Trends in prior antithrombotic medication and risk of in-hospital mortality after spontaneous intracerebral hemorrhage: the J-ICH registry.

Spontaneous intracerebral hemorrhage (SICH) remains a devastating form of stroke. Prior use of antiplatelets or warfarin before SICH is associated with poor outcomes, but the effects of direct oral anticoagulants (DOACs) remain unclear. This study aimed to clarify trends in prior antithrombotic use and to assess the associations between prior use of antithrombotics and in-hospital mortality using a multicenter prospective registry in Japan. In total, 1085 patients were analyzed. Prior antithrombotic medication included antiplatelets in 14.2%, oral anticoagulants in 8.1%, and both in 1.8%. Prior warfarin use was significantly associated with in-hospital mortality (odds ratio [OR] 5.50, 95% confidence interval [CI] 1.30-23.26, P < 0.05) compared to no prior antithrombotic use. No such association was evident between prior DOAC use and no prior antithrombotic use (OR 1.34, 95% CI 0.44-4.05, P = 0.606). Concomitant use of antiplatelets and warfarin further increased the in-hospital mortality rate (37.5%) compared to warfarin alone (17.2%), but no such association was found for antiplatelets plus DOACs (8.3%) compared to DOACs alone (11.9%). Prior use of warfarin remains an independent risk factor for in-hospital mortality after SICH in the era of DOACs. Further strategies are warranted to reduce SICH among patients receiving oral anticoagulants and to prevent serious outcomes.

Efficacy of Monitoring for Multiple Antiplatelet Therapy during Intracranial Stent Placement: A Preliminary Study.

Objective: During cerebral aneurysm embolization using intracranial stents, platelet aggregation increases owing to increased wall shear stress and a loss of vascular endothelial function at the stent implantation site. Preoperative multiple antiplatelet therapy was introduced to prevent severe thromboembolic complications due to increased platelet aggregation. However, specific guidelines for the administration and pharmacological evaluation of this therapy do not exist currently. We examined the benefits of perioperative platelet aggregation monitoring in a cohort of patients. Methods: We had 377 patients with unruptured intracranial aneurysms who underwent stent-assisted embolization at our hospital between December 2012 and November 2019. We ultimately included 181 patients in our final analysis. These patients were continuously administered aspirin (100 mg/day) and clopidogrel (75 mg/day) for more than 5 days before the procedure to the post-procedural period. Of these patients, 30 patients who underwent light transmission aggregometry (LTA) before procedure, post-procedure (3 days after procedure), and at first post-discharge clinic visit were included as the subjects. The following characteristics were studied: age; sex; presence/absence of hypertension, dyslipidemia, and/or diabetes mellitus; location of aneurysm; type/number of stent; technique for stent placement; duration of preoperative multiple antiplatelet therapy; perioperative platelet aggregation test results; and postoperative ischemic or hemorrhagic complications. Results: Among these 30 patients, the median duration of antiplatelet therapy prior to the preoperative platelet aggregation measurements was 7 (interquartile range [IQR]: 6-8) days, and post-discharge measurement of LTA was performed at a median period of 27 (IQR: 22-35.5) days after procedure. The preoperative, postoperative, and first post-discharge clinic visit LTA values for adenosine diphosphate (ADP)-induced platelet aggregation were 50% (IQR: 44-54%), 42.5% (IQR: 36-48%), and 36% (IQR: 32-40%), respectively. These results represented gradual decrease in LTA values and a significant difference between the preoperative and post-discharge values. The LTA values for collagen aggregation showed a significant difference evident between the preoperative and post-discharge values; preoperative 38% (IQR: 27-60%), postoperative 42% (IQR: 30-58%), post-discharge 28% (IQR: 20-42%), respectively. We had one thromboembolic complication and one hemorrhagic complication. The results indicated that appropriate platelet aggregation monitoring during multiple antiplatelet therapy prevents thromboembolic complications such as stent thrombosis. However, we also found that many patients demonstrated increased postoperative platelet aggregation inhibitory effects due to the postoperative continuation of the same multiple antiplatelet therapy that was used preoperatively. Conclusion: This study demonstrates that postoperative, continuous, oral antiplatelet therapy induces increased platelet aggregation inhibition effects, which may lead to hemorrhagic complications. Therefore, continued platelet aggregation monitoring after surgery may be important to allow for any necessary alterations to the therapeutic dose and regimen.

Delayed Complications Due to Polymer Coating Embolism after Endovascular Treatment.

There have recently been reports of patients who developed postprocedural symptoms or alterations due to delayed foreign body embolisms observed in imaging findings. Polymer coating of devices have been described as a possible cause of foreign body embolisms, manifesting in delayed granulomatous responses and exhibiting characteristic imaging findings. In four of 4,025 patients who underwent coil embolization in our hospital or its affiliated facilities, similar findings were observed. Delayed lesions appeared between 1 month and 1 year after the procedures. There was extensive edema in the perfusion area of the treated vessels. In two cases examined by contrast-enhanced magnetic resonance imaging, multiple solid enhancing lesions within vasogenic edema were observed. Biopsy revealed a membranous foreign body in a blood vessel with surrounding foreign body granuloma formation in 1 case. Because these findings are similar to those of cases reported previously, they were considered as a foreign body embolism due to coating separations from the devices. Polymer coating separation occurs most frequently from guidewires. Especially if a metal introducer is used, the risk of separation increases. Surgeons should carefully follow the manufacturers' instructions when they use these devices and should acknowledge and report any events that may occur. Although these complications are extremely rare, further studies are warranted of similar cases; and we should prepare and share information on these intravascular devices for wide-scale dissemination in the industry.

Histological and Transmission Electron Microscopy Results after Embolization with HydroSoft/HydroFrame Coils in Experimental Swine Aneurysm.

Coiling and clipping are standard treatment strategies for cerebral aneurysms. Regardless of the strategy used, recanalization may affect the patient's prognosis. The aim of this study was to histologically and morphologically compare the tissue proliferation after coil embolization using bare platinum coils versus second-generation hydrogel coils (HydroSoft/HydroFrame; MicroVention, Inc., Aliso Viejo, CA, USA). Endothelial-like cell proliferation was seen in both groups at 2 weeks after surgery. Macroscopic findings showed a tighter layer at 4 weeks in the hydrogel coil group, and histological and immunohistochemical findings revealed endothelial cell proliferation. This layer became much thicker and tighter at 4 weeks after surgery. Aneurysms treated with second-generation hydrogel coils may be more stable and have a lower incidence of recanalization than those treated with bare platinum coils because of the tight endothelial layer proliferation.

[Three Cases of Esophageal Submucosal Hematoma after Coiling for Unruptured Cerebral or Intracranial Aneurysms].

We report three cases of esophageal submucosal hematoma after treatment of unruptured intracranial aneurysms. All cases were in women with a mean age of 67.7 years. They were administered anti-platelet drugs before undergoing operations to deliver stents. All cases were administered general heparinization during the operation. All three cases developed sudden-onset hemoptysis or epigastric pain. The medical treatments included the temporary cessation or reduction of antiplatelet therapy and all cases were discharged with symptom cure and with the appearance of gastric intestinal fiber on computed tomography imaging. Esophageal submucosal hematoma has a good prognosis with medical therapy. We should consider the potential for esophageal submucosal hematoma after hemoptysis or epigastric pain after coiling of unruptured intracranial aneurysms that require antiplatelet or anticoagulant therapies.

Flow Diverter Therapy of a Giant Fusiform Vertebrobasilar Junction Aneurysm in a Child: Case Report.

The management of giant vertebrobasilar junction (VBJ) aneurysms is extremely challenging. Flow diverter (FD) therapy has become an important alternative to treat difficult intracranial aneurysms for both open surgery and conventional endovascular therapy. Herein, we report a rare case of a giant fusiform VBJ aneurysm in a child that is successfully treated with FD therapy.

Very delayed discontinuation of telescoped Pipeline embolization devices: a case report.

BACKGROUND: Flow diversion with the Pipeline embolization device (PED) is a widely accepted treatment modality for aneurysm occlusion. Previous reports have shown no recanalization of aneurysms on long-term follow-up once total occlusion has been achieved. CASE DESCRIPTION: We report on a 63-year-old male who had a large internal carotid artery cavernous segment aneurysm. Treatment with PED resulted in complete occlusion of the aneurysm. However, follow-up angiography at four years revealed recurrence of the aneurysm due to disconnection of the two PEDs placed in telescoping fashion. CONCLUSION: Herein, we present the clinico-radiological features and discuss the possible mechanisms resulting in the recanalization of aneurysms treated with flow diversion.

Patency of anterior choroidal artery after flow diverter deployment with assessment of magnetic resonance imaging follow-up.

PURPOSE: We aimed to analyse the patency rate of the anterior choroidal artery, and presented imaging and neurological findings, after deployment of a flow diverter in the anterior choroidal artery in the treatment of patients with intracranial aneurysms. METHODS: Among the 139 patients who underwent a flow diverter deployment from December 2012 to September 2017 in our hospital, there were 21 patients (15.1%) for whom their anterior choroidal artery was covered for the procedure with a flow diverter. The patients' age, sex, size of aneurysm and the presence or absence of an anterior choroidal artery occlusion, neurological findings and postoperative infarction in the anterior choroidal artery region were analysed retrospectively. RESULTS: The mean age of the six male and 15 female patients was 61.5 years (range 32-77 years). The mean maximal diameter of the aneurysms was 16.4 mm (range 10.0-29.4 mm). The anterior choroidal artery was patent in all 21 patients; however, a haemodynamic alteration in the anterior choroidal artery was detected in one patient. Postoperatively, hemiparesis was observed in two patients (9.5%) and a visual field defect in one patient (4.8%), both of which were the symptoms of infarction of the cortical branch of the middle cerebral artery or retinal artery ischaemia. However, no patients had symptoms due to ischaemia of the anterior choroidal artery confirmed with magnetic resonance imaging. CONCLUSIONS: In all patients who underwent flow diverter deployment, the anterior choroidal artery was patent and no ischaemia was detected in the imaging or evidenced by neurological findings. Therefore, flow diverter deployment in the anterior choroidal artery was considered to be a safe procedure.

Flow Diverter Therapy Using a Pipeline Embolization Device for 100 Unruptured Large and Giant Internal Carotid Artery Aneurysms in a Single Center in a Japanese Population.

Flow diverters (FDs) have been developed for intracranial aneurysms difficult to treat with conventional endovascular therapy and surgical clipping. We reviewed 94 patients with 100 large or giant unruptured internal carotid artery (ICA) aneurysms treated with Pipeline embolization device (PED) embolization from December 2012 to June 2017 at Juntendo University Hospital. The patients' mean age was 63.4 years (range, 19-88), and there were 90 women 89.4%. Aneurysm locations were: C4 (45), C3 (4), and C2 (51) in ICA segments. Mean aneurysm size and neck width were 16.9 ± 6.8 mm and 8.3 ± 4.4 mm, respectively, in 40 symptomatic and 60 asymptomatic aneurysms. Follow-up catheter angiographies of 85 patients with 90 aneurysms showed no filling in 62 aneurysms (68.9%), entry remnant in 16 (17.8%), subtotal filling in 11 (12.2), and total filling in 1 (1.1%) with a mean follow-up of 10.2 ± 5.6 months. In-stent stenosis occurred in 1 patient and parent artery occlusion in 2 during follow-up. Hemorrhagic complications occurred in 4 (4.3%): delayed aneurysm rupture (2) and intraparenchymal hemorrhage (2). Ischemic complications with neurological symptoms occurred in 2 (2.1%): very delayed device occlusion (1) and intraprocedural distal embolism (1). Eighteen patients (45%) showed improvement in pre-existing cranial nerve dysfunction because of the aneurysm's mass effect, 3 patients (7.5%) worsened. One patient died of systemic organ failure unassociated with the procedure. Morbidity and mortality rates were 4.3% and 1.1%, respectively. PED embolization for unruptured large and giant ICA aneurysms is safe and efficacious. Physicians should be observant of characteristic risks associated with FD therapy.

Transvenous Aneurysm Sac and Rupture Point Coil Embolization of Direct Carotid Cavernous Fistula after Pipeline Embolization.

A delayed aneurysm rupture after flow diverter therapy is a rare but serious complication. Due to the anatomical specificity, a delayed rupture of a carotid cavernous aneurysm may cause a direct carotid cavernous fistula (dCCF). We present a novel therapeutic approach for treatment of dCCF after flow diverter therapy using the Pipeline embolization device (PED). An 86-year-old woman suffered from dCCF after PED embolization. A microcatheter was advanced through the transvenous approach into the cavernous sinus (CS) and further inserted into the aneurysm sac via the rupture point. Coil embolization of both the aneurysm sac and a small part of the CS adjacent to the fistulous site could achieve not only the immediate aneurysm occlusion but also the rupture point obliteration with a small amount of coil mass in the CS.

Matrin3 binds directly to intronic pyrimidine-rich sequences and controls alternative splicing.

Matrin3 is an RNA-binding protein that is localized in the nuclear matrix. Although various roles in RNA metabolism have been reported for Matrin3, in vivo target RNAs to which Matrin3 binds directly have not been investigated comprehensively so far. Here, we show that Matrin3 binds predominantly to intronic regions of pre-mRNAs. Photoactivatable Ribonucleoside-Enhanced Cross-linking and Immunoprecipitation (PAR-CLIP) analysis using human neuronal cells showed that Matrin3 recognized pyrimidine-rich sequences as binding motifs, including the polypyrimidine tract, a splicing regulatory element. Splicing-sensitive microarray analysis showed that depletion of Matrin3 preferentially increased the inclusion of cassette exons that were adjacent to introns that contained Matrin3-binding sites. We further found that although most of the genes targeted by polypyrimidine tract binding protein 1 (PTBP1) were also bound by Matrin3, Matrin3 could control alternative splicing in a PTBP1-independent manner, at least in part. These findings suggest that Matrin3 is a splicing regulator that targets intronic pyrimidine-rich sequences.

Symptomatic Very Delayed Parent Artery Occlusion After Flow Diversion Stent Embolization.

Flow diversion stents (FDSs) are constructed from high-density braided mesh, which alters intra-aneurysmal hemodynamics and leads to aneurysm occlusion by inducing thrombus formation. Although there are potential complications associated with FDS embolization, one of the serious complications is the parent artery occlusion due to the in-stent thrombosis. A 72-year-old woman with a symptomatic giant fusiform aneurysm in the cavernous segment of ICA underwent single-layer pipeline embolization device (PED) embolization. Six-month and 1-year follow-up conventional angiographies showed the residual blood flow in the aneurysm. Two-year follow-up MRI showed the aneurysm sac shrinkage and the antiplatelet therapy was discontinued. The patient suffered from symptomatic parent artery occlusion due to the in-stent thrombosis, 4 months after antiplatelet therapy discontinuation. The patient with the incompletely occluded aneurysm after PED embolization should be given long-term antiplatelet therapy because of the risk of delayed parent artery occlusion.

Endovascular Therapy for Infectious Intracranial Aneurysm: A Report of Four Cases.

BACKGROUND: Infectious intracranial aneurysms (IIAs) are rare but can cause substantial morbidity and mortality. We aimed to re-evaluate the role of endovascular therapy for the treatment of IIAs. METHODS: This study is a retrospective review of patients diagnosed with IIAs and treated by endovascular therapy in our institutions over the past 13 years. RESULTS: Four patients were diagnosed with infectious endocarditis with a total of 5 IIAs. Three of the 4 patients had ruptured IIAs. Two presented with intracerebral hemorrhage, one with subarachnoid hemorrhage, and one with cerebral infarction. The distal middle cerebral artery (MCA) was the most common site, followed by the distal segment of the posterior cerebral artery. Three patients were treated by parent artery occlusion and one by direct aneurysm obliteration. There were no periprocedural complications. One IIA treated by direct aneurysm occlusion was recanalized within 1 year and required a second embolization. Outcomes were measured by the modified Rankin Scale on discharge: 2 patients scored 0, 1 patient scored 1, and 1 patient scored 3. CONCLUSION: IIAs located deep in the brain or on the peripheral MCA can be safely treated with endovascular therapy even when they are lying in the eloquent cortex.

Direct carotid-cavernous fistulas occurring during neurointerventional procedures.

This study shows the frequency and types of carotid-cavernous fistula (CCF) complications that occurred during endovascular treatment. Transarterial endovascular surgeries involving the anterior circulation were performed for 1071 cases at our hospitals during four years. CCFs occurred in nine of 1071 cases (0.8%). CCF risk factors were female sex (p=0.032), aneurysmal location in the paraclinoid portion (p<0.001), and use of a distal access catheter (DAC) (p<0.001). There were no significant correlations between CCF risk and procedure type (p=0.411-1.0) and balloon use or nonuse (p=0.492). Eighty-nine percent (eight of nine) of the CCFs occurred at the genu of a cavernous internal carotid artery (ICA). Two cases of CCF disappeared spontaneously. The shunt was decreased by balloon expansion in one case, no additional treatment was required in one case, and five cases required transarterial fistula coil embolization. It is necessary to remember that a CCF may occur especially in aneurysmal treatment using a DAC in a female patient. The DAC and the 0.035-inch guidewire should be kept proximal to the carotid siphon and not go beyond it. When we cannot avoid navigating beyond it, we should consider using a softer DAC. In the case of a CCF caused by a DAC, it may be cured spontaneously or is treatable by transarterial coil embolization.

Differences in tissue proliferation and maturation between Matrix2 and bare platinum coil embolization in experimental swine aneurysms.

BACKGROUND AND PURPOSE: Recanalization of post-embolization cerebral aneurysms remains a serious problem that influences treatment outcomes. Matrix2 is a bioactive, bio-absorbable, detachable coil that was developed to reduce the risk of recanalization. We examined the short-term efficacy of the Matrix2 coil system, and evaluated the temporal profile of tissue proliferation in a swine experimental aneurysm model compared with the bare platinum (BP) coil. MATERIALS AND METHODS: Thirty-six experimental aneurysms were created in 18 swine. All aneurysms were tightly packed with Matrix2 or BP coils. Comparative histologic and morphologic analyses were undertaken 1, 2 and 4 weeks post-embolization. RESULTS: Endothelial-like cells were observed partially lining the aneurysmal opening one week post-embolization with both coil types. At two and four weeks post-embolization, the aneurysms treated with Matrix2 coils had more extensive areas of organized thrombus than those packed with BP coils, but the numbers of functional proliferating endothelial cells identified by immunohistochemistry in the tissue were broadly comparable between the groups. Moreover, morphological analysis suggested there were more mature endothelial cells in aneurysms treated with bare platinum rather than Matrix2 coils. CONCLUSIONS: Our results indicate that aneurysms embolized with Matrix2 coils build thicker scaffolds for endothelialization, but this is not necessarily evidence of earlier tissue proliferation and maturation than those embolized with BP coils. Matrix2 coils may not be superior to BP coils for preventing aneurysmal recanalization after endovascular treatment of cerebral aneurysms.

Endovascular parent artery occlusion of proximal posterior cerebral artery aneurysms: a report of two cases.

We report two cases of proximal posterior cerebral artery (PCA) aneurysms treated with endovascular parent artery occlusion (PAO) with coils. In both cases, selective injection from the 4 F distal access catheter clearly showed the perforating arteries arising from the PCA. Case No 1, a 49-year-old woman, was successfully treated with preservation of a paramedian artery. Case No 2, a 54-year-old woman, was treated in the same manner. The patient underwent extensive thalamic infarction after the procedure because of paramedian artery occlusion. Endovascular PAO with coils is feasible for proximal PCA aneurysms; however, preservation of perforating arteries arising from the PCA is mandatory.

[Case Report of Cerebellar Vermis Arteriovenous Malformation Presenting with Hydrocephalus due to Aqueductal Stenosis].

A 56-year-old man complained of gait disturbance and confused thinking. Magnetic resonance imaging(MRI)revealed an arteriovenous malformation(AVM)of the cerebellar vermis(Spetzler-Martin grade IV)causing hydrocephalus. One dilated precentral cerebellar vein was compressing the aqueduct. After feeder embolization over 3 sessions using N-butyl cyanoacrylate(NBCA), the nidus was reduced to one-third in size. However, symptoms remained unimproved, and endoscopic third ventriculostomy(ETV)was performed. The third ventricle showed thinning of the floor, with a fenestration in part of the floor. Radiological findings and clinical symptoms improved, and the patient returned home after rehabilitation. The condition of the patient remained stable as of six months later. On angiography, the draining vein showed a pressure of 20 mmHg with no change in the residual AVM. Embolization alone achieved a reduction in nidus volume, but could not reduce venous pressure, and combination therapy including ETV proved necessary. Cases with hydrocephalus due to aqueductal stenosis by AVM are extremely rare. This pathology is discussed with reference to the literature.

Intercavernous sinus dural arteriovenous fistula treated with transvenous coil embolization: a case report.

The blood supply to the region of the cavernous sinus is provided by interconnecting branches of the internal and external carotid arteries, and it is from these vessels that dural arteriovenous fistulas (DAVFs) arise. It is very rare that DAVFs are located at the intercavernous sinuses region; in this case, a proper localization of the fistulous site is of extreme importance in order to successfully eliminate the disease. Here, we describe a case of a 65-year-old female with intercavernous sinus DAVF. A complete obliteration of the fistulous points was performed by coil embolization through a transvenous approach.

Treatment results of endosaccular coil embolization of asymptomatic unruptured intracranial aneurysms in elderly patients.

BACKGROUND AND PURPOSE: We report the results of endosaccular coil embolization of asymptomatic unruptured intracranial aneurysms (UIAs) in elderly patients (≥65 years). MATERIALS: There were 375 elderly patients with 400 asymptomatic UIAs. Patients were divided into two groups: group A included patients aged 65-74 years and group B patients aged ≥75 years. RESULTS: Endovascular procedures were completed in 97.8% of patients. Immediate anatomical outcomes showed complete occlusion in 53.7%, residual neck in 18.9%, and residual aneurysm in 27.4%. Anatomical follow-ups (mean 36.3±28.1 months) were unchanged in 55.7%, improved in 22.6%, minor recurrence in 11.5%, and major recurrence in 10.2%. Procedure related complications occurred in 31 patients (8.3%). 15 patients had ischemic and 10 hemorrhagic complications. Retreatments were performed in 16 patients (4.3%). Among 366 patients technically completed, 363 (99.2%) showed a favorable clinical outcome (modified Rankin Scale (mRS) score <1) at 30 days. The remaining three patients showed a worsening of mRS >0 at 30 days. The latest clinical follow-up outcomes showed: mRS score 0 in 362 patients; mRS score 1 in one; mRS score 3 in one; mRS score 4 in one; and mRS score 5 in one patient. Permanent morbidity and mortality rates were 1.1% and 0%, respectively. There were no statistically significant differences in gender, comorbidities, aneurysm size, neck width, dome-to-neck ratio, immediate anatomical outcomes, anatomical follow-up outcomes, or procedure related complications between the groups. CONCLUSIONS: Endosaccular coil embolization is safe and feasible for elderly patients with asymptomatic UIAs. Old age itself should not be a contraindication.

Radiological changes in infantile dissecting anterior communicating artery aneurysm treated endovascularly. A case report and five-year follow-up.

Intracranial aneurysms are extremely rare in infants, and to our knowledge only seven infants treated for ruptured spontaneous dissecting aneurysms have been reported. Good outcomes have been achieved with endovascular treatment of infantile aneurysm. We the endovascular treatment of a one-month-old girl for ruptured dissecting aneurysm located in the anterior communicating artery, and the unique radiological changes that were observed during the perioperative and follow-up periods. These changes suggest that blood coagulation and fibrinolytic response play a part in the repair and healing processes of dissecting aneurysms. Careful neuroradiological surveys are needed for pediatric dissecting aneurysms treated endovascularly.