectively assessed. RESULTS: The technical success rate was 100%. All carotid artery stenting procedures were performed using embolic protection devices. No symptomatic stroke occurred within 30 days. New ipsilateral ischemic lesions on magnetic resonance imaging were observed in 16.7% (3/18) of patients. Asymptomatic minor cerebral hemorrhage occurred in 2 patients (11.1%) with cerebral hyperperfusion syndrome. The median follow-up period was 77 months. Asymptomatic restenosis of 50% occurred in one patient (5.5%), and asymptomatic occlusion occurred in one patient (5.5%). During follow-up, no patients experienced ipsilateral stroke. Three patients (16.7%) died from nonneurological causes. CONCLUSIONS: Carotid artery stenting for near occlusion with full collapse seems to be a feasible and safe procedure that can be performed by an experienced neuro-interventional team.

Initial Experience of Coil Embolization for Unruptured Intracranial Aneurysm Combined with Neuroform Atlas and Undersized Flexible Coils.

Objective: Intraprocedural rupture (IPR) is a rare complication that can occur during endovascular treatment (EVT) of unruptured intracranial aneurysms (UIAs). However, it leads to high morbidity and mortality rates. Others have showed that coil flexibility is a risk factor for IPR. Neuroform Atlas (NA) stents can be deployed with 0.0165-inch microcatheters to enable stent assisted coiling (SAC) with a high likelihood. Undersized flexible coils can be inserted initially during SAC. This study aimed to determine whether SAC using NA and highly flexible coils for UIAs can be conducted without IPR. Methods: We retrospectively analyzed nine consecutive patients (mean age, 73.2 years; female, n = 6) who underwent SAC for UIAs combined with NA stents and undersized flexible coils between January 2017 and December 2019. Two aneurysms were located at the internal carotid artery (ICA), and one each was located at the ICA-posterior communicating, anterior communicating, middle cerebral, vertebral, vertebra-posterior inferior cerebral and basilar arteries. The mean size of the aneurysms was 4.6 (range, 3.1-8.6) mm. SAC proceeded using the jailing technique. All coils were selected from among the most flexible coils available. We retrospectively assessed technical success rates, aneurysm occlusion at final digital subtraction angiography (DSA), volume embolization ratios (VERs), rates of IPR and symptomatic stroke within 30 days, angiographic findings of aneurysm occlusion at 3 months post-procedure and late adverse events (frequency of aneurysmal rupture, ipsilateral ischemic stroke, and retreated targeted aneurysms). Results: The technical success rate was 100%. Complete occlusion (CO) was immediate in 8 (89%) patients and a neck remnant persisted in 1 (11%). No IPR or symptomatic stroke developed within 30 days. During a mean follow-up period of 11.8 months, CO persisted in 8 (89%) patients. No late adverse events occurred. Conclusion: The early clinical and angiographic findings of SAC for UIAs combined with an NA stent and undersized flexible coils were favorable for this series.

Computed tomography perfusion imaging after aneurysmal subarachnoid hemorrhage can detect cerebral vasospasm and predict delayed cerebral ischemia after endovascular treatment.

BACKGROUND: Endovascular treatment (ET) can improve angiographic cerebral vasospasm (CV) after aneurysmal subarachnoid hemorrhage, but was unrelated to clinical outcomes in previous analyses. Appropriate detection of CV and precise indications for ET are required. This study investigated whether changes in computed tomography perfusion (CTP) parameter can determine indications for ET in CV and predict its effectiveness. METHODS: Participants comprised 140 patients who underwent neck clipping or coil embolization. CTP was performed a week after aneurysmal treatment or when clinical deterioration had occurred. Patients were divided into ET and non-ET groups by propensity score matching. In addition, the ET group was divided into subgroups with and without new cerebral infarction (CI). All CTP images in the three groups were retrospectively investigated qualitatively and quantitatively. CI was diagnosed from CT at 3 months postoperatively. RESULTS: Of the 121 patients examined, 15 patients (11%) needed ET. In qualitative analysis, all ET group patients displayed extension of time-to-peak (TTP) at the region of vasospastic change, regardless of the presence of CI. Quantitative analysis showed significant decreases in cerebral blood volume (P < 0.01), cerebral blood flow (CBF) (P < 0.001), and extension in TTP (P < 0.01) in the ET group compared with the non-ET group. A significant decrease in CBF (P < 0.001) and extension in mean transit time (P < 0.001) was seen in the ET with CI subgroup compared with the ET without CI subgroup. CONCLUSION: CTP in the vasospastic period may be an indication for ET and predict the effectiveness of ET for CV to improve clinical outcomes.

Additional Assessment of Developed Occipital Sinus Using Intraoperative Indocyanine Green Videoangiography for a Safe Foramen Magnum Decompression-Technical Case Report.

BACKGROUND AND IMPORTANCE: Although foramen magnum decompression (FMD) with expansive duraplasty is a popular procedure for treating chiari malformation (CM), the common Y-shaped dural incision can lead to a life-threatening cerebral venous circulation disturbance in patients with a developed occipital sinus. Here, we describe the effectiveness of intraoperative indocyanine green video angiography (ICG-VA) for a CM type 1 (CM1) patient with a highly developed unilateral occipital sinus. CLINICAL PRESENTATION: A 40-yr-old woman presented with sensory disturbance on the left side of the body. Magnetic resonance imaging (MRI) revealed cerebellar tonsil herniation into the foramen magnum with cervical syringomyelia, and computed tomography additionally revealed skull anomalies: fontanel closure insufficiencies, cranial dysraphism, thin cranial bone, and dentition abnormalities. We diagnosed as symptomatic CM1 with syringomyelia associated with cleidocranial dysplasia, which is a dominantly inherited autosomal bone disease. Cerebral angiography revealed a developed right occipital sinus and hypoplasia of the bilateral transverse sinus. We performed FMD, paying special attention to the developed occipital sinus using ICG-VA to ensure a safe duraplasty. The angiography clearly highlighted a right-sided occipital sinus with a high contrast ratio, and no left-sided occipital sinus was visible. After a dural incision in a unilateral curvilinear fashion was safely completed, expansive duraplasty was performed. The sensory disorders experienced by the patient disappeared postoperatively. Postoperative MRI revealed elevation of the cerebellar tonsil and decreasing of the syringomyelia. CONCLUSION: Additional assessment using intraoperative ICG-VA provides useful information for a safe FMD, particularly in patients with complicated cerebral venous circulation anomalies.

Elective carotid stenting after urgent best medical treatment suppresses recurrent stroke in patients with symptomatic carotid artery severe stenosis.

OBJECTIVE: Urgent carotid endarterectomy and carotid artery stenting (CAS) for symptomatic advanced carotid artery stenosis is controversial because carry risks of hemorrhagic and thromboembolic complications. As treatments for preventing recurrent stroke have recently advanced, this study evaluated whether elective CAS with urgent best medical therapy reduces recurrent stroke for symptomatic severe carotid artery stenosis. PATIENTS AND METHODS: A total of 131 consecutive patients who underwent CAS for severe stenosis of the carotid artery between 2013-2017 were divided into acute ischemic minor stroke (AIMS) and Asymptomatic groups. The AIMS group comprised 59 patients presenting with minor stroke who underwent elective CAS with oral dual antiplatelet therapy, statin therapy, and add-on oral omega-3 fatty acid ethyl esters from 4 weeks before CAS. The Asymptomatic group comprised 72 patients treated with best medical therapy for 4 weeks before CAS. RESULTS: No recurrent ischemic stroke was observed under urgent best medical treatment before elective CAS in the AIMS group. Although the frequency of vulnerable plaque and degree of stenosis were much higher in the AIMS group, no significant differences were seen in perioperative complications. Baseline serum eicosapentaenoic acid (EPA) levels and EPA/ arachidonic acid (AA) were significantly lower in the AIMS group (p = 0.04, 0.04, respectively) and serum EPA/AA was significantly increased a day before CAS and 3 months after CAS compared with baseline. CONCLUSION: Urgent best medical treatment reduces recurrent stroke and facilitates safe elective CAS in patients with symptomatic and severe carotid artery stenosis.

Endovascular treatment of idiopathic intracranial hypertension caused by multiple venous sinus stenoses.

BACKGROUND: Idiopathic intracranial hypertension (IIH) shows symptoms by elevating intracranial pressure. Although sinus stenosis has been detected in many patients with IIH, the role of sinus stenosis in IIH remains obscure. Endovascular treatment for IIH due to transverse sinus stenosis has been frequently documented; however, IIH due to multiple sinus stenoses including the superior sagittal sinus (SSS) is rare. Here, we report a case of IIH due to multiple sinus stenoses treated by sinus stenting. CASE PRESENTATION: A 47-year-old woman suffered from intractable headache with IIH presented with stenosis of the right transverse and SSS. Stent placement was carried out since intracranial hypertension and trans-stenotic cerebral venous pressure gradient (CVPG) were presented, and her intractable headache disappeared. CONCLUSION: IIH can be caused by venous sinus stenoses and stent placement could be an appropriate treatment in patients who demonstrated a CVPG.

Stent-assisted coil embolization of unruptured vertebral artery dissecting aneurysms with the low-profile visualized intraluminal support stent, with five techniques: Technical note and case report.

BACKGROUND: Intracranial vertebral artery dissecting aneurysm (VADA) is rare and shows high morbidity and mortality rates when the aneurysm ruptures. Endovascular treatment for VADA is one of the optimal treatments, but the dominant side VA and its branches or perforators need to be preserved. We report a novel and successful stent-assisted coil embolization technique using the low-profile visualized intraluminal support (LVIS) stent, with five technical notes in three consecutive cases of unruptured vertebral artery dissecting aneurysm (VADA). CASE DESCRIPTION: We report three consecutive cases of unruptured VADA which involved a posterior inferior cerebellar artery (PICA), an anterior spinal artery, and perforators. Stent-assisted coil embolization with the LVIS stent was performed in all patients. The stent was carefully placed to obtain parent artery wall apposition at distal portion and with moderate pushing at aneurysm portion. The LVIS stent was placed with tailor-made wall apposition at perforating arterial side in the barrel view, and coil embolization was performed avoiding doughnut-like stent form to prevent perforator infarcts. All cases showed complete occlusion of the aneurysms with preservation of both parent artery and its branches and perforators patency. In three cases, clinical presentations were improved without ischemic complications. The median follow-up period was 1 year. At present, no recurrence and no complication have been observed. CONCLUSION: We demonstrate the coil embolization of VADA using LVIS stent with five techniques. Our techniques for the treatment of VADA using LVIS stent are safe and can minimize ischemic complications by creating suitable wall apposition to the orifices of branches or perforators.

Successful Emergent Endovascular Mechanical Thrombectomy for Pediatric and Young Adult Cerebral Venous Sinus Thrombosis in Coma.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a relatively uncommon cause of stroke in pediatric patients and young adults. The clinical course of CVST is also highly variable. In particular, coma has been noted as a predictor of poor outcome. The standard treatment for CVST in adults is systemic anticoagulation, which can lead to recanalization. Endovascular mechanical thrombectomy (EMT) is considered as possibly indicated in the event of failure to respond to anticoagulation or a comatose state. However, the role of endovascular therapy in the management of pediatric and young adult CVST is unclear. Here, we describe 3 cases of successful emergent EMT for pediatric and young adult CVST presenting in a comatose state. CASE DESCRIPTION: A 17-year-old boy presented with rapid deterioration and a comatose state despite anticoagulation using heparin. Emergent EMT was performed for CVST. Balloon percutaneous transmural angioplasty and catheter aspiration were repeatedly performed, and partial recanalization of the superior sagittal sinus was achieved by the end of the procedure. The child was discharged without neurologic deficits. Another 2 comatose cases with CVST underwent emergent EMT with balloon percutaneous transmural angioplasty and catheter aspiration, and partial recanalization was again achieved. These patients finally showed complete superior sagittal sinus recanalization and were discharged without neurologic deficits. CONCLUSION: Pediatric and young comatose CVST warrants endovascular mechanical thrombectomy as soon as possible.

Ex vivo-expanded highly purified natural killer cells in combination with temozolomide induce antitumor effects in human glioblastoma cells in vitro.

Glioblastoma is the leading malignant glioma with a poor prognosis. This study aimed to investigate the antitumor effects of natural killer cells in combination with temozolomide as the standard chemotherapeutic agent for glioblastoma. Using a simple, feeder-less, and chemically defined culture method, we expanded human peripheral blood mononuclear cells and assessed the receptor expression, natural killer cell activity, and regulatory T cell frequency in expanded cells. Next, using the standard human glioblastoma cell lines (temozolomide-sensitive U87MG, temozolomide-resistant T98G, and LN-18), we assessed the ligand expressions of receptors on natural killer cells. Furthermore, the antitumor effects of the combination of the expanded natural killer cells and temozolomide were assessed using growth inhibition assays, apoptosis detection assays, and senescence-associated ß-galactosidase activity assays in the glioblastoma cell lines. Novel culture systems were sufficient to attain highly purified (>98%), expanded (>440-fold) CD3-/CD56+ peripheral blood-derived natural killer cells. We designated the expanded population as genuine induced natural killer cells. Genuine induced natural killer cells exhibited a high natural killer activity and low regulatory T cell frequency compared with lymphokine-activated killer cells. Growth inhibition assays revealed that genuine induced natural killer cells inhibited the glioblastoma cell line growth but enhanced temozolomide-induced inhibition effects in U87MG. Apoptosis detection assays revealed that genuine induced natural killer cells induced apoptosis in the glioblastoma cell lines. Furthermore, senescence-associated ß-galactosidase activity assays revealed that temozolomide induced senescence in U87MG. Genuine induced natural killer cells induce apoptosis in temozolomide-sensitive and temozolomide-resistant glioblastoma cells and enhances temozolomide-induced antitumor effects in different mechanisms. Hence, the combination of genuine induced natural killer cells and temozolomide may prove to be a promising immunochemotherapeutic approach in patients with glioblastoma if the antitumor effects in vivo can be demonstrated.

Expression of peptide transporter 1 has a positive correlation in protoporphyrin IX accumulation induced by 5-aminolevulinic acid with photodynamic detection of non-small cell lung cancer and metastatic brain tumor specimens originating from non-small cell lung cancer.

BACKGROUND: Recently, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX fluorescence was reported to be a useful tool during total surgical resection of high-grade gliomas. However, the labeling efficacy of protoporphyrin IX fluorescence is lower in metastatic brain tumors compared to that in high-grade gliomas, and the mechanism underlying protoporphyrin IX fluorescence in metastatic brain tumors remains unclear. Lung cancer, particularly non-small cell lung cancer (NSCLC), is the most common origin for metastatic brain tumor. Therefore, we investigated the mechanism of protoporphyrin IX fluorescence in NSCLC and associated metastatic brain tumors. METHODS: Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) was employed to evaluate the protein and mRNA levels of five transporters and enzymes involved in the porphyrin biosynthesis pathway: peptide transporter 1 (PEPT1), hydroxymethylbilane synthase (HMBS), ferrochelatase (FECH), ATP-binding cassette 2 (ABCG2), and heme oxygenase 1 (HO-1). The correlation between protein, mRNA, and protoporphyrin IX levels in NSCLC cells were evaluated in vitro. Immunohistochemistry was used to determine proteins that played a key role in intraoperative protoporphyrin IX fluorescence in clinical samples from patients with NSCLC and pathologically confirmed metastatic brain tumors. RESULTS: A significant correlation between PEPT1 expression and protoporphyrin IX accumulation in vitro was identified by western blotting (P = 0.003) and qRT-PCR (P = 0.04). Immunohistochemistry results indicated that there was a significant difference in PEPT1 between the intraoperative protoporphyrin IX fluorescence-positive and protoporphyrin IX fluorescence-negative groups (P = 0.009). CONCLUSION: Expression of PEPT1 was found to be positively correlated with 5-ALA-induced protoporphyrin IX accumulation detected by photodynamic reaction in metastatic brain tumors originating from NSCLC.

False-positive inflammatory change mimicking glioblastoma multiforme under 5-aminolevulinic acid-guided surgery: A case report.

BACKGROUND: 5-aminolevulinic acid (5-ALA)-guided surgery is one of the gold standard perioperative modalities for maximum resection of malignant gliomas. However, it should be noted that 5-ALA fluorescence does not definitively indicate the presence of malignant tumor cells. CASE DESCRIPTION: We report a rare case of false-positive lesion mimicking glioblastoma multiforme (GBM) under 5-ALA-guided surgery. A 44-year-old woman presented with persistent headache and flickering in her eyes. Magnetic resonance imaging showed enhanced lesion with perifocal edema in the left occipital lobe. We performed 5-ALA-guided surgery for the lesion, during which strong fluorescence was observed, but evaluation of the intraoperative frozen section revealed only inflammatory cells. We concluded the tumor resection once adequate decompression had been achieved, and made the final pathological diagnosis of inflammatory change following an unknown infection. CONCLUSION: Neurosurgeons should be aware of false-positive lesions mimicking GBM under 5-ALA guided surgery.

Novel Human NK Cell Line Carrying CAR Targeting EGFRvIII Induces Antitumor Effects in Glioblastoma Cells.

BACKGROUND/AIM: Natural killer (NK) cells are considered potential antitumor effector cells. The aim of this study was to establish a novel type of a chimeric antigen receptor (CAR) NK cell line (CAR-KHYG-1) specific for epidermal growth factor receptor variant III (EGFRvIII)-expressing tumors and investigate the anti-tumor activity of EGFRvIII-specific-CAR-KHYG-1 (EvCAR-KHYG-1). MATERIALS AND METHODS: EvCAR-KHYG-1 was established by self-inactivated lentiviral-based transduction of the EvCAR gene and magnetic bead-based purification of EvCAR-expressing NK cells. The anti-tumor effects of EvCAR-KHYG-1 were evaluated using growth inhibition and apoptosis detection assays in glioblastoma (GBM) cell lines (EGFRvIII-expressing and non-expressing U87MG). RESULTS: The findings demonstrated that EvCAR-KHYG-1 inhibited GBM cell-growth via apoptosis in an EGFRvIII-expressing specific manner. CONCLUSION: This is the first study to establish a CAR NK cell line based on the human NK cell line KHYG-1. Therapy with EvCAR-KHYG-1 may be an effective treatment option for GBM patients.

ω-3 Fatty Acids Ethyl Esters Suppress Cerebral Vasospasm and Improve Clinical Outcome Following Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Occurrence of cerebral vasospasm after onset of aneurysmal subarachnoid hemorrhage (SAH) is a critical factor determining clinical prognosis. Eicosapentaenoic acid and docosahexaenoic acid, both ω-3 fatty acids (ω-3FA), can suppress cerebral vasospasm, and docosahexaenoic acid can relax vessel vasoconstriction and have neuroprotective effects. We investigated whether administration of ω-3FA prevented cerebral vasospasm occurrence and improved clinical outcomes after aneurysmal SAH. METHODS: From 2012 to 2015, 100 consecutive patients with aneurysmal SAH were divided into 2 periods. Between 2012 and 2013 (control period), 45 patients received standard management. Between 2014 and 2015 (ω-3FA period), 55 patients were prospectively treated with additional ω-3FA. Occurrence of cerebral vasospasm, occurrence of cerebral infarction caused by vasospasm, and modified Rankin Scale scores at 30 days and 90 days after onset of SAH for each period were evaluated and compared. RESULTS: The frequency of angiographic cerebral vasospasm in the ω-3FA period was significantly lower than in the control period (12 patients vs. 23 patients, P = 0.004). The frequency of new infarction caused by vasospasm in the ω-3FA period was also significantly lower than in the control period (5 patients vs. 14 patients, P = 0.011). There was a significant difference in modified Rankin Scale scores at 90 days after onset of SAH between the groups (P = 0.031). No adverse events were associated with ω-3FA administration. CONCLUSIONS: Administration of ω-3FA after aneurysmal SAH may reduce the frequency of cerebral vasospasm and may improve clinical outcomes.

Effectiveness of Intraoperative Indocyanine Green Videoangiography in Avoiding Failure in Proximal Clipping for Dissecting Vertebral Artery Aneurysm Associated with Double Origin of the Posterior Inferior Cerebellar Artery.

BACKGROUND: Double origin of the posterior inferior cerebellar artery (PICA) is rarely reported but is associated with cerebral aneurysm and dissection. Such aneurysms and dissections with unusual anatomic dispositions present the surgeon or physician with difficulties during treatment. CASE DESCRIPTION: A 65-year-old man presented with severe subarachnoid hemorrhage caused by a left dissecting VA, which was treated with proximal clipping. No aberrant origin of the PICA was recognized on initial imaging. Dissecting VA was confirmed from mural discoloration and obliterated by clip application proximal to the dissection. However, the dissecting VA that should have been eliminated from the circulation was still depicted on indocyanine green videoangiography. Meticulous inspection revealed an aberrant branch connecting the VA with the PICA. Termination of the dissecting VA was accomplished by division of the aberrant stem of the PICA and was confirmed by indocyanine green videoangiography. CONCLUSIONS: Despite its rarity, the possibility of a double origin of the PICA should be considered when treating a dissecting VA. Missing a small aberrant origin of the PICA would lead to treatment failure but can be detected by indocyanine green videoangiography during open direct surgery.