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DS-1040 is a novel inhibitor of the activated form of thrombin-activatable fibrinolysis inhibitor that may have therapeutic potential in thromboembolic diseases, such as acute ischemic stroke (AIS) or pulmonary embolism. We undertook a Phase I clinical trial to investigate the safety, pharmacokinetics, and pharmacodynamics of DS-1040 in Japanese patients who were eligible for thrombectomy following AIS.The trial enrolled patients with AIS due to large vessel occlusion, who were planned for thrombectomy within 8 h of symptom onset. Subjects were randomized to receive a single intravenous infusion of placebo or DS-1040 (0.6, 1.2, 2.4 or 4.8 mg) in a sequential-cohort design. The primary endpoints were the incidence of intracranial hemorrhage (ICH) and major extracranial bleeding within 36 and 96 h, respectively, of treatment initiation. Treatment-emergent adverse events (TEAEs) and pharmacokinetic/pharmacodynamic parameters were also assessed.Nine patients received placebo and 32 patients received DS-1040. There were no cases of symptomatic ICH or major extracranial bleeding with either placebo or DS-1040 after 36 and 96 h. One patient, who received DS-1040 0.6 mg, experienced a subarachnoid hemorrhage that was considered to be drug-related. Three patients died (2 placebo, 1 DS-1040), but no deaths were adjudicated as study drug-related. In vivo exposure to DS-1040 increased in proportion to dosage, but no clear dose-response relationship was seen for D-dimer levels and thrombin-activatable fibrinolysis inhibitor activity.Single doses of DS-1040 0.6-4.8 mg were well tolerated in Japanese patients with AIS undergoing thrombectomy.NCT03198715; JapicCTI-163164.

Surgical treatment should be considered for patients with severe vertebrobasilar artery (VBA) stenosis or progressive symptoms, but there is currently no clear treatment algorithm. We report a case of symptomatic intracranial vertebral artery stenosis with repeated cerebral infarction treated by percutaneous transluminal angioplasty (PTA) and stenting and monitoring of oxygen saturation by a brain oximeter. The patient was a 76-year-old man referred to our hospital due to infarction in the right cerebellum. Angiography showed 60% stenosis in the right vertebral artery and 90% stenosis in the left vertebral artery with progressive stenosis in the left. The patient was treated with intravenous and oral triple antiplatelet therapy but had dizziness again with new cerebral infarctions in the left cerebellum and right pontine. We shaved the patient's hair up to the superior nuchal line and placed left and right oximeter probes on each cerebellar hemisphere (2 cm lateral and 2 cm caudal from the external occipital protuberance). Under evaluation of blood flow in the posterior circulation with INVOS Cerebral/Somatic Oximeter, PTA and stent placement were performed for left vertebral artery stenosis. Postoperatively, the dizziness disappeared, and the patient was discharged on his own with good outcome. He has not had a recurrent stroke in over 6 years. Although medical treatment is generally considered the first choice for VBA stenosis, recurrent cerebral infarction occurs at a high rate in symptomatic lesions, and the prognosis is poor. In addition, the perioperative complication rate is not low, and there is no established method for evaluating perfusion of posterior circulation. The brain oximeter is already known to be useful in carotid artery (CA) revascularisation. In this report, we were able to perform a minimally invasive evaluation of blood flow in the posterior circulation using the brain oximeter which might be useful for surgical revascularisation not only in CA but also in VBA.

Background Pilocytic astrocytomas (PAs) are central nervous system tumors with variable prognosis and poorly understood risk factors. Little evidence exists regarding the effect of age on mortality in PA. Therefore, we conducted a thorough characterization of PA in the US. Methods We queried the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018 to extract age-adjusted incidence rate (AAIR), age-adjusted mortality rate (AAMR), and survival data on PA. The age group comparisons for each measure varied depending on available SEER data. We compared trends in AAIR and AAMR by two age groups (children, 0-19 years; adults, 20 + years) and by sex. The cumulative incidence function and the Fine-Gray competing risk model were applied by 0-19, 20-39, 40-59, and 60 + years of age groups. Results This study included 5211 incident PA and 462 PA-specific deaths between 2000 and 2018. Trends in AAIRs and AAMRs were almost constant between 2000 and 2018. Average AAIRs had a sharp peak in 1-4 years of age groups, whereas AAMRs had a gradual peak in 80-84 years of age groups. Age groups, tumor location, and race/ethnicity were significantly associated with PA-specific death, whereas only age was associated with other cause of deaths. Conclusions Trends in AAIRs and AAMRs were constant regardless of age. PAs in older populations, especially over 60 years old, have higher incidence of death than those in younger populations.

Development of extracranial carotid artery aneurysm (ECCA) after carotid endarterectomy (CEA) is a rare complication, occurring in connection with

Cerebral hyperperfusion syndrome (CHS) is a rare but fatal perioperative complication after surgical correction of carotid stenosis. Despite numerous treatment options for preventing CHS, it does occur in some patients. We developed the outlet gate technique (OGT), in which the embolic balloon was deflated gradually in accordance with the ratio of oxygen saturation measured by a brain oximeter of the ipsilateral brain region to that in the contralateral region. Between June 2017 and May 2018, 39 patients with carotid stenosis underwent endovascular carotid revascularization procedures; of these, 20 underwent the procedure with the OGT. CBO was measured five times in those 20 patients: before the procedure, with the embolic protection device (EPD) on, with the EPD off, during the procedure, and after the procedure. Preventive treatment options were used more frequently in these patients, and although their surgical status seemed more complicated, perioperative complications were not increased. There were almost significant differences between CBO values except between those during and after the procedure with the OGT. This showed that the OGT allowed for stabilization of the CBO and thus has the potential to prevent CHS.

Cerebral hyperperfusion syndrome (CHS) is a rare but fatal perioperative complication after surgical correction of carotid stenosis. Despite numerous treatment options for preventing CHS, it does occur in some patients. We developed the outlet gate technique (OGT), in which the embolic balloon was deflated gradually in accordance with the ratio of oxygen saturation measured by a brain oximeter of the ipsilateral brain region to that in the contralateral region. Between June 2017 and May 2018, 39 patients with carotid stenosis underwent endovascular carotid revascularization procedures; of these, 20 underwent the procedure with the OGT. CBO was measured five times in those 20 patients: before the procedure, with the embolic protection device (EPD) on, with the EPD off, during the procedure, and after the procedure. Preventive treatment options were used more frequently in these patients, and although their surgical status seemed more complicated, perioperative complications were not increased. There were almost significant differences between CBO values except between those during and after the procedure with the OGT. This showed that the OGT allowed for stabilization of the CBO and thus has the potential to prevent CHS.

When it is difficult to approach the brachial or femoral artery during endovascular surgery, an alternative approach is the direct puncture of the carotid artery. In this case of a giant cerebral aneurysm, we punctured the carotid artery directly and performed flow diverter stent placement and endosaccular coil embolization. Although the procedure required two thick access routes, it was performed after administering two antiplatelet drugs and an anticoagulant in order to achieve reliable hemostasis of the puncture sites after the operation. Direct common carotid artery puncture through a cervical skin incision is useful, because it ensures multiple access routes safely and provides secure hemostasis of the puncture sites.

Background Chronic subdural hematoma (CSDH) with cerebrospinal fluid hypovolemia syndrome (CHS) remains refractory to standard treatment with hematoma drainage by burr hole and irrigation and/or epidural blood patch. Previously, we reported the utility of middle meningeal artery (MMA) embolization for intractable CSDH. In this study, we present the usefulness of MMA embolization as a treatment for CSDHs with CHSs. Cases We present two cases of CSDHs with CHSs occurring in patients, 1 treated with burr hole craniotomy and irrigation, and the other treated with the epidural blood patch. Both patients exhibited similar-appearing bilateral relatively-thin hematomas, hyperplasia, and enhanced contrast effects in the dura mater, and extradural hygroma in the cervical portion on enhanced magnetic resonance imaging scans. Also, to reviewing prior literature and imaging findings, they had already undergone conventional treatment. We added MMA embolization treatment and they followed a good course. Results Despite the known intractable outcomes of patients with CSDHs with CHSs, MMA embolization worked well in the current case series. Conclusion MMA embolization might be considered as a preferred therapeutic option for CSDHs with CHSs in order to buy time before the epidural blood patch starts working.

Objective A subset of patients with chronic subdural hematoma (CSDH) remains refractory to standard treatment with hematoma drainage by burr-hole craniotomy and irrigation. We recently reported the usefulness of middle meningeal artery (MMA) embolization for intractable CSDH in patients with multiple intractable risk factors. We present the midterm outcomes of MMA embolization in patients with intractable CSDHs. Methods and Results Seventeen consecutive patients (average age, 76.4 years; 12 men [71%]) underwent MMA embolization of CSDH from January 2014 to July 2017. Earlier interventions included embolization using N-butyl-2-cyanoacrylate (although trisacryl gelatin microspheres were used in recent cases), followed by burr-hole craniotomy and irrigation in all cases. None of the patients experienced perioperative complications or postoperative recurrence. The modified Rankin Scale scores, which were unfavorable at admission, improved significantly at discharge but were comparable to those at the time of hospitalization when measured during the follow-up period. Although the patients required rehospitalization at other departments for unrelated causes, none required rehospitalization in our department. Conclusions Despite the known unfavorable outcomes of patients with intractable CSDHs, MMA embolization was not associated with recurrent CSDH or rehospitalization in our department in the current case series. MMA embolization should be considered a preferred therapeutic option for intractable CSDHs.

Objective Low-profile visualized intraluminal support (LVIS®) is a braided stent utilized for stent-assisted coil embolization of intracranial aneurysms. In this report, we review the technical notes of coil embolization for unruptured intracranial aneurysm using LVIS® stents. Case description We reported six consecutive cases of unruptured saccular aneurysm of the internal carotid artery all of whom underwent stent-assisted coil embolization with the LVIS® stent. After the first three cases, dry lab training using a complicated parent artery model allowed us to determine how to effectively place an LVIS® stent and to shorten operative time significantly. All patients were followed up for at least 1 year after the procedure. Thus far, none of the patients have experienced recurrence or complications. Conclusions Our experience with patients undergoing stent-assisted coil embolization using LVIS® stents before and after dry lab training reveal that several simple technical tips, including careful measurement of the parent artery diameter, choice of an appropriate stent size, and evasion of pushing or pulling the stent beyond what is necessary, are important for easy and stable deployment of LVIS® stents.

A 67-year-old patient presented with a headache, vertigo and nausea, followed by a disturbance of consciousness. CT and MRI showed venous ectasia at the left cerebellopontine angle and extensive oedema in the left cerebellum. Angiography demonstrated a dural arteriovenous fistula that appeared at the left superior petrosal sinus–cavernous sinus) junction. After the evaluation of the shunt point, occluded areas were recanalised via the femoral vein with a quadriaxial catheter system using a 6-Fr guiding sheath, 6-Fr guiding catheter, 4.2-Fr catheter and microcatheter. Selective coil embolisation was performed, resulting in shunt removal.

During endovascular neurosurgery, various devices, such as catheters, are passed through the intracranial arteries to access target vessels; the arteries can thereby be perforated. Even though such incidents are serious and should be dealt with appropriately, few case reports or standard procedures have been published. Herein, we report two cases of arterial perforation that occurred recently in our hospital. In the first case, the patient had been treated preoperatively using feeder occlusion of an arteriovenous malformation; the microcatheter perforated the feeder, which branched from the middle cerebral artery. The feeder and perforation site were occluded by injection of n-butyl 2-cyanoacrylate (NBCA) through the same microcatheter, and complete hemostasis was thereby achieved. The second case occurred during an embolization of the middle meningeal artery (MMA) to treat a refractory chronic subdural hematoma;the microcatheter perforated a branch of the MMA. Both the perforation and the artery were embolized using platinum coils and by injecting NBCA, and hemostasis was achieved. Considering the anatomical and pathological properties of the injured vessels, favorable results were achieved with appropriate intervention.

Aim Severe neurogenic pulmonary edema (NPE) can occur in a variety of brain insults, including subarachnoid hemorrhage (SAH), and severe case of NPE can cause devastating consequences. But the literature on the treatment strategy about aneurysmal SAH with NPE is very scant. We present that SAH patients with severe NPE, who were treated first by embolization of aneurysm followed by insertion of lumbar spinal drainage, had comparatively good outcome. Material and methods We present 12 consecutive cases of aneurysmal SAH with NPE in the acute stage, which were treated by endovascular treatment between April 2002 and December 2012. We classified the patients according to the Hunt and Hess grading system as follows: grade-3 (1 patient), grade-4 (4 patients), and grade-5 (7 patients). All patients needed respiratory management, with the assistance of a ventilator, and underwent endovascular treatment for the ruptured aneurysms within 72 hours from onset. For all the patients, immediately after the endovascular treatment, we performed lumbar spinal drainage. Results The pulmonary edema disappeared rapidly after respiratory management and endovascular treatment. The outcomes were as follows: good recovery (GR; 3 patients), moderate disability (MD; 4 patients), severe disability (SD; 3 patients), and death (D; 2 patients). Five patients (42%) developed pneumonia, and we postponed extubation until recovery from pneumonia. The cause for severe disability and death was symptomatic vasospasm and primary brain damage. No patients had rebleeding from ruptured aneurysms. Conclusion Endovascular treatment for ruptured aneurysm and placement of lumbar spinal drainage is an excellent treatment option for severe SAH with NPE.