[Intraoperative Challenges in Endovascular Treatment for Ruptured Intracranial Aneurysms].

In aneurysmal subarachnoid hemorrhage, the highest therapeutic priority is to ensure immediate hemostasis without intraprocedural complications. This article outlines the possible intraoperative coil embolization complications for ruptured intracranial aneurysms and discuss strategies for their prevention and treatment.

Short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE): a multicenter, open-label, randomized clinical trial.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after stent-assisted coil embolization (SACE) for cerebral aneurysm remains uncertain. This randomized trial of short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE) aimed to clarify whether long-term DAPT can reduce the occurrence of ischemic stroke in patients with cerebral aneurysms treated by SACE compared with short-term DAPT. METHODS: Patients treated for cerebral aneurysm with SACE were enrolled from 17 hospitals in Japan. Patients were enrolled within 30 days after SACE and assigned in a 1:1 ratio to receive long-term (12 months) or short-term (3 months) DAPT with aspirin and clopidogrel. Randomization was performed centrally through a web-based system. The primary outcome was the time to ischemic stroke event during 3 to 12 months after SACE. This trial was registered with the Japan Registry of Clinical Trials (jRCTs051180141). RESULTS: A total of 142 patients were recruited from November 4, 2016 to January 7, 2019. Among them, 65 and 68 patients assigned to the long- and short-term DAPT groups, respectively, were included in the full analysis set. Ischemic stroke occurred in no patients in the long-term DAPT group and in one patient in the short-term DAPT group. The incidence rate did not differ between the groups (0.0 vs 2.1/100 person-years; log rank test, P=0.33). CONCLUSIONS: In this multicenter randomized controlled trial, there was not a statistically significant difference in the rate of ischemic strokes between long- and short-term DAPT.

[Current State of the Flow Diverter in Endovascular Treatment].

Since Pipeline Flex(Covidien/Medtronic)was approved in April 2015, flow diverter(FD)treatment has started in Japan. Three kinds of FDs(Pipeline, FRED and Surpass)are available now, and we have been able to treat a variety of aneurysms, including those that are giant-sized and located posterior circulation, which had been difficult to treat safely before the appearance of the FD. In addition, indications for FDs have been expanding with increasing evidence. However, there are some challenges that need to be overcome. First, thromboembolic complications due to high metallic amounts in FD must be considered. The long duration of antiplatelet therapy must be continued to reduce thromboembolic complications, but the precise required-duration of this therapy has not yet been determined. Second, FD treatment requires a few months before an aneurysmal cure is achieved. Therefore, there is a possibility of an aneurysmal rupture after FD deployment. In addition, there are some kinds of aneurysms for which FD treatment is less effective, such as aneurysms with a large branch vessel. In this review, I describe the details of each FD and the current state of FD, based on the evidence.

Relation between duration of dual antiplatelet therapy and risk of ischemic stroke after stent-assisted treatment of cerebral aneurysm (DAPTS ACE-registry).

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) in patients with cerebral aneurysm who undergo stent-assisted coil embolization (SACE) has not been established. We aimed to clarify the association between duration of DAPT and incidence of ischemic stroke in patients with cerebral aneurysm. METHODS: We registered patients with cerebral aneurysm who underwent SACE in 27 hospitals in Japan. Those treated with DAPT (aspirin and clopidogrel) were eligible for inclusion in a previously reported randomized control trial (RCT). Patients who were ineligible or refused to participate to the RCT were followed-up for 15 months after SACE as the non-RCT cohort. Our study examined both the RCT and non-RCT cohorts. The primary and secondary outcomes were ischemic stroke and hemorrhagic events. RESULTS: Among the 313 patients registered, 296 were included for analysis (of these, 136 were RCT patients and 160 were non-RCT patients). Patients who were treated with DAPT for more than 6 months (n=191) were classified as the long-term DAPT group. Those treated less than 6 months (n=105) were classified as the short-term group. The incidence of ischemic stroke did not significantly differ between the long-term group (2.5 per 100 person-years) and the short-term group (3.2 per 100 person-years); nor did incidence of hemorrhagic events (0.8 and 3.2 per 100 person-years, respectively). The period of DAPT was not significantly associated with incidence rates of ischemic stroke or hemorrhagic events. CONCLUSIONS: Duration of DAPT was not associated with the incidence of ischemic stroke in the first 15 months after SACE.

Coexisting filum terminale arteriovenous fistula and filum terminale lipoma treated with single-stage surgery: illustrative case.

BACKGROUND: Both filum terminale arteriovenous fistulas (FTAVFs) and filum terminale lipomas (FTLs) are rare. Because of this rarity, there is a paucity of data regarding concomitant FTAVF and FTL, and the optimal treatment remains to be defined. The authors describe a patient with coexisting FTAVF and FTL treated with single-stage surgery. OBSERVATIONS: A man in his 70s was referred to the authors' department because of a suspected spinal vascular malformation seen on magnetic resonance imaging that was performed to investigate lower limb weakness, intermittent claudication, and urinary incontinence. Previous imaging had shown a terminal lipoma with an internal flow void. Computed tomography angiography and digital subtraction angiography revealed an FTAVF, the feeder being a lateral sacral artery. The patient was treated surgically with curative intent. The FTL and tethered cord that had been identified by imaging were treated in the same procedure. Postoperative digital subtraction angiography showed absence of the abnormal vessels. The patient was discharged home on the 19th postoperative day. LESSONS: When considering treatment, it is important to determine whether symptoms are attributable mainly to FTL, tethered cord, or FTAVF. One-stage treatment is useful because it eliminates both the FTAVF and the factors that led to its development.

Stent infection and pseudoaneurysm formation after carotid artery stent treated by excision and in situ reconstruction with polytetrafluoroethylene graft: A case report.

BACKGROUND: Stent infection after carotid artery stenting (CAS) can be a life-threatening postoperative complication, but there is a paucity of data due to its exceedingly low frequency. We report a case of stent infection with pseudoaneurysm formation after CAS that was treated through replacing the infected stent and pseudoaneurysm with a polytetrafluoroethylene (PTFE) synthetic vessel graft. CASE DESCRIPTION: An 86-year-old man was treated for the right internal carotid artery with CAS in local hospital. One month after stenting, he suffered aspiration pneumonia and septicemia. Three months after stenting, swelling and tenderness of the right side of his neck appeared. His general condition deteriorated due to septicemia and he was unable to ingest anything by mouth as a result of decreasing levels of consciousness. He was transferred to our hospital. Computed tomography and digital subtraction angiography showed the presence of a pseudoaneurysm around the stent. The neck mass enlarged daily and surgical intervention was required to prevent closure of the airway. Stent and pseudoaneurysm resection and in situ reconstruction with a PTFE synthetic vessel graft were performed. The patient returned to his local hospital 36 days after surgery and had a modified Rankin Score of 5. CONCLUSION: Although the risk of reinfection is high due to the nature of artificial material, stent/pseudoaneurysm resection and in situ reconstruction with a PTFE synthetic vessel graft might be one of the best options for patients suffering stent infection after CAS. To the best of our knowledge, this is the first report of treatment using this material.

Magnetic Resonance Relaxometry for Tumor Cell Density Imaging for Glioma: An Exploratory Study via 11C-Methionine PET and Its Validation via Stereotactic Tissue Sampling.

One of the most crucial yet challenging issues for glioma patient care is visualizing non-contrast-enhancing tumor regions. In this study, to test the hypothesis that quantitative magnetic resonance relaxometry reflects glioma tumor load within tissue and that it can be an imaging surrogate for visualizing non-contrast-enhancing tumors, we investigated the correlation between T1- and T2-weighted relaxation times, apparent diffusion coefficient (ADC) on magnetic resonance imaging, and 11C-methionine (MET) on positron emission tomography (PET). Moreover, we compared the T1- and T2-relaxation times and ADC with tumor cell density (TCD) findings obtained via stereotactic image-guided tissue sampling. Regions that presented a T1-relaxation time of >1850 ms but <3200 ms or a T2-relaxation time of >115 ms but <225 ms under 3 T indicated a high MET uptake. In addition, the stereotactic tissue sampling findings confirmed that the T1-relaxation time of 1850-3200 ms significantly indicated a higher TCD (p = 0.04). However, ADC was unable to show a significant correlation with MET uptake or with TCD. Finally, synthetically synthesized tumor load images from the T1- and T2-relaxation maps were able to visualize MET uptake presented on PET.

Cerebellar preference of luminal A and B type and basal ganglial preference of HER2-positive type breast cancer-derived brain metastases.

The purpose of the current study was to investigate the hypothesis that the spatial distribution of brain metastases could be affected by the biological subtypes of breast cancer. CT (n=1) or MRI (n=66) images of 67 patients with a total of 437 treatment-naive brain metastases from breast cancer were retrospectively reviewed. Patients were grouped according to the biological subtype of the tumor [luminal A, 28; luminal B, 9; human epidermal growth factor receptor 2 (HER2) positive, 14; triple-negative breast cancer (TNBC), 16]. All images were standardized to the human brain MRI atlas provided by the Montreal Neurological Institute 152 database. The distribution pattern of brain metastases after image standardization was analyzed. The cerebellum and the frontal lobe were more commonly affected by breast cancer brain metastases. Brain metastases from luminal A and B types of breast cancer arose more often in the cerebellum. Brain metastases from HER2-positive type breast cancer occurred more often in the putamen and the thalamus and less frequently in the cerebellum than other types (P=0.0057). The subtypes of breast cancer are related to differences in the spatial distributions of their brain metastases. These differences may be utilized to plan different cranial irradiation strategies according to the breast cancer subtypes.

Characteristics of pial brain arteriovenous malformations with transdural arterial supply.

PURPOSE: Transdural blood supply (TDBS) to pial brain arteriovenous malformations (BAVM) is uncommon and believed to be related to vascular endothelial growth factor - induced angiogenesis. The aim of this study was to define the BAVM characteristics in relation to presence and volume of TDBS. METHODS: BAVMs managed at our institution between January 2006 and December 2016 who subsequently underwent complete digital subtraction angiography (DSA) were included. They were classified based on presence of TDBS as well as volume of TDBS. RESULTS: Of the 641 BAVM patients managed during the recruitment period, 387 (391 BAVMs) had complete pretreatment DSAs. Forty-three (11.0 %, 10 ruptured) BAVMs exhibited TDBS. With TDBS group had a significantly greater proportion of large nidus (> 3.1 cm) than the Without TDBS group (85.1 % vs 19.5 %, p < 0.01) and were more frequently temporal (32.6 % vs 14.7 %, p < 0.01) and occipital (25.6 % vs 13.5 %, p < 0.05) in location. In unruptured BAVMs, the presence of headaches was significantly more prevalent when the malformation harboured TDBS compared to not (57.6 vs 34.8 %, p < 0.05). The annual rupture rate among unruptured BAVMs treated by conservative management was 4.7 % in the With TDBS (n = 12) group and 0% (n = 21) in BAVMs with TDBS that underwent treatment including surgery, endovascular therapy, or radiosurgery. CONCLUSION: BAVMs with TDBS are more likely to be associated with a large nidus and located in the temporal and occipital lobes. Headache is more frequently associated with the presence of TDBS. Rupture rate of unruptured BAVMS with TDBS can be effectively reduced following treatment.

Efficacy of endovascular intratumoral embolization for meningioma: assessment using dynamic susceptibility contrast-enhanced perfusion-weighted imaging.

BACKGROUND: In preoperative embolization for intracranial meningioma, endovascular intratumoral embolization is considered to be more effective for the reduction of tumorous vascularity than proximal feeder occlusion. In this study, we aimed to reveal different efficacies for reducing tumor blood flow in meningiomas by comparing endovascular intratumoral embolization and proximal feeder occlusion using dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI). METHODS: 28 consecutive patients were included. DSC-PWI was performed before and after embolization for intracranial meningiomas. Normalized tumor blood volume (nTBV) of voxels of interest of whole tumors were measured from the DSC-PWI data before and after embolization. ΔnTBV% was compared between the cases that received intratumoral embolization and proximal feeder occlusion. RESULTS: ΔnTBV% in the intratumoral embolization group (42.4±29.8%) was higher than that of the proximal feeder occlusion group (15.3±14.3%, p=0.0039). We used three types of embolic materials and ΔnTBV% did not differ between treatments with or without the use of each material: 42.8±42.4% vs 28.7±20.1% for microspheres (p=0.12), 36.1±20.6% vs 28.1±41.1% for n-butyl cyanoacrylate (p=0.33), and 32.3±37.3% vs 34.1±19.0% for bare platinum coils (p=0.77). CONCLUSIONS: The flow reduction effect of intratumoral embolization was superior to that of proximal feeder occlusion in preoperative embolization for intracranial meningioma in an assessment using DSC-PWI.

Endovascular Therapy of Acute Ischemic Stroke in Patients with Large-Vessel Occlusion Associated with Active Malignancy.

PURPOSE: There is limited data on the effectiveness of endovascular therapy (EVT) in stroke patients with active malignancy. In this study, we investigated the outcome of EVT for acute ischemic stroke for patients with active malignancy compared to those without malignancy. METHODS: We selected patients who underwent EVT for acute ischemic stroke between January 2015 and July 2019. Patients were divided into two groups, those with active malignancy (oncology group - OG) and those without (non-oncology group, NOG). RESULTS: 300 patients were included in this study. There were 19 EVT procedures (18 patients) in the OG and 285 procedures (282 patients) in the NOG. There was no difference in recanalization success rate (mTICI 2b & 3) between the groups: 94.7% versus 80.9% in OG and NOG respectively (p = 0.13). Success rate using the direct aspiration (ADAPT) technique of EVT was not different between compared groups (42.9% versus 67.7%; p = 0.18). However, when using smaller-caliber aspiration devices, ADAPT was less successful in OG (0.0% versus 64.7%, p < 0.05). There was no difference in recanalization success rate of EVT when using a stent-retriever or combined technique. Patients in the OG had a less favorable functional outcome than in the NOG group (mRS 0-2 at 90-days post event: 22.2% versus 48.2%, p < 0.05) CONCLUSION: The technical success rate of EVT in patients with active malignancy is similar to the general population of stroke patients. Interestingly, the success rate of EVT using the ADAPT technique was lower in the OG when using smaller caliber aspiration devices.

The impact of EGFR mutation status and single brain metastasis on the survival of non-small-cell lung cancer patients with brain metastases.

BACKGROUND: Molecular and genetic alterations of non-small-cell lung cancer (NSCLC) now play a vital role in patient care of this neoplasm. The authors focused on the impact of epidermal growth factor receptor mutation (EGFR-mt) status on the survival of patients after brain metastases (BMs) from NSCLC. The purpose of the study was to understand the most desirable management of BMs from NSCLC. METHODS: This was a retrospective observational study analyzing 647 patients with NSCLC, including 266 patients with BMs, diagnosed at our institute between January 2008 and December 2015. EGFR mutation status, overall survival (OS) following diagnosis, OS following BMs, duration from diagnosis to BMs, and other factors related to OS and survival after BMs were measured. RESULTS: Among 647 patients, 252 (38.8%) had EGFR mutations. The rate and frequency of developing BMs were higher in EGFR-mt patients compared with EGFR wildtype (EGFR-wt) patients. EGFR-mt patients showed longer median OS (22 vs 11 months, P < .001) and a higher frequency of BMs. Univariate and multivariate analyses revealed that good performance status, presence of EGFR-mt, single BM, and receiving local therapies were significantly associated with favorable prognosis following BM diagnosis. Single metastasis, compared with multiple metastases, exhibited a positive impact on patient survival after BMs in EGFR-mt patients, but not in EGFR-wt NSCLC patients. CONCLUSIONS: Single BM with EGFR-mt performed better than other groups. Furthermore, effective local therapies were recommended to achieve better outcomes.

Validation of magnetic resonance imaging-based automatic high-grade glioma segmentation accuracy via 11C-methionine positron emission tomography.

Brain Tumor Image Analysis (BraTumIA) is a fully automated segmentation tool dedicated to detecting brain tumors imaged by magnetic resonance imaging (MRI). BraTumIA has recently been applied to several clinical investigations; however, the validity of this novel method has not yet been fully examined. The present study was conducted to validate the quality of tumor segmentation with BraTumIA in comparison with results from 11C-methionine positron emission tomography (MET-PET). A total of 45 consecutive newly diagnosed high-grade gliomas imaged by MRI and MET-PET were analyzed. Automatic tumor segmentation was conducted by BraTumIA and the resulting segmentation images were registered to MET-PET. Three-dimensional conformal association between these two modalities was calculated, considering MET-PET as the gold standard. High underestimation and overestimation errors were observed in tumor segmentation calculated by BraTumIA compared with MET-PET. Furthermore, when the tumor/normal ratio threshold was set at 1.3 from MET-PET, the BraTumIA false-positive fraction was ~0.4 and the false-negative fraction was 0.9. By tightening this threshold to 2.0, the BraTumIA false-positive fraction was 0.6 and the false-negative fraction was 0.6. Following comparison of segmentation performance with BraTumIA with regard to glioblastoma (GBM) and World Health Organization (WHO) grade III glioma, GBM exhibited better segmentation compared with WHO grade III glioma. Although BraTumIA may be able to detect enhanced tumors, non-enhancing tumors and necrosis, the spatial concordance rate with MET-PET was relatively low. Careful interpretation is therefore required when using this technique.

Therapeutic strategy against ischemic stroke with the concept of neurovascular unit.

Stroke is one of the leading causes of death and disability globally. Although thrombolytic therapy by t-PA and mechanical thrombectomy have improved outcomes of ischemic stroke patients, both of these approaches are applicable to limited numbers of patients owing to their time constraints. Therefore, development of other treatment approaches such as developing neuroprotective drugs and nerve regeneration therapy is required to overcome ischemic stroke. The concept of the neurovascular unit (NVU) was formalized by the Stroke Progress Review Group of the National Institute of Neurological Disorders and Stroke in 2001. This concept emphasizes the importance not just of neurons but of the interactions between neurons, endothelial cells, astroglia, microglia and associated tissue matrix proteins to investigate the pathological condition of ischemic stroke. Many reports have been published about these interactions. This review focuses on the roles of cells that surround cerebral vasculature, especially endothelial cells, and reports therapeutic strategies against ischemic stroke from four points of view including angiogenesis, neurotrophic effects, protection of NVU components and regenerative therapy.

Enlargement of papillary glioneuronal tumor in an adult after a follow-up period of 10 years: a case report.

Papillary glioneuronal tumor (PGNT) is a rare brain tumor grouped under mixed glioneuronal tumors according to the World Health Organization Classification of the Central Nervous System. The natural history of this pathology is not yet well documented. We report a case of PGNT that increased in size after a follow-up period of 10 years. An enlarged cyst wall and nodule showed a low intensity signal on T2*-weighted, suggesting hemorrhage during the clinical course. Characteristic pathological findings along with absence of BRAFV600E mutation identified the tumor as PGNT. The tumor characteristics of PGNT are discussed based on the presented case, with reference to the existing literature.

Intracranial stenting for nilotinib treatment-associated cerebrovascular stenosis in chronic myeloid leukemia.

One of the second-generation tyrosine kinase inhibitors (TKIs), nilotinib, is increasingly used for imatinib-resistant or intolerant chronic myeloid leukemia (CML). Nilotinib is considered well tolerated with few side effects including hyperglycemia, hyperbilirubinemia and elevated levels of pancreatic enzymes. However, there is growing evidence that nilotinib accelerates atherosclerosis and causes peripheral arterial occlusive disease such as stroke, transient ischemic attack (TIA) and cardiovascular diseases. Herein, we report a case of a 74-year-old male CML patient with intracranial stenosis of the internal carotid artery developed during treatment with nilotinib successfully cured by the intracranial stent, Wingspan.

Voxel-Based Lesion Mapping of Cryptogenic Stroke in Patients with Advanced Cancer: A Detailed Magnetic Resonance Imaging Analysis of Distribution Pattern.

BACKGROUND: Ischemic stroke is one form of cancer-associated thrombosis that can greatly worsen a patient's performance status. The present investigation aimed to elucidate the characteristic distribution pattern(s) of cryptogenic stroke lesions using a voxel-based lesion-mapping technique and examine the differences in clinical manifestations between cryptogenic and conventional strokes in patients with advanced cancer. METHODS: Data from 43 patients with advanced cancer who developed acute ischemic stroke were retrospectively collected. Stroke etiology was grouped into either cryptogenic or conventional stroke etiology according to the ASCO stroke score. Clinical data were reviewed, and voxel-based lesion mapping using diffusion-weighted imaging (DWI) was performed to visualize the cross-patient spatial distribution of the lesions. RESULTS: Of the 43 patients, 25 were classified as having cryptogenic stroke etiology and 18 were classified as having conventional stroke etiology. Median survival time of patients from stroke onset was 96 days for cryptogenic stroke etiology and 570 days for conventional stroke etiology (P = .01). D-dimer of patients was significantly higher in cryptogenic stoke etiology than in conventional stroke etiology (P = .006). Voxel-based lesion mapping showed that DWI hyperintense lesions accumulated at cortical and internal watershed areas of the cerebrum and at the vascular border zone of the superior cerebellar and posterior inferior cerebellar arteries at the cerebellum. CONCLUSIONS: Voxel-based lesion mapping for cryptogenic stroke in patients with advanced cancer showed that lesions accumulated at vascular border zones within the brain both at the cerebrum and at the cerebellum, but not at perforating arterial territories.