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Background Isolated basilar artery dissection (IBAD) is a rare but important cause of ischemic stroke. Anti-thrombotic therapy is often used to treat IBAD-related ischemic stroke, but selected cases might need more aggressive treatment. There is no previous report of emergent stenting for IBAD-related ischemic stroke after intravenous thrombolysis. Case presentation A 53-year-old Japanese woman was admitted to our hospital with disturbance of consciousness, right hemiplegia, severe dysarthria, and total gaze paralysis. Brain magnetic resonance imaging revealed no ischemic lesion, but magnetic resonance angiography showed stenosis in the basilar artery. After initiation of intravenous thrombolysis, her neurological symptoms dramatically improved. Five hours later, however, her symptoms deteriorated again. Cerebral angiography showed IBAD. Emergent stenting was successfully performed. At 90 days after stroke onset, she had no significant disability, with a modified Rankin scale score of 1. Conclusions Emergent stenting can be an effective treatment for patients with IBAD-related ischemic stroke who are resistant to IV-rtPA.

Postoperative rebleeding (PR) is one of the most severe complications of endoscopic surgery, often performed to remove spontaneous intracerebral hemorrhage (sICH). However, the risk factors for PR remain unclear. This study retrospectively investigated whether increased preoperative plasma plasmin-α2-plasmin inhibitor complex (PIC) levels, indicating activation of fibrinolysis, are associated with PR. A total of 101 patients underwent endoscopic surgery to evacuate sICH at our institution from January 2010 to June 2019, and 79 patients who underwent examinations of plasma PIC levels at admission with available radiographical data were included. Correlations between PR and increased plasma PIC levels were retrospectively evaluated. PR occurred in eight patients (10.1%), and high PIC levels (≥ 4 or 6 μg/ml) were significantly associated with PR. The sensitivities employing high PIC levels of ≥ 4 μg/ml and ≥ 6 μg/ml were both 0.63, and the specificities using the same PIC levels were 0.86 and 0.92, respectively. Multivariable analyses showed that high plasma PIC levels of ≥ 4 μg/ml (odds ratio (OR), 12.77; 95% confidence interval (CI), 1.65–98.77; p = 0.02) or ≥ 6 μg/ml (OR, 18.33; 95% CI, 2.32–144.82; p = 0.006) were independent predictors of PR. This study found that increased plasma PIC levels were associated with PR following the endoscopic evacuation of sICHs, indicating that increased plasma PIC levels could be potentially used to predict PR. Further studies are needed to establish new surgical strategies and adjuvant treatments to improve surgical outcomes in patients with sICH prone to PR.

Introduction: Mechanical thrombectomy (MT) for acute ischemic stroke has become a standard therapy, and the recanalization rate has significantly improved. However, some cases of unsuccessful recanalization still occur. We aimed to clarify patient factors associated with unsuccessful recanalization after MT for acute ischemic stroke. Methods: This was a single-center, retrospective study of 119 consecutive patients with anterior circulation acute ischemic stroke who underwent MT at our hospital between April 2015 and March 2019. Successful recanalization after MT was defined as modified Treatment in Cerebral Ischemia (mTICI) grade 2b or 3, and unsuccessful recanalization was defined as mTICI grades 0–2a. Several factors were analyzed to assess their effect on recanalization rates. Results: Successful recanalization was achieved in 88 patients (73.9%). The univariate analysis showed that female sex (38.6 vs. 67.7%, p = 0.007), a history of hypertension (53.4 vs. 83.9%, p = 0.003), and a longer time from groin puncture to recanalization (median 75 vs. 124 min, p < 0.001) were significantly associated with unsuccessful recanalization. The multivariate analysis confirmed that female sex (OR 3.18; 95% CI 1.12–9.02, p = 0.030), a history of hypertension (OR 4.84; 95% CI 1.32–17.8, p = 0.018), M2–3 occlusion (OR 4.26; 95% CI 1.36–13.3, p = 0.013), and the time from groin puncture to recanalization (per 10-min increase, OR 1.22; 95% CI 1.09–1.37, p < 0.001) were independently associated with unsuccessful recanalization. Conclusion: Female sex and a history of hypertension might be predictors of unsuccessful recanalization after MT for anterior circulation acute ischemic stroke. Further studies are needed to fully evaluate predictors of recanalization.

Background Thrombosis is a dynamic process, and a thrombus undergoes physical and biochemical changes that may alter its response to reperfusion therapy. This study assessed whether thrombus age influenced reperfusion quality and outcomes after mechanical thrombectomy for cerebral embolism. Methods We retrospectively evaluated 185 stroke patients and thrombi that were collected during mechanical thrombectomy at three stroke centers. Thrombi were pathologically classified as fresh or older based on their granulocytes' nuclear morphology and organization. Thrombus components were quantified, and the extent of NETosis (the process of neutrophil extracellular trap formation) was assessed using the density of citrullinated histone H3-positive cells. Baseline patient characteristics, thrombus features, endovascular procedures, and functional outcomes were compared according to thrombus age. Results Fresh thrombi were acquired from 43 patients, and older thrombi were acquired from 142 patients. Older thrombi had a lower erythrocyte content (p Conclusion An older thrombus delays reperfusion after mechanical thrombectomy for ischemic stroke. Adding therapies targeting thrombus maturation may improve the efficacy of mechanical thrombectomy.

Background and Purpose: To date, the incidence of intracranial and spinal arteriovenous shunts has not been thoroughly investigated. We aimed to clarify recent trends in the rates of intracranial and spinal arteriovenous shunts in Japan. Methods: We conducted multicenter hospital-based surveillance at 8 core hospitals in Okayama Prefecture between April 1, 2009 and March 31, 2019. Patients who lived in Okayama and were diagnosed with cerebral arteriovenous malformations, dural arteriovenous fistulas (DAVFs), or spinal arteriovenous shunts (SAVSs) were enrolled. The incidence and temporal trends of each disease were calculated. Results: Among a total of 393 cranial and spinal arteriovenous shunts, 201 (51.1%) cases of DAVF, 155 (39.4%) cases of cerebral arteriovenous malformation, and 34 (8.7%) cases of SAVS were identified. The crude incidence rates between 2009 and 2019 were 2.040 per 100 000 person-years for all arteriovenous shunts, 0.805 for cerebral arteriovenous malformation, 1.044 for DAVF, and 0.177 for SAVS. The incidence of all types tended to increase over the decade, with a notable increase in incidence starting in 2012. Even after adjusting for population aging, the incidence of nonaggressive DAVF increased 6.0-fold while that of SAVS increased 4.4-fold from 2010 to 2018. Conclusions: In contrast to previous studies, we found that the incidence of DAVF is higher than that of cerebral arteriovenous malformation. Even after adjusting for population aging, all of the disease types tended to increase in incidence over the last decade, with an especially prominent increase in SAVSs and nonaggressive DAVFs. Various factors including population aging may affect an increase in DAVF and SAVS.

Carotid revascularization may be considered for severe stenosis, but its use for symptomatic mild stenosis (50%) with vulnerable plaque or ulcer remains uncertain. The characteristics of patients with symptomatic mild stenosis who underwent revascularization are reviewed.The subjects of this study were 18 patients with symptomatic mild stenosis (50%) on angiography from among 175 patients who underwent revascularization in our department. The plaques were evaluated by black-blood magnetic resonance imaging (BB-MRI) and ultrasonography (US) and classified into 2 types: type 1 (n = 15), a lesion with an ulcer or mobile plaque or thrombosis on angiography or US; and type 2 (n = 3), a lesion without any of the above. Fourteen patients underwent carotid endarterectomy (CEA), and 4 patients underwent carotid artery stenting.The stenosis on angiography was 27.2% ± 10.7 (5%-41%), and the area carotid artery stenosis rate on US was 69.8 ± 14.5% (44.5%-97%). The stenosis rate of these 2 methods was not at all correlated. In type 1 plaque that underwent CEA, 10 of 11 patients had vulnerable plaque by histopathology, and 1 patient had thrombus on the plaque by operative findings. In type 2 plaque that underwent CEA, all patients had vulnerable plaque by histopathology. During the follow-up period, none of the patients had restenosis or stroke.The findings of US and BB-MRI in patients with symptomatic mild stenosis (50%) on angiography are important for determining treatment. If BB-MRI or US shows the findings of vulnerable plaque in mild stenosis, surgical treatment may be considered for these patients.

Indocyanine green (ICG) emits fluorescence in the far-red domain under light excitation. ICG video angiography (ICG-VA) has been established as a useful method to evaluate blood flow in the operative field. We report the usefulness of ICG-VA for Sylvian fissure dissection in patients with subarachnoid hemorrhage (SAH). Subjects comprised 7 patients who underwent ICG-VA before opening the Sylvian fissure during neck clipping for ruptured cerebral aneurysm. We observed contrasted Sylvian veins before opening the Sylvian fissure using surgical microscopes. This procedure was termed "Sylvian ICG". We observed ICG fluorescence quickly in all cases. Sylvian veins that appeared unclear in the standard microscopic operative field covered with subarachnoid hemorrhage were extremely clearly depicted. These Sylvian ICG findings were helpful in identifying entry points and the dissecting course of the Sylvian fissure. At the time of clipping, no residual fluorescence from Sylvian ICG was present, and aneurysm clipping was not impeded. Sylvian ICG for SAH patients is a novel technique to facilitate dissection of the Sylvian fissure. We believe that this technique will contribute to improved safety of clipping surgery for ruptured aneurysms.

The relationship between noncontrast computed tomography (CT) markers, which predict the expansion of spontaneous intracerebral hemorrhage (sICH) under conservative treatment, and postoperative rebleeding (PR) after treatment by directly removing the sICH is unknown. This study investigated the relationship between noncontrast CT markers and PR in patients with sICH treated by endoscopic surgery.The study population included 92 patients with available data who underwent endoscopic surgery for sICH at our institution from January 2010 to September 2018. The correlations between PR and preoperative noncontrast CT markers, including the blend sign, hypodensities, black hole sign, heterogeneous density, and island signs, were retrospectively evaluated.In 5 of the 18 patients (27.8%) with the blend sign, PR developed, whereas only 5 of 74 patients (6.8%) without the blend sign developed PR. In the univariate regression analyses, manifestation of hydrocephalus (odds ratio [OR], 8.75; 95% confidence interval [CI], 2.15-35.68; P = 0.002), presence of the blend sign (OR, 5.31; 95% CI, 1.34-20.97; P = 0.02), and insertion of external ventricular drainage (OR, 13.88; 95% CI, 3.22-59.77; P0.001) were significant risk factors. The other radiographic markers were not associated with PR. In a multivariate analysis, the presence of the blend sign (OR, 22.07; 95% CI, 2.18-223.60; P = 0.009) was the only independent predictor of PR.The blend sign is likely to be a strong predictor for PR in patients who undergo endoscopic surgery for sICH. To improve the prognosis of patients with sICH, further studies are needed to establish new treatment strategies and surgical procedures.

Prexasertib is a novel inhibitor of checkpoint kinase 1. The primary objective of this study was to evaluate prexasertib tolerability in Japanese patients with advanced solid tumors. This nonrandomized single-arm open-label phase 1 study of prexasertib consisted of 2 dose levels, 80 mg/m2 and the global-recommended dose based on a US study of 105 mg/m2 , administered intravenously once every 14 days (n = 6 for each dose). Transition to the higher dose proceeded if the frequency of dose-limiting toxicity observed in cycle 1 was

Background and Importance. Subependymoma occurs very rarely in the spinal cord. We report another case of spinal subependymoma along with a review of the literature and discussion of a radiological finding that is useful for preoperative diagnosis of this tumor.Clinical Presentation. A 51-year-old man presented with a 2-year history of progressive muscle weakness in the right lower extremity. Sagittal magnetic resonance imaging (MRI) showed spinal cord expansion at the Th7–12 vertebral level. Surgical resection was performed and the tumor was found to involve predominantly subpial growth. Histological diagnosis was subependymoma, classified as Grade I according to criteria of World Health Organization. We made an important discovery of what seems to be a characteristic appearance for spinal subependymoma on sagittal MRI. Swelling of the spinal cord is extremely steep, providing unusually large fusiform dilatation resembling a bamboo leaf. We have termed this characteristic MRI appearance as the “bamboo leaf sign.” This characteristic was apparent in 76.2% of cases of spinal subependymoma for which MRI findings were reported.Conclusion. The bamboo leaf sign on spinal MRI is useful for differentiating between subependymoma and other intramedullary tumors. Neurosurgeons encountering the bamboo leaf sign on spinal MRI should consider the possibility of subependymoma.

Mechanical thrombectomy was demonstrated to be useful for acute ischemic stroke. However, whether it is beneficial for patients with poor prestroke conditions, such as older adults and those with low activity of daily living, is unclear.A total of 134 patients who underwent mechanical thrombectomy in our hospital between April 2015 and January 2019 were retrospectively evaluated. Good outcome was defined as modified Rankin scale score of 0-2 at 90 days after stroke onset. Several factors were analyzed to assess their effects on clinical outcomes.At 90 days after stroke onset, 37.3% (50 of 134) of patients had a good outcome. Prestroke modified Rankin scale score was independently associated with a good outcome (odds ratio .39, 95% confidence interval .22-.67, P.001). In patients with prestroke modified Rankin scale score 0-1, 55.4% (46 of 83) had a good outcome, and no significant difference in prognosis was found between patients aged less than 80 years and those aged greater than or equal to 80 years (P = .64). More than half the patients with prestroke modified Rankin scale score greater than or equal to 2 were graded as modified Rankin scale score 5-6 at 90 days regardless of age, which was significantly higher than those with prestroke modified Rankin scale score 0-1 (P.001).Patients with prestroke modified Rankin scale score 0-1 are expected to have a good prognosis after mechanical thrombectomy even if aged greater than or equal to 80 years. Patients with prestroke modified Rankin scale score greater than or equal to 2 might have an extremely poor prognosis, and we should be more careful in selecting candidates for mechanical thrombectomy.

OBJECTIVEAging of the population may lead to epidemiological changes with respect to chronic subdural hematoma (CSDH). The objectives of this study were to elucidate the current epidemiology and changing trends of CSDH in Japan. The authors analyzed patient information based on reports using a Japanese administrative database associated with the diagnosis procedure combination (DPC) system.METHODSThis study included patients with newly diagnosed CSDH who were treated in hospitals participating in the DPC system. The authors collected data from the administrative database on the following clinical and demographic characteristics: patient age, sex, and level of consciousness on admission; treatment procedure; and outcome at discharge.RESULTSA total of 63,358 patients with newly diagnosed CSDH and treated in 1750 DPC participation hospitals were included in this study. Analysis according to patient age showed that the most common age range for these patients was the 9th decade of life (in their 80s). More than half of patients 70 years old or older presented with some kind of disturbance of consciousness. Functional outcomes at discharge were good in 71.6% (modified Rankin Scale [mRS] score 0–2) of cases and poor in 28.4% (mRS score 3–6). The percentage of poor outcomes tended to be higher in elderly patients. Approximately 40% of patients 90 years old or older could not be discharged to home. The overall recurrence rate for CSDH was 13.1%.CONCLUSIONSThis study shows a chronological change in the age distribution of CSDH among Japanese patients, which may be affecting the prognosis of this condition. In the aging population of contemporary Japan, patients in their 80s were affected more often than patients in other age categories, and approximately 30% of patients with CSDH required some help at discharge. CSDH thus may no longer have as good a prognosis as had been thought.

Background & Aims Esophageal squamous cell carcinoma (ESCC) is the predominant form of esophageal cancer in Japan. Smoking and drinking alcohol are environmental risk factors for ESCC, whereas single nucleotide polymorphisms in ADH1B and ALDH2 , which increase harmful intermediates produced by drinking alcohol, are genetic risk factors. We conducted a large-scale genomic analysis of ESCCs from patients in Japan to determine the mutational landscape of this cancer. Methods We performed whole-exome sequence analysis of tumor and nontumor esophageal tissues collected from 144 patients with ESCC who underwent surgery at 5 hospitals in Japan. We also performed single-nucleotide polymorphism array-based copy number profile and germline genotype analyses of polymorphisms in ADH1B and ALDH2 . Polymorphisms in CYP2A6, which increase harmful effects of smoking, were analyzed. Functions of TET2 mutants were evaluated in KYSE410 and HEK293FT cells. Results A high proportion of mutations in the 144 tumor samples were C to T substitution in CpG dinucleotides (called the CpG signature) and C to G/T substitutions with a flanking 5′ thymine (called the APOBEC signature). Based on mutational signatures, patients were assigned to 3 groups, which associated with environmental (drinking and smoking) and genetic (polymorphisms in ALDH2 and CYP2A6 ) factors. Many tumors contained mutations in genes that regulate the cell cycle ( TP53, CCND1, CDKN2A , FBXW7 ); epigenetic processes ( MLL2, EP300, CREBBP , TET2 ); and the NOTCH ( NOTCH1 , NOTCH3 ), WNT ( FAT1 , YAP1 , AJUBA ) and receptor-tyrosine kinase−phosphoinositide 3-kinase signaling pathways ( PIK3CA , EGFR , ERBB2 ). Mutations in EP300 and TET2 correlated with shorter survival times, and mutations in ZNF750 associated with an increased number of mutations of the APOBEC signature. Expression of mutant forms of TET2 did not increase cellular levels of 5-hydroxymethylcytosine in HEK293FT cells, whereas knockdown of TET2 increased the invasive activity of KYSE410 ESCC cells. Computational analyses associated the mutations in NFE2L2 we identified with transcriptional activation of its target genes. Conclusions We associated environmental and genetic factors with base substitution patterns of somatic mutations and provide a registry of genes and pathways that are disrupted in ESCCs. These findings might be used to design specific treatments for patients with esophageal squamous cancers.