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Aggression is the most common adverse effect of antiepileptic drugs (AEDs). This study aimed to investigate the association of aggression with AED use. The reporting odds ratio (ROR) from adverse event reports, submitted to the Japanese Adverse Drug Event Report database between 2004 and 2020, was used to calculate and investigate the association between AEDs and aggression. We also analyzed the association of aggression with the combined use of AEDs and the relationship between AED-associated aggression and patient characteristics. A total of 433 patients developed aggression. Significant aggression signals were detected for perampanel (crude ROR: 325.04, 95% confidence interval (CI): 118.48-752.58, p 0.01), levetiracetam (crude ROR: 17.14, 95% CI: 10.33-26.90, p 0.01), lacosamide (crude ROR: 16.90, 95% CI: 2.02-62.51, p 0.01), lamotrigine (crude ROR: 15.98, 95% CI: 9.99-24.39, p 0.01), valproate (crude ROR: 6.68, 95% CI: 4.27-10.02, p 0.01), and carbamazepine (crude ROR: 2.47, 95% CI: 1.17-4.59, p 0.01). The combined therapy with perampanel and levetiracetam had a significant aggression signal (adjusted ROR: 25.90, 95% CI: 1.14-59.10, p 0.01). In addition, we found that aggression frequently occurred in patients60 year (adjusted ROR: 2.88, 95% CI: 1.49-5.56, p 0.01) treated with levetiracetam. These results may be useful for minimizing the risk of aggression during the treatment of AEDs.

Poor adherence to medication in patients with heart failure (HF) is associated with poor clinical outcomes. Although social support has been reported to improve medication adherence in patients with HF, the detailed underlying mechanism of this association is unclear. This study investigated appropriate social support types to ensure medication adherence, as well as patient characteristics that benefit from such social support in patients with HF. This was a retrospective observational study investigating the association of social support with medication adherence in 824 patients with HF who were registered in a prospective multicenter database. First, we analyzed the association between social support types and poor medication adherence leading to hospitalization. An interaction analysis was performed to detect patients' characteristics that benefited most from social support in terms of medical adherence. Fifty patients (6.1%) were hospitalized for poor adherence to medications. Multivariable analysis revealed that not receiving assisted living, which was defined as having supporting individuals at least once a week, was independently associated with poor medication adherence-related hospitalization. An interaction analysis revealed that patients with dementia benefited from assisted living significantly, whereas male patients or current smokers did not. Summarily, assisted living at least once a week was appropriate for improving medication adherence in patients with HF and was particularly effective in patients with dementia. Performed in a super-aging region in Japan, this study may also suggest the relevance of social support in preventing HF exacerbation in other developed countries that will experience an aging society in the near future.

Surgical clipping of anterior communicating artery (ACoA) aneurysms remains challenging due to their complex anatomy. Anatomical risk factors for ACoA aneurysm surgery require further elucidation. The aim of this study is to investigate whether proximity of the midline perforating artery, subcallosal artery (SubCA), and associated anomaly of the ACoA complex affect functional outcomes of ACoA aneurysm surgery. A total of 92 patients with both unruptured and ruptured ACoA aneurysms, who underwent surgical clipping, were retrospectively analyzed from a multicenter, observational cohort database. Association of ACoA anatomy with SubCA origin at the aneurysmal neck under microsurgical observation was analyzed in the interhemispheric approach subgroup (n = 56). Then, we evaluated whether anatomical factors associated with SubCA neck origin affected surgical outcomes in the entire cohort (both interhemispheric and pterional approaches, n = 92). In the interhemispheric approach cohort, combination of A1 asymmetry and aneurysmal size ≥ 5.0 mm was stratified to have the highest probability of the SubCA neck origin by a decision tree analysis. Then, among the entire cohort using either interhemispheric or pterional approach, combination of A1 asymmetry and aneurysmal size ≥ 5.0 mm was significantly associated with poor functional outcomes by multivariable logistic regression analysis (OR 6.76; 95% CI 1.19–38.5; p = 0.03) as compared with A1 symmetry group in the acute subarachnoid hemorrhage settings. Combination of A1 asymmetry and larger aneurysmal size was significantly associated with SubCA aneurysmal neck origin and poor functional outcomes in ACoA aneurysm surgery. Interhemispheric approach may be proposed to provide a wider and unobstructed view of SubCA for ACoA aneurysms with this high-risk anatomical variant.

ObjectivesTo examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan.DesignRetrospective study.SettingSix hundred and thirty-one primary care institutions in Japan.ParticipantsForty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database.Primary and secondary outcome measuresAnnual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points).ResultsIn the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality.ConclusionsThe 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.

background Intracranial hypotension due to cerebrospinal fluid (CSF) leak is often associated with secondary chronic subdural hematoma (CSDH). Although epidural blood patch (EBP) treatment for the CSF leak site has been reported to result in spontaneous regression of the CSDH in most cases, it is still debatable whether blocking CSF leak first in the patients with intracranial hematoma is always safe. Case Description A 72-year-old woman presented with orthostatic headache after a head injury and was diagnosed with intracranial hypotension. Computed tomography myelography and radioisotope cisternography failed to reveal the CSF leak point. The overflow leak test, a novel diagnostic method for intracranial hypotension, revealed a leakage at the cervical spine. Bilateral CSDHs were also observed by a computed tomography scan of the head. We performed EBP at the cervical spine and anticipated subsequent regression of the CSDH by normalizing intrathecal pressure. However, the patient became delirious the morning after EBP, and an emergency burr hole trepanation was performed. The patient's consciousness fully recovered, and her orthostatic headache improved as well. Conclusions This case presentation demonstrated that in the case of intracranial hypotension with secondary CSDH, performing EBP and waiting for subsequent spontaneous regression of CSDH are not necessarily safe. Immediate burr hole trepanation should be prepared for the subsequent rapid symptomatic change of the CSDH after EBP.

Patients receiving vinca alkaloids for hematological malignancies frequently experience constipation that is unresponsive to laxatives. Research on treatment of vinca alkaloid-induced constipation is limited. This study aimed to determine whether the chloride channel activator lubiprostone ameliorates vinca alkaloid–induced constipation in patients with hematological malignancies. In this retrospective cohort study, vinca alkaloid–induced constipation (grade ≥ 3 using the Common Terminology Criteria for Adverse Events) was investigated in patients treated for hematological malignancies between July 2014 and June 2019 who had already been prescribed osmotic laxatives and additionally received either a stimulant laxative or lubiprostone. Univariate and multivariate analyses were performed to identify the risk factors for persistent constipation after introduction of the second laxative. A propensity score model was used to match 67 patients taking a stimulant laxative and 67 treated with lubiprostone, and the occurrence of intractable constipation was compared between groups. Overall, 203 patients were included, among whom 50 (25%) had constipation. On multivariate analysis, body mass index, opioid use, and addition of lubiprostone were independently associated with constipation. Patients treated with lubiprostone were significantly less likely to experience intractable constipation than did those treated with stimulant laxatives (10% vs. 34%, P = 0.002). Moreover, post-constipation diarrhea was significantly less frequent among patients treated with lubiprostone (42% vs. 63%, P = 0.024). Lubiprostone was more effective than stimulant laxatives at treating vinca alkaloid–induced intractable constipation in patients with hematological malignancies, and its use could enable safe vinca alkaloid chemotherapy.

OBJECTIVESeveral environmental factors have been reported to correlate with incidence of spontaneous subarachnoid hemorrhage (SAH). However, because of different patient selection and study designs among these studies, meteorological factors that trigger the incidence of SAH in a short hazard period remain unknown. Among meteorological factors, daily temperature changes may disrupt and violate homeostasis and predispose to cerebrovascular circulatory disturbances and strokes. The authors aimed to investigate whether a decline in the temperature from the highest of the previous day to the lowest of the event day (temperature decline from the previous day [TDP]) triggers SAH in the prefecture-wide stroke database.METHODSAll 28 participating institutions with primary or comprehensive stroke centers located throughout Kochi Prefecture, Japan, were included in the study. Data collected between January 2012 and December 2016 were analyzed, and 715 consecutive SAH patients with a defined date of onset were enrolled. Meteorological data in this period were obtained from the Kochi Local Meteorological Observatory. A case-crossover study was performed to investigate association of TDP and other environmental factors with onset of SAH.RESULTSThe increasing TDP in 1°C on the day of the SAH event was associated with an increased incidence of SAH (OR 1.041, 95% CI 1.007–1.077) after adjustment for other environmental factors. According to the stratified analysis, a significant association between TDP and SAH was observed in women, patients < 65 years old, and patients with weekday onset. Among these factors, increasing TDP had a great impact on SAH onset in patients < 65 years old (p = 0.028, Mann-Whitney U-test).CONCLUSIONSTDP, temperature decline from the highest of the previous day to the lowest of the day, was correlated with the incidence of spontaneous SAH, particularly in younger patients < 65 years old.

The early Solar System comprised a broad area of abiotically created organic compounds, including interstellar organics which were integrated into planetesimals and parent bodies of meteorites, and eventually delivered to the early Earth. In this study, we simulated interstellar complex organic compounds synthesized by proton irradiation of a gas mixture of CO, NH3, and H2O, which are known to release amino acids after acid hydrolysis on the basis of Kobayashi et al. (1999) who reported that at the first stage of chemical evolution, the main compounds formed abiotically are complex organic compounds with high molecular weights. We examined their possible hydrothermal alteration and stabilities as amino acid precursors under high temperature and pressure conditions simulating parent bodies of meteorites by using an autoclave. We reported that all samples treated at 200–300 °C predominantly released glycine and alanine, followed by α-aminobutyric acid, and serine. After heating, amino acid concentrations decreased in general; however, the recovery ratios of γ-aminobutyric acid increased with temperature. The interstellar complex organic analog could maintain as amino acid precursors after being treated at high temperature (200–300 °C) and pressure (8–14 MPa). However, the molecular structures were altered during heating to form organic compounds that are more stable and can survive in elevated hydrothermal conditions.

Background Although non-stroke vertebral artery dissection (VAD) is diagnosed using MRI, detecting the subtle intravascular structure remains challenging. This study aimed to evaluate the validity of quantitative intravascular scanning based on novel zoomed high-resolution black blood (Z-HB) MRI for distinguishing VAD from other vessel pathologies. Methods Twenty-one patients with non-stroke VAD and 18 with symptomatic atherosclerotic plaques in their vertebral artery underwent Z-HB MRI and subsequent profile curve processing. Axial Z-HB imaging was obtained from dissected and normal segments in patients with VAD and atherosclerotic plaque in patients with ischemia. We investigated the qualitative categorization of the scanning patterns of the intravascular signals. We also evaluated the quantitative ability of each profile curve to discriminate multiple vessel pathologies by analyzing the receiver operating characteristics curves. Results Profile curve processing of 140 Z-HB images categorized the intravascular signal patterns into luminal, asymmetrical, and omega types. The asymmetrical type included both dissecting and atherosclerotic vessels, and the omega type included dissecting and normal vessels. In the asymmetrical type, quantitative evaluation successfully distinguished intramural hematomas of VAD from atherosclerotic plaque with an area under the curve of 0.80. The intimal flap of the VAD was distinguished from the blood flow artifact of the normal vessel with an area under the curve of 0.93 in the omega type. Conclusions A combination of novel Z-HB MRI and profile curve processing provided an ultra-high-resolution analysis of the intravascular structure of non-stroke VAD and successfully distinguished VAD from normal vessels or atherosclerotic plaques.

Amino acids have been detected in extraterrestrial bodies such as carbonaceous chondrites (CCs), which suggests that extraterrestrial organics could be the source of the first life on Earth, and interplanetary dust particles (IDPs) or micrometeorites (MMs) are promising carriers of extraterrestrial organic carbon. Some amino acids found in CCs are amino acid precursors, but these have not been well characterized. The Tanpopo mission was conducted in Earth orbit from 2015 to 2019, and the stability of glycine (Gly), hydantoin (Hyd), isovaline (Ival), 5-ethyl-5-methylhydantoin (EMHyd), and complex organics formed by proton irradiation from CO, NH

BACKGROUND Use of 5-aminolevulinic acid for photodynamic malignant tumor diagnosis reportedly causes intraoperative hypotension (systolic blood pressure < 70 mmHg) during urologic surgery. However, its association with intraoperative hypotension in malignant glioma surgery and underlying mechanisms has not been elucidated yet. This study aimed to investigate whether 5-aminolevulinic acid administration is associated with intraoperative hypotension in malignant glioma surgery and explore the mechanisms of 5-aminolevulinic acid-induced hypotension in vitro. METHODS In this retrospective multicenter cohort study, we investigated intracellular nitric oxide as a candidate mediator of hypotension in response to 5-aminolevulinic acid in vitro in human umbilical vein endothelial cell cultures. RESULTS Of 142 patients, 94 underwent 5-aminolevulinic acid-guided surgery. Systolic blood pressure was significantly lower throughout surgery with 5-aminolevulinic acid administration. 5-Aminolevulinic acid administration was an independent risk factor for intraoperative hypotension according to multivariable logistic regression analysis (89% vs. 56%; odds ratio=6.72, 95% confidence interval [2.05-22.1], P=0.002). In subgroup analysis of the 5-aminolevulinic acid group, increasing age and use of renin-angiotensin system inhibitors had a synergistic effect with 5-aminolevulinic acid on decreased blood pressure. In the vascular endothelial cell culture study, 5-aminolevulinic acid induced a significant increase in intracellular nitric oxide generation. CONCLUSIONS 5-Aminolevulinic acid administration was associated with intraoperative hypotension in malignant glioma surgery, with increasing age and use of renin-angiotensin system inhibitors boosting the blood pressure-lowering effect of 5-aminolevulinic acid. According to in vitro results, the low blood pressure induced by 5-aminolevulinic acid may be mediated by a nitric oxide increase in vascular endothelial cells.

OBJECTIVEShunt-dependent hydrocephalus (SDHC) may arise after aneurysmal subarachnoid hemorrhage (aSAH) as CSF resorptive mechanisms are disrupted. Using propensity score analysis, the authors aimed to investigate which treatment modality, surgical clipping or endovascular treatment, is superior in reducing rates of SDHC after aSAH.METHODSThe authors’ multicenter SAH database, comprising 3 stroke centers affiliated with Kyoto University, Japan, was used to identify patients treated between January 2009 and July 2016. Univariate and multivariate analyses were performed to characterize risk factors for SDHC after aSAH. A propensity score model was generated for both treatment groups, incorporating relevant patient covariates to detect any superiority for prevention of SDHC after aSAH.RESULTSA total of 566 patients were enrolled in this study. SDHC developed in 127 patients (22%). On multivariate analysis, age older than 53 years, the presence of intraventricular hematoma, and surgical clipping as opposed to endovascular coiling were independently associated with SDHC after aSAH. After propensity score matching, 136 patients treated with surgical clipping and 136 with endovascular treatment were matched. Propensity score–matched cohorts exhibited a significantly lower incidence of SDHC after endovascular treatment than after surgical clipping (16% vs 30%, p = 0.009; OR 2.2, 95% CI 1.2–4.2). SDHC was independently associated with poor neurological outcomes (modified Rankin Scale score 3–6) at discharge (OR 4.3, 95% CI 2.6–7.3; p < 0.001).CONCLUSIONSSDHC after aSAH occurred significantly more frequently in patients who underwent surgical clipping. Strategies for treatment of ruptured aneurysms should be used to mitigate SDHC and minimize poor outcomes.

OBJECTIVEAlthough endovascular therapy is favored for acutely ruptured intracranial aneurysms, hematological factors associated with acute subarachnoid hemorrhage (SAH) may predispose to procedure-related ischemic complications. The aim of this study was to evaluate whether an elevated level of plasma D-dimer, a parameter of hypercoagulation in patients with acute SAH, is correlated with increased incidence of thromboembolic events during endovascular coiling of ruptured aneurysms.METHODSThe authors analyzed data from 103 cases of acutely ruptured aneurysms (in 103 patients) treated with endovascular coil embolization at a single institution. Factors associated with elevated D-dimer level on admission were identified. The authors also evaluated whether D-dimer elevation was independently correlated with increased incidence of perioperative thromboembolic events.RESULTSAn elevated D-dimer concentration (≥ 1.0 μg/ml) on admission was observed in 70 (68.0%) of 103 patients. Increasing age (p < 0.001, Student t-test) and poor initial neurological grade representing World Federation of Neurosurgical Societies (WFNS) grade IV or V (p = 0.0018, chi-square test) were significantly associated with D-dimer elevation. Symptomatic thromboembolic events occurred in 11 cases (10.7%). Elevated D-dimer levels on admission (OR 1.34, 95% CI 1.10–1.62, p = 0.0029) independently carried a higher risk of thromboembolic events after adjustment for potential angiographic confounders, including wide neck of the aneurysm and large aneurysm size.CONCLUSIONSElevated D-dimer levels on admission of patients with acute SAH were significantly associated with increased incidence of thromboembolic events during endovascular coiling of ruptured aneurysms.

Background: Flow diverter (FD) placement is generally effective for intractable internal carotid artery (ICA) aneurysms. However, salvage treatment for the aneurysm enlarging even after FD placement remains to be elucidated. Additional overlapping FD placement is considered the first-line treatment for residual or recurrent aneurysms. However, it is unclear whether overlapping FD is also effective for enlarging giant aneurysms that are considered impending rupture status. Although parent artery occlusion is a promising option, treatment strategy must be optimized, especially when a critical perforating artery is involved. Case Description: A 74-year-old woman experienced rapid symptomatic growth of her giant supraclinoid ICA aneurysm 10 months after FD placement. We assumed that reinforcement of flow diverting effect alone would be less effective for this extremely intractable aneurysm with more aggressive clinical feature so that surgical bailout by parent artery occlusion was planned. Complete ICA obliteration underneath the aneurysm was unavailable due to the presence of anterior choroidal artery. Thus, we took a flow alteration strategy, where we created minimal retrograde flow through the parent artery by a combination of an extracranial-intracranial bypass and targeted endovascular proximal parent artery obliteration, resulting in prevention of aneurysmal rupture and further growth. Conclusion: Impending rupture of the intracranial giant aneurysm after FD placement may be controllable with a tailor-made parent artery occlusion strategy even when a critical perforating artery is involved.

Background: Many randomized controlled trials (RCT) have assessed new treatments in subarachnoid hemorrhage (SAH), yet most show no treatment efficacy. One explanation is the statistical analysis of the primary endpoint was not as efficient as possible. We reanalyzed SAH RCTs with various statistical tests to determine whether the statistical method affects RCT primary outcome.Methods: Individual patient data for the primary outcome (Glasgow outcome scale [GOS]) of two SAH RCTs were analyzed using 15 statistical methods. For tests requiring outcome dichotomization, multiple cut-points in the 5-level GOS were assessed. Next, a synthetic dataset generated using random sampling with replacement from ten SAH RCTs was assessed using the same statistical tests. A Friedman test (two-way non-parametric analysis of variance) determined which tests produced the highest average absolute Z-values. The number of times each test reported significance of pResults: Bootstrapping with replacement produced the best-ranking results, followed by three χ2-tests: one differentiating excellent (GOS=5) from good (GOS=4), poor (GOS=2-3), or dead (GOS=1) outcomes; one differentiating favorable (GOS=4-5) from poor or dead outcomes; and one differentiating favorable (GOS=4-5) from unfavorable outcomes. Each of these reported statistical significance for both RCTs, as did the following ranked tests, respectively: Wilcoxon median test, Student’s t-test, ordinal logistic regression, median test, and a chi-square dichotomizing excellent (GOS≥4) and inferior outcomes. Statistical significance for one or neither RCT was reported by two Cochrane-Armitage tests and two logistic regressions with alternate versions of bucketing, the Kolmogorov-Smirnov test and chi-square test differentiating surviving from dead patients. The synthetic dataset returned similar results, with the same nine most and six least efficient tests.Conclusions: Bootstrapping produced the most efficient results but is time-and resource-intensive. Chi-square tests grouping outcomes into dichotomous or multiple buckets are also efficient, and their ease of use and popularity make them appropriate candidates for statistical analysis in future SAH RCTs.

Background: Tranexamic acid (TA) administration in aneurysmal subarachnoid hemorrhage (SAH) within the first 24 hours may reduce the incidence of early aneurysmal rebleeding. However, this is also the potential for an increased risk of delayed cerebral ischemia if TA is administered for more than 72 hours following the initial aneurysmal rupture. Methods: In the ultra-early tranexamic acid after subarachnoid hemorrhage randomized controlled trial by Post et al., patients were randomized to receive TA within the first 24 hours, or until start of aneurysm treatment. These results were compared to a matched control group. Results: Ultra-early administration (≤24 h) of TA reduced the incidence of rebleeding, and did not alter the incidence of delayed cerebral ischemia and/or extracranial thrombosis. Further, no significant differences were noted between the TA group and control arm in the incidence of good (modified Rankin scores 0-3) clinical outcomes at 6 months. Conclusion: Ultra-early administration of TA (≤24 h) resulted in a lower rate of recurrent hemorrhage, without increasing the incidence of delayed cerebral ischemia in SAH patients.

Introduction: Subarachnoid hemorrhage (SAH) mortality is decreasing, but data on functional outcomes over time is lacking. Methods: We created trends of good (Glasgow Outcomes Scale [GOS] of 4 or 5) and optimal (GOS of 5) functional outcomes and mortality (GOS of 1) using linear regression in 15 SAH trials and registries from 1982 to 2014. Models adjusted for age, sex, history of hypertension, World Federation of Neurological Surgeons grade, Fisher grade, aneurysm size, location, and repair modality, and whether data was from a clinical trial or registry. Analyses were repeated separately for the clinical trials and registries. Missing data were handled with multiple imputation. Results: Overall, 13,343 SAH patients were included. 9,524 (71%) patients had good functional outcome, while 1,608 (12%) died. There was a 0.6% adjusted improvement (95% confidence interval [CI]: 0.5% to 0.7%; p Conclusions: SAH morbidity and mortality decreased from the 1980s to 2010s. This data can be helpful for researchers planning trials, clinicians discussing expected outcomes with patients and family members, and healthcare administrators planning resource utilization.

A hybrid operating room(Hybrid OR), where operative equipment and flat panel angiography are both available, is becoming common for complex cerebrovascular surgery. However, the current Hybrid OR remains suboptimal as it is not cost-effective and contains uncomfortable operating beds, and a single-plane flat panel. Therefore, we introduced a novel Hybrid OR system, which has a biplane flat panel detector and three mutually exchangeable tailor-made operating beds. In this article, we report our preliminary experience of this novel Hybrid OR, focusing on improved cost-effectiveness by the availability of diagnostic angiography and standard endovascular surgery, optimal selection of three different types of operating beds, and procedural workflow in individual hybrid cerebrovascular surgery.

Background Cerebrospinal fluid (CSF) hypovolemia is usually treated via an epidural blood patch (EBP). Accurate placement of the EBP at the site of CSF leakage is required for successful treatment of CSF hypovolemia. The thoracolumbar spine is evidently a common site of leakage, but because rates of detection of the leakage site via conventional imaging have historically not been high, there may be other common leakage sites. In this study, CSF leakage sites were identified via a combination of conventional imaging, a new method called the overflow leak test, and patient interviews. Methods CSF leakage sites were identified using computed tomography myelography, radioisotope cisternography, and the overflow leak test in 14 patients with CSF hypovolemia. The patients were also asked about their history with regard to potential trauma. EBP was performed, and the accuracy of leakage site identification was assessed. Results Conventional imaging identified a leakage site in 7 of 14 patients, and in most cases it was in the lumbar spine. In the remaining 7 cases, the overflow leak test and ascertaining a history of trauma facilitated identification of the cervical spine as a leakage site. The site of the EBP was the cervical spine in 10 patients and the lumbar spine in 4 patients. Complete recovery was observed in 13 of 14 patients. Conclusions The cervical spine was a common leakage site in this study. Leakage in the cervical spine was undetectable via conventional imaging, suggesting that many cases of cervical spine leakage may remain undetected.

Astroblastoma is a rare, supratentorial glial tumor, occurring predominantly in children and young adults. However, treatment strategies have not yet been established for this rare disease.A 6-year-old boy presented with headache and nausea. CT and MRI revealed a left frontal mass lesion with slight edema and macrocalcifications. Gross tumor resection was performed. Histological examination found neoplastic cells with astroblastic characteristics, and a striking perivascular array of pseudorosettes. The final diagnosis was high-grade astroblastoma. MRI 13 months after surgery suggested local recurrence, and an enlargement was found 3 months later. Stereotactic radiotherapy(SRT)was performed. MRI after SRT showed enhanced cyst formation around the tumor bed, suggesting tumor recurrence. However,Astroblastoma is rare, therefore, no optimal management is known. SRT may be effective to treat recurrent astroblastomas.

Background Anatomical variations of the course of the internal carotid artery (ICA) may complicate surgical clipping of posterior communicating artery (PCoA) aneurysms by narrowing the retrocarotid window. We evaluated the efficacy of the periclinoid surgical maneuvers for expanding the retrocarotid window and analyzed computed tomography angiography (CTA) data from patients with PCoA aneurysms to define parameters for low-coursing ICAs. Methods Using cadaveric specimens, standard pterional craniotomies were fashioned and extradural or intradural periclinoid surgical maneuvers—cutting of the meningo-orbital band, anterior clinoidectomy, and cutting of the distal dural ring (DDR)—were performed, and their relative advantages for expanding the retrocarotid window were assessed. Additionally, preoperative CTA data from 24 patients with PCoA aneurysms used to calculate the angles of the ICA relative to the skull base. Results Periclinoid maneuvers, especially the anterior clinoidectomy, provided additional exposure of the retrocarotid space. Cutting of the DDR allowed for partial mobilization of the ICA and widened the retrocarotid surgical window, enhancing maneuverability. The anterior clinoidectomy with cutting of the DDR allowed for enhanced exposure of the medial, middle, and posterolateral aspects of the retrocarotid space. Cutting the anterior petroclinoid fold and mobilizing cranial nerve III provided wide exposure of the lateral aspect of retrocarotid space. Conclusion When clipping PCoA aneurysms in the presence of normal-coursing ICAs (approximately ≥30° ICA angle), a standard pterional craniotomy with anterior clinoidectomy and cutting of the DDR allows for substantial expansion of the retrocarotid window.

Patients receiving vinca alkaloids for hematological malignancies frequently experience constipation that is unresponsive to laxatives. Research on treatment of vinca alkaloid-induced constipation is limited. This study aimed to determine whether the chloride channel activator lubiprostone ameliorates vinca alkaloid-induced constipation in patients with hematological malignancies. In this retrospective cohort study, vinca alkaloid-induced constipation (grade ≥ 3 using the Common Terminology Criteria for Adverse Events) was investigated in patients treated for hematological malignancies between July 2014 and June 2019 who had already been prescribed osmotic laxatives and additionally received either a stimulant laxative or lubiprostone. Univariate and multivariate analyses were performed to identify the risk factors for persistent constipation after introduction of the second laxative. A propensity score model was used to match 67 patients taking a stimulant laxative and 67 treated with lubiprostone, and the occurrence of intractable constipation was compared between groups. Overall, 203 patients were included, among whom 50 (25%) had constipation. On multivariate analysis, body mass index, opioid use, and addition of lubiprostone were independently associated with constipation. Patients treated with lubiprostone were significantly less likely to experience intractable constipation than did those treated with stimulant laxatives (10% vs. 34%, P = 0.002). Moreover, post-constipation diarrhea was significantly less frequent among patients treated with lubiprostone (42% vs. 63%, P = 0.024). Lubiprostone was more effective than stimulant laxatives at treating vinca alkaloid-induced intractable constipation in patients with hematological malignancies, and its use could enable safe vinca alkaloid chemotherapy.

OBJECTIVEDelayed cerebral ischemia (DCI) is an important complication after aneurysmal subarachnoid hemorrhage (aSAH). Although intrathecal milrinone injection via lumbar catheter to prevent DCI has been previously reported to be safe and feasible, its effectiveness remains unknown. The goal of this study was to evaluate whether intrathecal milrinone injection treatment after aSAH significantly reduced the incidence of DCI.METHODSThe prospectively maintained aSAH database was used to identify patients treated between January 2010 and December 2015. The cohort included 274 patients, with group assignment based on treatment with intrathecal milrinone injection or not. A propensity score model was generated for each patient group, incorporating relevant patient variables.RESULTSAfter propensity score matching, 99 patients treated with intrathecal milrinone injection and 99 without treatment were matched on the basis of similarities in their demographic and clinical characteristics. There were significantly fewer DCI events (4% vs 14%, p = 0.024) in patients treated with intrathecal milrinone injection compared with those treated without it. However, there were no significant differences between the 2 groups with respect to their 90-day functional outcomes (46% vs 36%, p = 0.31). The likelihood of chronic secondary hydrocephalus, meningitis, and congestive heart failure as complications of intrathecal milrinone injection therapy was also similar between the groups.CONCLUSIONSIn propensity score–matched groups, the intrathecal administration of milrinone via lumbar catheter showed significant reduction of DCI following aSAH, without an associated increase in complications.

Vertebral arteriovenous fistula (VAVF), which can cause subarachnoid hemorrhage (SAH) when having a perimedurally drainage, has been reported as a rare vascular abnormality in patients with neurofibromatosis type 1 (NF-1). In addition, extracranial vertebral aneurysm (EVAn) coexisting with VAVF and NF-1 is considered rare, and further complication with SAH is extremely rare in patients. There is only one reported case of NF-1 complicated with SAH from VAVF with an EVAn. Here, we present a case of a middle-aged patient with NF-1. The VAVF accompanied by an EVAn was detected with an episode of SAH. The VAVF with an EVAn in our case was accompanied with an epidural varix, lacking of perimedullary drainage, which could be a cause for SAH. We speculate the mechanism of SAH from the VAVF with an EVAn lacking of perimedurally drainage, focusing on hemodynamic stress of the VAVF and the tissue fragility related to NF-1.

Metastasis from extracranial tumor into a pituitary adenoma is a rare case. We report a case of metastasis from gastric cancer to a giant pituitary tumor. A 65-year-old man had been drinking more water and had an increased frequency of urine in 10 years. From that time, the patient was gradually aware of the pain in his left eye. In 20XX the patient had a sudden severe headache and pain of his eyes and visited an ophthalmologist. The patient was referred to our institution with general malaise and nausea, vomiting. A cerebral MRI disclosed Extensive neoplastic lesions from the base of the skull to the nasal cavity. The left eye had esotropia and abduction disorder. Laboratory test demonstrated hyponatremia (Na 126mEq/L) and decreased in plasma osmolality (273mOsm/kg), D-dimer, fibrinogen and CA19-9 were high level. One week after admission, the patient’s symptom was getting worse. The patient underwent FDG PET/CT, which showed FDG avid in the gastric wall and clivus tumor. The lesion was suspected gastric cancer and performed Esophagogastroduodenoscopy. The biopsy-based pathology was showed cubic and round cells with high NC ratio and signet-ring cells containing mucin. And clivus tumor was biopsied at an otolaryngologist because part of the tumor was exposed from the nasal cavity. The biopsy-based pathology was showed a small amount of adenocarcinoma cells which is surrounded by pituitary adenoma. The patient was diagnosed as intrapituitary adenoma metastasis from advanced gastric cancer and has been started radiation therapy. But the level of consciousness dropped sharply, so radiation therapy had become difficult to continue. The patient transferred to palliative care ward and died 3 months after his first visit. In this case, diagnosis and treatment were difficult due to the that the image was a finding a malignant tumor and the rapid progression of symptoms.

Background Perforator infarction is a procedure-related complication of surgical clipping of ruptured anterior communicating artery (ACoA) aneurysms. Patients with perforator infarction may present with specific clinical features. The aim of this study was to elucidate incidence, risk factors, clinical course, and outcomes of perforator infarction following surgical clipping of ruptured ACoA aneurysms. Methods Retrospective analysis was performed of 104 patients from a single-center, observational cohort database who underwent surgical clipping for ruptured ACoA aneurysm. Risk factors of perforator infarction were identified. Correlation of perforator infarction with clinical course during hospitalization was investigated, focusing on dysfunction of hypothalamus and cerebral limbic system. We also evaluated any associations between perforator infarction and poor outcomes. Results Perforator infarction was observed in 24 (23.1%) patients. Use of temporary clip ( P = 0.019, χ 2 test) and intraoperative rupture ( P 2 test) were significantly associated with perforator infarction. Patients with perforator infarction had increased likelihood of hyponatremia (odds ratio 6.41 [95% confidence interval 2.27–18.1], P P = 0.004) in the subacute stage of subarachnoid hemorrhage by multivariate analyses. Perforator infarction was an independent risk factor of poor functional outcomes at 3 months (modified Rankin Scale score 3–6; odds ratio 5.29 [95% confidence interval 1.62–17.2], P = 0.006). Conclusions Perforator infarction following surgical clipping of ruptured ACoA aneurysms caused region-specific complications, including hyponatremia and insufficient oral intake, and was associated with poor functional outcomes.

Background In endovascular embolization of intracranial aneurysms, a tortuous cervical internal carotid artery can limit guiding catheter access to a sufficiently high position. Although intermediate distal access catheters can go beyond the tortuous segment of internal carotid arteries, they may increase the risk of procedure-related complications, require significantly complex technical procedures, and limit the use of adjunctive techniques. Using simple neck extension alone, we successfully improved guiding catheter access in 2 patients. Methods Through a provocative test, we confirmed suitability of manual neck extension in 2 patients with severe posterior curvature of a tortuous internal carotid artery. Intraoperatively, we manually extended the neck and stretched the curvatures. We guided a 6F guiding catheter superiorly and performed coil embolization with an occlusion balloon catheter in 1 case and with the balloon-assisted neck remodeling technique in 1 case. Results Coil embolization was completed without any adverse events in both cases. Conclusions The simple neck extension technique successfully improved accessibility of the guiding catheter. As the need for safe and highly skilled intervention increases, our technique may be useful because it can reduce procedure-related complications and allow balloon-assisted techniques.

OBJECTIVEPlasma D-dimer levels elevate during acute stages of aneurysmal subarachnoid hemorrhage (SAH) and are associated with poor functional outcomes. However, the mechanism in which D-dimer elevation on admission affects functional outcomes remains unknown. The aim of this study is to clarify whether D-dimer levels on admission are correlated with systemic complications after aneurysmal SAH, and to investigate their additive predictive value on conventional risk factors for poor functional outcomes.METHODSA total of 187 patients with aneurysmal SAH were retrospectively analyzed from a single-center, observational cohort database. Correlations of plasma D-dimer levels on admission with patient characteristics, initial presentation, neurological complications, and systemic complications were identified. The authors also evaluated the additive value of D-dimer elevation on admission for poor functional outcomes by comparing predictive models with and without D-dimer.RESULTSD-dimer elevation on admission was associated with increasing age, female sex, and severity of SAH. Patients with higher D-dimer levels had increased likelihood of nosocomial infections (OR 1.22 [95% CI 1.07–1.39], p = 0.004), serum sodium disorders (OR 1.11 [95% CI 1.01–1.23], p = 0.033), and cardiopulmonary complications (OR 1.20 [95% CI 1.04–1.37], p = 0.01) on multivariable analysis. D-dimer elevation was an independent risk factor of poor functional outcome (modified Rankin Scale Score 3–6, OR 1.50 [95% CI 1.15–1.95], p = 0.003). A novel prediction model with D-dimer had significantly better discrimination ability for poor outcomes than conventional models without D-dimer.CONCLUSIONSElevated D-dimer levels on admission were independently correlated with systemic complication, and had an additive value for outcome prediction on conventional risk factors after aneurysmal SAH.

The accelerator-based syringe needle-type proton-induced X-ray source, which was proposed by the authors in 2013 as an alternative for prostate cancer brachytherapy, has an essential issue in that its dose distribution is affected by many factors, such as the structure of the needle and incident proton beam conditions. In this paper, as a method of evaluating dose distribution, we propose a Geant4 simulation to study the effect of the incident proton beam condition on the spectrum and distribution of X-ray emission, using experimentally measured proton beam emittance as input data. The results showed that the effect of beam misalignment was significant and confirmed the effectiveness of this method. It is expected that improving this method will clarify the other factors that affect X-ray distribution, so that finally, we can optimize such factors in designing a special dose distribution for the irradiation of tumors of arbitrary size and shape in the tissue. Copyright © 2017 John Wiley & Sons, Ltd.