A novel SREBF1::NACC1 gene fusion in an unclassifiable intracranial tumour.

A 39-year-old man had an intracranial tumour without infiltration into the surrounding cerebral tissue. The tumour recurred seven times in 11 years but maintained a well-demarcated character. Histopathological examination of the 4th surgical specimens showed nests of tumour cells surrounding small blood vessels. The tumour cells harboured amphophilic cytoplasm and small round nuclei with fine chromatin, and perinuclear haloes and clear borders were frequently observed, which was unclassifiable histology. By the Deutsches Krebsforschungszentrum methylation classifier, the tumour was not classified into any of the methylation classes. mRNA sequencing identified a novel SREBF1::NACC1 gene fusion. This intracranial tumour could be a novel tumour entity with NACC1 rearrangement showing characteristic histological and diagnostic imaging findings.

Lack of Association between Seropositivity of Vasculopathy-Related Viruses and Moyamoya Disease.

OBJECTIVES: Although the association between genetic factors, such as RNF213 mutations, and moyamoya disease (MMD) has been well investigated, environmental factors are largely undetermined. Thus, we aimed to examine whether viral infection increases the risk of MMD. MATERIALS AND METHODS: To eliminate the effect of presence or absence of the RNF213 p.R4810K mutation, the entire study population was positive for this mutation. We collected whole blood from 111 patients with MMD (45 familial and 66 sporadic cases) and 67 healthy volunteers, and we measured the immunoglobulin G titer of 11 viruses (cytomegalovirus, varicella-zoster virus, measles virus, rubella virus, herpes simplex virus, mumps virus, Epstein-Barr virus, human parvovirus B19, human herpesvirus 6 [HHV6], human herpesvirus 8, and John Cunningham virus) that were presumed to be associated with vasculopathy using the enzyme-linked immunosorbent assay. Positivity for past viral infection was determined by cut-off values obtained from previous reports and the manufacturer's instructions, and the positive rate was compared between cases and age- and sex-matched controls. We performed familial case-specific and sporadic case-specific analyses, as well as a case-control analysis. RESULTS: There was no significant difference in the positive rate between the case group and the control group in any of the analyses. A significant difference was only observed in the combined case-control analysis for HHV6 (p = 0.046), but the viral antibody-positive rate in control individuals was higher than in MMD cases. CONCLUSIONS: Our cross-sectional study suggest that the investigated 11 viruses including HHV6 are unlikely to have an impact on MMD development.

Factors associated with the new appearance of cerebral microbleeds after endovascular treatment for unruptured intracranial aneurysms.

PURPOSE: Endovascular treatment of unruptured intracranial aneurysms may increase cerebral microbleeds (CMBs) in postprocedural T2*-weighted MRIs, which may be a risk for future intracerebral hemorrhage. This study examined the characteristics of postprocedural CMBs and the factors that cause their increase. METHODS: The patients who underwent endovascular treatment for unruptured intracranial aneurysms from April 2016 to February 2018 were retrospectively analyzed. Treatment techniques for endovascular treatment included simple coiling, balloon-assisted coiling, stent-assisted coiling, or flow diverter placement. To evaluate the increase in CMBs, a head MRI including diffusion-weighted imaging and T2*-weighted MRIs was performed on the preprocedural day; the first postprocedural day; and at 1, 3, and 6 months after the procedure. RESULTS: Among the 101 aneurysms that were analyzed, 38 (37.6%) showed the appearance of new CMBs. In the multivariate analysis examining the causes of the CMB increases, chronic kidney disease, a higher number of preprocedural CMBs, and a higher number of diffusion-weighted imaging-positive lesions on the first postprocedural day were independent risk factors. Furthermore, a greater portion of the increased CMBs was found in cortical and subcortical lesions of the treated vascular perfusion area within 1 month after the procedure. CONCLUSION: In endovascular treatment for unruptured intracranial aneurysms, CMBs tended to increase in patients with small vessel disease before the procedure, and it was also implicated in hemorrhagic changes after periprocedural microinfarction.

Ruptured aneurysm of the posterior inferior cerebellar artery communicating artery: A case report.

We report a case of a ruptured aneurysm of the posterior inferior cerebellar artery (PICA) communicating artery, which is an extremely rare condition, with only 10 other cases reported in the literature. We repaired the aneurysm by clipping combined with occipital artery-PICA (cortical segment) bypass. This surgical method reduces hemodynamic stress and may prevent recurrence or new occurrence of aneurysms in this region. We recommend this method for repair of instances of PICA communicating artery aneurysm rupture.

Increased abundance of Ruminococcus gnavus in gut microbiota is associated with moyamoya disease and non-moyamoya intracranial large artery disease.

Moyamoya disease (MMD) is a rare cerebrovascular disease endemic in East Asia. The p.R4810K mutation in RNF213 gene confers a risk of MMD, but other factors remain largely unknown. We tested the association of gut microbiota with MMD. Fecal samples were collected from 27 patients with MMD, 7 patients with non-moyamoya intracranial large artery disease (ICAD) and 15 control individuals with other disorders, and 16S rRNA were sequenced. Although there was no difference in alpha diversity or beta diversity between patients with MMD and controls, the cladogram showed Streptococcaceae was enriched in patient samples. The relative abundance analysis demonstrated that 23 species were differentially abundant between patients with MMD and controls. Among them, increased abundance of Ruminococcus gnavus > 0.003 and decreased abundance of Roseburia inulinivorans < 0.002 were associated with higher risks of MMD (odds ratio 9.6, P = 0.0024; odds ratio 11.1, P = 0.0051). Also, Ruminococcus gnavus was more abundant and Roseburia inulinivorans was less abundant in patients with ICAD than controls (P = 0.046, P = 0.012). The relative abundance of Ruminococcus gnavus or Roseburia inulinivorans was not different between the p.R4810K mutant and wildtype. Our data demonstrated that gut microbiota was associated with both MMD and ICAD.

Symptomatic Cavernous Internal Carotid Artery Aneurysm Complicated by Simultaneous Rapid Growth of the Intra-aneurysmal and Parent Artery Thromboses.

Cavernous internal carotid artery (ICA) aneurysm complicated by simultaneous and spontaneous formation of thromboses in the aneurysm and the parent artery is a rare clinical condition. Although the majority of patients have good outcomes, some patients experience severe ischemic stroke. Here, we report a case of symptomatic large cavernous ICA aneurysm complicated by rapid growth of an intra-aneurysmal thrombosis with simultaneous parent artery thrombosis. A 68-year-old female presented with sudden-onset diplopia, right ptosis, right conjunctival hyperemia, and paresthesia of the right face. Magnetic resonance imaging (MRI) and digital subtract angiography (DSA) revealed the presence of a large partially thrombosed aneurysm in the cavernous portion of the right ICA. We planned endovascular embolization using a flow-diverting (FD) stent. Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel was started 2 weeks prior to treatment. Although the neurological state was stable, DSA conducted on the day of the endovascular treatment showed rapid growth of an intra-aneurysmal thrombosis and de novo thrombosis in the parent artery. Direct aspiration was performed via a distal support catheter with proximal blood flow arrest using a balloon-guide catheter, and the FD stent was successfully deployed. The patient's symptoms improved postoperatively and DSA obtained 12 months after the procedure confirmed complete occlusion of the aneurysm. Although the exact mechanism of simultaneous thrombosis formation of the aneurysm and its parent artery remains unclear, it is important to recognize that rapid growth of the thrombosis increases the risk of ischemic stroke.

Treatment of Aneurysms in Persistent Primitive Trigeminal Arteries with Stent-Assisted Coil Embolization.

Objective: Persistent primitive trigeminal artery (PPTA) is a rare condition in which a fetal carotid-basilar anastomosis persists into adulthood. PPTA aneurysms often necessitate endovascular treatment and adjunctive techniques, such as stent- or balloon-assisted techniques, are sometimes selected. This case report describes two women in their sixties with unruptured right PPTA aneurysms who underwent stent-assisted coil embolization procedures, with consideration of the anatomical features in each case. Case Presentations: One patient presented with an aneurysm at the bifurcation of the PPTA and the basilar artery (BA), which was classified as Saltzman type 1 with a hypoplastic vertebral artery (VA)-BA system. A stent was deployed from the BA to the PPTA to cover the neck of the aneurysm and coil embolization was performed. The second patient presented with an aneurysm at the bifurcation of the PPTA and the internal carotid artery (ICA), which was classified as Saltzman type 2 with a hypoplastic VA-BA system. A stent was deployed from the PPTA to the petrous segment of the ICA covering the neck of the aneurysm and coil embolization was performed. In both patients, the 1-year follow-up digital subtraction angiography (DSA) showed that the aneurysms had not recurred. Conclusion: The PPTA aneurysms were successfully treated with stent-assisted coil embolization. The treatment strategy should be devised in accordance with both the lesion site and the PPTA variant.

Clopidogrel response predicts thromboembolic events associated with coil embolization of unruptured intracranial aneurysms: A prospective cohort study.

OBJECTIVE: Periprocedural thromboembolic events are a serious complication associated with coil embolization of unruptured intracranial aneurysms. However, no established clinical rule for predicting thromboembolic events exists. This study aimed to clarify the significance of adding preoperative clopidogrel response value to clinical factors when predicting the occurrence of thromboembolic events during/after coil embolization and to develop a nomogram for thromboembolic event prediction. METHODS: In this prospective, single-center, cohort study, we included 345 patients undergoing elective coil embolization for unruptured intracranial aneurysm. Thromboembolic event was defined as the occurrence of intra-procedural thrombus formation and postprocedural symptomatic cerebral infarction within 7 days. We evaluated preoperative clopidogrel response and patients' clinical information. We developed a patient-clinical-information model for thromboembolic event using multivariate analysis and compared its efficiency with that of patient-clinical-information plus preoperative clopidogrel response model. The predictive performances of the two models were assessed using area under the receiver-operating characteristic curve (AUC-ROC) with bootstrap method and compared using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: Twenty-eight patients experienced thromboembolic events. The clinical model included age, aneurysm location, aneurysm dome and neck size, and treatment technique. AUC-ROC for the clinical model improved from 0.707 to 0.779 after adding the clopidogrel response value. Significant intergroup differences were noted in NRI (0.617, 95% CI: 0.247-0.987, p < .001) and IDI (0.068, 95% CI: 0.021-0.116, p = .005). CONCLUSIONS: Evaluation of preoperative clopidogrel response in addition to clinical variables improves the prediction accuracy of thromboembolic event occurrence during/after coil embolization of unruptured intracranial aneurysm.

Intracranial Subdural Abscess Caused by Actinomyces meyeri Related to Dental Treatment: A Case Report.

Intracranial subdural abscess is a rare condition. Although brain abscess is often reported in relation to dental infection, reports of intracranial subdural abscess are few. Actinomyces spp. forms part of the normal flora of the oral, gastrointestinal, and genital tract, and is rarely the cause of intracranial infection; moreover, the pathogen Actinomyces meyeri is very rare. We report an exceptional case of intracranial subdural abscess caused by A. meyeri and related to dental treatment. A 57-year-old woman initially presented with a 5-day history of headache. Because left arm numbness and weakness became apparent, she was admitted to our department. She had a history of hypertension and dental problems requiring tooth extractions. Diffusion-weighted imaging (DWI) showed a 1-cm right convexity hyperintense mass above the postcentral gyrus. A post-gadolinium T1-weighted image showed a thin hypointense area with peripheral rim enhancement in the right subdural space that appeared to partially thicken in the same location as the DWI-positive mass. She underwent emergent navigation-guided drainage and 4 mL of pus was obtained. Postoperatively, left arm numbness and weakness disappeared. Cultures showed growth of A. meyeri and Fusobacterium nucleatum. She was started on intravenous penicillin G and metronidazole. After a 4-week course of the intravenous antibiotics, her headache gradually improved and the abscess in the subdural space subsided. To our best knowledge this is the first case report of intracranial subdural abscess caused by A. meyeri associated with dental treatment.

Long-term Outcomes After Intraprocedural Aneurysm Rupture During Coil Embolization of Unruptured Intracranial Aneurysms.

BACKGROUND: The long-term outcomes of patients with intraprocedural aneurysm rupture (IPR) during endovascular coiling of unruptured intracranial aneurysms (UIAs) remain unclear. We investigated the long-term outcomes and predictors of neurological outcomes in patients who sustained IPR during coil embolization of UIAs. METHODS: We retrospectively analyzed the medical record of 312 untreated UIAs in 284 patients who underwent endovascular coiling between April 2013 and July 2018. RESULTS: The mean follow-up period for the entire cohort was 25.6 months. Twelve patients (3.8%) experienced IPR. The mean aneurysm size in the IPR cohort was significantly smaller than that in the no-IPR cohort (P = 0.045). The IPR cohort had a higher percentage of earlier subarachnoid hemorrhage from another aneurysm (P = 0.019), anterior communicating artery (AComA) aneurysm (P < 0.001), and basilar artery (BA) aneurysm (P = 0.022) than the no-IPR cohort. Neurologic deterioration was observed in 3 patients. The morbidity and mortality rates of the IPR cohort were 25% and 8.3%, respectively. Patients with IPR during coil embolization for AComA aneurysm did not develop neurological deterioration. Two of the 3 patients (66.7%) with a BA aneurysm had neurological deterioration. The proportion of patients with an mRS score of 0-2 at the last follow-up did not differ between the 2 cohorts (P = 0.608). CONCLUSIONS: The proportion of functionally independent patients did not differ between patients with and without IPR. Patients with BA aneurysms who developed an IPR tended to exhibit more unfavorable clinical courses than patients with AcomA aneurysms.

A Case of Posterior Reversible Encephalopathy Syndrome After Surgical Clipping of Unruptured Cerebral Aneurysm.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is characterized by reversible edematous lesions on imaging examinations, along with symptoms of altered consciousness disorder and seizures. Various factors associated with PRES have been reported. However, we encountered a very rare case that developed after clipping surgery for unruptured cerebral aneurysm. CASE DESCRIPTION: A 74-year-old man with a history of hypertension presented with an unruptured right middle cerebral artery aneurysm and underwent cranial clipping surgery. After surgery, he developed consciousness disorder and epilepsy after delayed awakening from general anesthesia. Radiological examinations revealed multiple edematous lesions, strongly suggesting PRES, and excluding asymmetry consistent with the area of craniotomy. With conservative treatment, symptoms and radiological findings almost disappeared. Symptoms and imaging findings remaining at the area of craniotomy were attributed to the severe difference in cerebral perfusion pressure due to craniotomy. CONCLUSIONS: Based on the literature, this case was considered to represent PRES caused by rapid blood pressure fluctuations accompanying general anesthesia for clipping surgery. Practitioners must keep PRES in mind as a rare complication after clipping for unruptured cerebral aneurysms. PRES developing after craniotomy shows unilaterality and may become severe in the craniotomy area and leave sequelae.

Thrombosis of Large Aneurysm Induced by Flow-Diverter Stent and Dissolved by Direct Factor Xa Inhibitor.

BACKGROUND: Antiplatelet agents are typically administered before and after treatment using flow-diverter stents (FDS) to prevent thrombotic complications, but the effects of anticoagulants are unclear. We present a patient with a giant aneurysm treated with an FDS. The thrombus within the aneurysm was dissolved when a direct factor Xa inhibitor was administered to treat lower limb venous thrombosis that occurred secondary to steroid use. CASE DESCRIPTION: A 60-year-old woman with a 30-mm giant thrombosed aneurysm in the cavernous segment of the right internal carotid artery presenting with headache and right abducens nerve palsy was treated by placing an FDS. Diplopia and increased pain in her right eye appeared on postoperative day 7, and both were alleviated by continuous oral administration of prednisolone. Angiography 3 months postoperatively revealed that the aneurysm thrombosis had progressed, and there were signs of healing. However, at the same time, lower limb venous thrombosis occurred, which was treated by continuous edoxaban. Six months after surgery, her headaches worsened and angiography showed that the aneurysm was again contrast enhanced and that the thrombus within the aneurysm had dissolved. After discontinuing edoxaban 9 months after surgery, the aneurysmal thrombosis had again rapidly progressed. CONCLUSIONS: Administration of a direct factor Xa inhibitor during healing after placing an FDS may cause dissolution of an existing thrombus; therefore factor Xa inhibitors must be used with caution.

Factors Associated with Postprocedural Diffusion-Weighted Imaging-Positive Lesions in Endovascular Treatment for Unruptured Cerebral Aneurysms.

BACKGROUND: In endovascular treatment for cerebral aneurysms, the appearance of asymptomatic thromboembolic lesions detected by postprocedural diffusion-weighted imaging (DWI) can be a surrogate marker for estimating the potential risk of symptomatic thromboembolism. The aim of this study was to clarify factors associated with postprocedural DWI-positive lesions in endovascular treatment for unruptured cerebral aneurysms. METHODS: Patients with untreated unruptured cerebral aneurysms undergoing endovascular treatment were consecutively enrolled. Treatment techniques were classified into simple coiling, balloon-assisted coiling, stent-assisted coiling, and flow-diverter placement. Head magnetic resonance imaging was performed within 3 months before and 24 hours after the procedure to assess the appearance of DWI-positive lesions. RESULTS: Among 376 aneurysms in 355 patients that were analyzed, 232 (61.7%) had postprocedural DWI-positive lesions. In univariate analyses, age (P = 0.001), dome size (P < 0.001), neck size (P < 0.001), treatment technique (P = 0.029), and total procedural time (P < 0.001) were significantly associated with postprocedural DWI-positive lesions. In the multiple logistic regression model, older age (odds ratio, 1.33; 95% confidence interval, 1.10-1.60; P = 0.003; per decade), flow-diverter placement (odds ratio, 4.93; 95% confidence interval, 1.33-20.92; P = 0.016; compared with simple coiling), and longer procedural time (odds ratio, 1.66; 95% confidence interval, 1.26-2.21; P < 0.001; per hour) were associated with postprocedural DWI-positive lesions. CONCLUSIONS: Older age, flow-diverter placement, and longer procedural time were associated with postprocedural DWI-positive lesions in endovascular treatment for unruptured cerebral aneurysms.

A Visual Task Management Application for Acute Ischemic Stroke Care.

Background: To maximize the effect of intravenous (IV) thrombolysis and/or endovascular therapy (EVT) for acute ischemic stroke (AIS), stroke centers need to establish a parallel workflow on the basis of a code stroke (CS) protocol. At Kokura Memorial Hospital (KMH), we implemented a CS system in January 2014; however, the process of information sharing within the team has occasionally been burdensome. Objective: To solve this problem using information communication technology (ICT), we developed a novel application for smart devices, named "Task Calc. Stroke" (TCS), and aimed to investigate the impact of TCS on AIS care. Methods: TCS can visualize the real-time progress of crucial tasks for AIS on a dashboard by changing color indicators. From August 2015 to March 2017, we installed TCS at KMH and recommended its use during normal business hours (NBH). We compared the door-to-computed tomography time, the door-to-complete blood count (door-to-CBC) time, the door-to-needle for IV thrombolysis time, and the door-to-puncture for EVT time among three treatment groups, one using TCS ("TCS-based CS"), one not using TCS ("phone-based CS"), and one not based on CS ("non-CS"). A questionnaire survey regarding communication problems was conducted among the CS teams at 3 months after the implementation of TCS. Results: During the study period, 74 patients with AIS were transported to KMH within 4.5 h from onset during NBH, and 53 were treated using a CS approach (phone-based CS: 26, TSC-based CS: 27). The door-to-CBC time was significantly reduced in the TCS-based CS group compared to the phone-based CS group, from 31 to 19 min (p = 0.043). Other processing times were also reduced, albeit not significantly. The rate of IV thrombosis was higher in the TCS-based CS group (78% vs. 46%, p = 0.037). The questionnaire was correctly filled in by 34/38 (89%) respondents, and 82% of the respondents felt a reduction in communication burden by using the TCS application. Conclusions: TCS is a novel approach that uses ICT to support information sharing in a parallel CS workflow in AIS care. It shortens the processing times of critical tasks and lessens the communication burden among team members.

Dural and Pial Arteriovenous Fistulas Connected to the Same Drainer in the Middle Cranial Fossa: A Case Report.

BACKGROUND: Dural arteriovenous fistulas (AVFs) in the middle cranial fossa are rare. Pial AVFs are similarly rare but differ from dural AVFs in that they derive their arterial supply from pial or cortical arterial vessels and do not lie within the intradural region. We report an extremely rare case of dural and pial AVF connected to the same drainer in the middle cranial fossa. CASE DESCRIPTION: In a 58-year-old man with a subcortical hemorrhage in the right temporal lobe, digital subtraction angiography showed a dural AVF in the middle cranial fossa fed by the middle meningeal artery (MMA) and draining into the sphenopetrosal vein. A combination with a small pial AVF connected to the same sphenopetrosal vein was suspected. Open surgery was performed to directly observe the shunt points. Transarterial indocyanine green (ICG) angiography using the MMA via the superficial temporal artery on a skin flap was performed to repeatedly and distinctly evaluate the dural shunt points and to prevent cerebral thromboembolism. Although the dural supply was completely disconnected, the sphenopetrosal vein remained arterialized. ICG angiography revealed pial AVF, which was fed by the cortical arteries draining into the same drainer. The pial supply was completely disconnected, and disappearance of the dural and pial AVF was confirmed. CONCLUSIONS: We report an extremely rare case of dural and pial AVF connected to the same drainer in the middle cranial fossa. To our knowledge, this is the first such case report described in the literature.

Improving treatment times for patients with in-hospital stroke using a standardized protocol.

BACKGROUND: Previous reports have shown significant delays in treatment of in-hospital stroke (IHS). We developed and implemented our IHS alert protocol in April 2014. We aimed to determine the influence of implementation of our IHS alert protocol. METHODS: Our implementation processes comprise the following four main steps: IHS protocol development, workshops for hospital staff to learn about the protocol, preparation of standardized IHS treatment kits, and obtaining feedback in a monthly hospital staff conference. We retrospectively compared protocol metrics and clinical outcomes of patients with IHS treated with intravenous thrombolysis and/or endovascular therapy between before (January 2008-March 2014) and after implementation (April 2014-December 2016). RESULTS: Fifty-five patients were included (pre, 25; post, 30). After the implementation, significant reductions occurred in the median time from stroke recognition to evaluation by a neurologist (30 vs. 13.5min, p<0.01) and to first neuroimaging (50 vs. 26.5min, p<0.01) and in the median time from first neuroimaging to intravenous thrombolysis (45 vs. 16min, p=0.02). The median time from first neuroimaging to endovascular therapy had a tendency to decrease (75 vs. 53min, p=0.08). There were no differences in the favorable outcomes (modified Rankin scale score of 0-2) at discharge or the incidence of symptomatic intracranial hemorrhage between the two periods. CONCLUSION: Our IHS alert protocol implementation saved time in treating patients with IHS without compromising safety.

Serial Myocardial Imaging after a Single Dose of Thallium-201.

Although thallium-201 exercise scintigraphy has been established for the detection of myocardial ischemia and viability, little is known regarding the myocardial thallium-201 kinetics during angioplasty. Herein, we report a 77-year-old man with angina pectoris, in whom serial myocardial imaging after a single dose of thallium-201 was helpful in identifying not only the culprit lesion and myocardial viability, but also the dynamic changes in myocardial perfusion during angioplasty. Thallium-201 images after exercise showed a perfusion defect in the inferior wall, with a trivial redistribution 3 hours after the exercise and a marked improvement 24 hours later. Coronary angiography, performed 27 hours after exercise scintigraphy, showed severe stenosis in the right coronary artery. Guidewire crossing of the lesion interrupted the antegrade flow, which was restored after balloon dilation and stent implantation. Thallium-201 images, 2 hours after angioplasty (i.e., 30 hours after exercise), showed a decreased tracer uptake in the inferior wall, which improved the next day (i.e., 48 hours after exercise). Cardiac biomarkers were negative in the clinical course.