[How Can We Manage Skin Incision and Craniotomy for Avoidance of Postoperative Esthetic Concern?]

A successful microsurgical neck clipping of cerebral aneurysm is one of the milestones for neurosurgeons. However, a 'complete clip closure of aneurysm without neurological deficit' is not enough for the patient, as esthetic problems can occur several months after the surgery. In this paper, we describe a series of surgical tips concerning the surgical steps starting from skin incision to craniotomy to minimize the esthetic impact. First, the skin incision should be oriented perpendicular to the fall pattern of hair follicles in the temporal area so that the hair covers the scar line and the scalpel is tilted about 50° to face in the frontal area for preservation of hair roots. After minimum coagulation and skin clip application, interfascial fat pad is dissected at 2 cm dorsal to McCarty keyhole to root of zygomatic process, in order to protect facial nerve. Subgaleal connective tissue with periosteum is harvested as a flap for reconstruction of the calvarial defect. The temporal muscle should be dissected from the caudal to rostral position to avoid delayed muscular atrophy. Central dural tenting sutures are placed at the dural incision. The craniotomy line should be filled with bone crust and covered by subgaleal connective tissue with the periosteum. Single, short-distance galeal sutures, and loose skin sutures can reduce post-operative granulation. From the day after surgery, the patient can shampoo his/her head.

Neuro-regeneration therapy using human Muse cells is highly effective in a mouse intracerebral hemorrhage model.

A novel type of non-tumorigenic pluripotent stem cell, the Muse cell (multi-lineage, differentiating stress enduring cell), resides in the connective tissue and in cultured mesenchymal stem cells (MSCs) and is reported to differentiate into multiple cell types according to the microenvironment to repair tissue damage. We examined the efficiency of Muse cells in a mouse intracerebral hemorrhage (ICH) model. Seventy µl of cardiac blood was stereotactically injected into the left putamen of immunodeficient mice. Five days later, 2 × 105 of human bone marrow MSC-derived Muse cells (n = 6) or cells other than Muse cells in MSCs (non-Muse, n = 6) or the same volume of PBS (n = 11) was injected into the ICH cavity. Water maze and motor function tests were implemented for 68 days, and immunohistochemistry for NeuN, MAP2 and GFAP was done. The Muse group showed impressive recovery: Recovery was seen in the water maze after day 19, and motor functions after 5 days was compared with the other two groups, with a significant statistical difference (p < 0.05). The survival rate of the engrafted cells in the Muse group was significantly higher than in the non-Muse group (p < 0.05) at day 69, and those cells showed positivity for NeuN (~57%) and MAP-2 (~41.6%). Muse cells could remain in the ICH brain, differentiate into neural-lineage cells and restore functions without inducing them into neuronal cells by gene introduction and cytokine treatment prior to transplantation. A simple collection of Muse cells and their supply to the brain in naïve state facilitates regenerative therapy in ICH.

Effect of Cilostazol on Cerebral Vasospasm and Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Several clinical studies have indicated the efficacy of cilostazol, a selective inhibitor of phosphodiesterase 3, in preventing cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). They were not double-blinded trial resulting in disunited results on assessment of end points among the studies. The randomized, double-blind, placebo-controlled study was performed to assess the effectiveness of cilostazol on cerebral vasospasm. METHODS: Patients with aneurysmal SAH admitted within 24 h after the ictus who met the following criteria were enrolled in this study: SAH on CT scan was diffuse thick, diffuse thin, or local thick, Hunt and Hess score was less than 4, administration of cilostazol or placebo could be started within 48 h of SAH. Patients were randomly allocated to placebo or cilostazol after repair of a ruptured saccular aneurysm by aneurysmal neck clipping or endovascular coiling, and the administration of cilostazol or placebo was continued up to 14 days after initiation of treatment. The primary end point was the occurrence of symptomatic vasospasm (sVS), and secondary end points were angiographic vasospasm (aVS) evaluated on digital subtraction angiography, vasospasm-related new cerebral infarction evaluated on CT scan or MRI, and clinical outcome at 3 months of SAH as assessed by Glasgow Outcome Scale, in which poor outcome was defined as severe disability, vegetative state, and death. All end points were evaluated with blinded assessment. RESULTS: One hundred forty eight patients were randomly allocated to the cilostazol group (n = 74) or the control group (n = 74). The occurrence of sVS was significantly lower in the cilostazol group than in the control group (10.8 vs. 24.3%, p = 0.031), and multiple logistic analysis showed that cilostazol use was an independent factor reducing sVS (OR 0.293, 95% CI 0.099-0.568, p = 0.027). The incidence of aVS and vasospasm-related cerebral infarction were not significantly different between the groups. Poor outcome was significantly lower in the cilostazol group than in the control group (5.4 vs. 17.6%, p = 0.011), and multiple logistic analyses demonstrated that cilostazol use was an independent factor that reduced the incidence of poor outcome (OR 0.221, 95% CI 0.054-0.903, p = 0.035). Severe adverse events due to cilostazol administration did not occur during the study period. CONCLUSIONS: Cilostazol administration is effective in preventing sVS and improving outcomes without severe adverse events. A larger-scale study including more cases was necessary to confirm this efficacy of cilostazol.

[Epidemiological Investigation of Patients in Persistent Vegetative States in Aomori, Japan].

The actual number and condition of Japanese patients in persistent vegetative states have not yet been fully understood. The aim of this study is to investigate the epidemiology of patients in persistent vegetative states in the Aomori prefecture. We sent questionnaires regarding gender, age, cause of persistent vegetative state, and residence of patient to all medical institutions in the Aomori prefecture (n=682). Two hundreds and seventeen institutions (31.8%) replied to the questionnaire, and eleven hundred ninety-eight patients(Male/Female=381/817) were included. Patients over 80 years-old were the most common (63.4%), and cerebrovascular stroke was the major cause (64.4%) of persistent vegetative state. Nursing homes (48.1%) and hospitals (34.6%) were the main care institutions. Population based analysis revealed that 869 persistent vegetative state patients per million were cared for in the Aomori prefecture. This result was twice as many as was previously reported in Miyagi prefecture. The number of patients in persistent vegetative states will increase in the future, due to an increasing elderly population and a high incidence of stroke in this demographic. We therefore predict that increased medical and administrative support will be required in the future.

Factors Affecting Outcomes of Poor-Grade Subarachnoid Hemorrhage.

OBJECTIVE: Poor-grade subarachnoid hemorrhage (SAH) accounts for 20% of all SAH and is associated with poor outcomes. The first step in improving outcomes is to analyze the factors that contribute to poor outcomes. METHODS: This was a multicenter, retrospective, observational, cohort study. Data fields included demographic, clinical, radiological, and outcome data for all spontaneous patients with SAH treated at 4 hospitals in Aomori Prefecture in Japan. Patients with modified Rankin Scale score 0-2 at discharge were defined as the good outcome group, and those with modified Rankin Scale score 3-6 were defined as the poor outcome group, and comparisons were made between the 2 groups. RESULTS: There were 329 eligible patients with poor-grade SAH, 41 with good outcome group, and 288 with poor outcome group. On multivariate analysis of the outcome, conservative treatment (P < 0.001), Fisher group 4 (P < 0.007), age ≥65 years (P = 0.011), and Hunt and Kosnik grade V on admission (P = 0.021) were significant factors contributing to a poor outcome. CONCLUSIONS: Nonelderly patients who are not in grade V and Fisher group 4 should undergo aneurysm treatment as soon as possible because they are more likely to have a good outcome, whereas elderly patients in grade V and Fisher group 4 are unlikely to benefit from aneurysm treatment at present. The development of a treatment for early brain injury may be important to improve the outcomes of patients with poor-grade SAH.

Long-term postoperative prognosis and associated risk factors of chronic subdural hematoma in the elderly.

Surgical treatment for chronic subdural hematoma（CSDH）has contributed to good outcome. However, several recent studies have revealed that surgical outcomes for elderly patients were not decisively good. In this study, prognosis of CSDH patients in elderly were analyzed. This study included 232 CSDH patients who were treated in our department and 2 affiliated hospitals, and poor prognosis was defined as aggravation of modified Rankin scale (mRS) at examination comparing with that at discharge, or mRS 3 and higher at examination. We collected data from medical records and questionnaires on the following clinical characteristics of patients: age, sex, findings at admission, medication of antiplatelets and anticoagulants, radiological findings on computed tomography, recurrence, place of discharge, perioperative systemic complications, and mRS at discharge and at examination. The cut-off value of age for poor prognosis of all CSDH patients was 74 years old in this study. In multivariate analysis of all cases, age was prognostic factor for poor outcome:75 years old or higher（p=0.0002）. In this group, mRS at discharge(p=0.0184) and postoperative medical diseases(p<0.0001) were the risk factors of poor prognosis. In this present study, high age and activities of daily life（ADL） at discharge were significant prognostic factors for poor outcome of CSDH. Improvement of ADL at discharge with care for postoperative systemic complications and careful rehabilitation can contribute to good prognosis for CSDH in elderly patients.

Long-term tumor-free survival case of congenital embryonal tumor with various pathological components.

PURPOSE: Treatment strategy of malignant congenital brain tumor is controversial. We report a congenital embryonal tumor case with various pathological components. METHODS: A normally delivered male infant had an enlarged head circumference at 1 month after birth. The abnormality of the right side of the head was also noted during the routine 4-month health check. The head circumference was 45.1 cm (+2.25, SD); neurological status, however, was normal, with a pediatric GCS of 9 and body weight of 6,370 g (-0.85, SD). Magnetic resonance imaging (MRI) revealed right brain tumor whose size was 99 × 91 × 86 mm. The tumor was enhanced homogeneously with central necrosis, and the margin of the tumor was well circumscribed. RESULTS: We performed a subtotal removal of the tumor. The pathological diagnosis was meningioma (MIB-1 index was 2 %). The residual tumor gradually shrank, and we performed monthly MRI follow-up. The tumor abruptly recurred 7 months after the operation. The level of patient consciousness deteriorated, and emergency removal surgery was performed. The histological examination showed various types of embryonal components without meningioma-like parts. The pathological diagnosis was an embryonal tumor. The MIB-1 index was 48 %. One month after the second operation, dissemination of the tumor occurred at the right temporal lobe, cerebellum, and in subcutaneous tissue. Chemotherapy (vincristine, cisplatin, cyclophosphamide, and etoposide) was initiated following radiation therapy (3 Gy/day, 8×). Adjuvant therapies were effective, and no tumor recurrence was detected during 34 months follow-up. CONCLUSION: Treatment strategies for malignant indefinite diagnosed tumor need to be discussed.

[Chronic subdural hematoma (CSH) complicated by bilateral occipital lobe infarction: two case reports].

Chronic subdural hematoma (CSH) is a common disease that is treated with burr hole drainage by neurosurgeons. The outcome of CSH is mostly favorable. We treated 2 cases with bilateral occipital lobe infarction due to CSH. A 57-year-old woman was ambulatory when she visited a clinic for evaluation of headache. One hour after the CT was taken, she developed acute impairment of consciousness, so that she was referred to our hospital. The second patient was a 73-year-old woman with a history of depression who was involved in a traffic accident 5 weeks before admission to our hospital. She was at first admitted to a psychiatric hospital for evaluation of gait disturbance. Three weeks after she was admitted to the psychiatric hospital, she fell into a coma. She was referred to our hospital. Their brain CT on admission revealed compressed ambient and interpeduncular cistern and bilateral CSH. Although burr hole drainage surgery was performed, the 2 patients developed severe sequelae due to occipital lobe infarction caused by central transtentorial herniation.

Analysis of Factors Influencing Delayed Presentation in Japanese Patients with Subarachnoid Hemorrhage.

OBJECTIVE: Some aneurysmal subarachnoid hemorrhage (SAH) patients are delayed in their presentation. This can cause a washout of the subarachnoid hematoma and a potential misdiagnosis. As a result, they may suffer rerupture of the aneurysm and preventable deterioration. We investigated the factors that influence delayed SAH presentation. METHODS: Aneurysmal SAH patients treated at 9 stroke centers from 2002 to 2020 were included. Age, gender, pre-SAH modified Rankin scale, World Federation of Neurological Surgeons grade, Fisher group, day of presentation, aneurysm treatment method, past history of cerebral stroke, comorbidity of hypertension and/or diabetes mellitus, and modified Rankin scaleat discharge were assessed retrospectively. We formed 2 groups based on the day of presentation after the onset of SAH: day 0-3 (early) and other (delayed). Logistic regression analyses detected the factors that influenced the day of presentation and outcome for SAH. A P- value <0.05 was considered significant. RESULTS: Delayed presentation comprised 282 cases (6.3%) of 4507 included cases. Logistic regression analyses showed that patients in an urban area, of male gender, low WFNS grade and low Fisher group correlated significantly with a delayed presentation. But delayed presentation did not influence outcome at discharge. CONCLUSIONS: Area of residency and gender correlated with delayed presentation after SAH in Japan. Urbanization, male gender, and mild SAH lead patients to delay presentation. The factors underlying these tendencies will be analyzed in a future prospective study.

Verification of a Three-day Hospitalization Protocol for Chronic Subdural Hematoma Surgery.

Chronic subdural hematoma (CSH) is predominantly a disease of the elderly. Aging societies in advanced countries are seeing the number of CSH cases increasing. We applied a three-day hospitalization protocol for CSH surgery to reduce healthcare costs and more efficiently manage hospital beds. We investigated the clinical factors that influenced prolonged hospitalization. From January 2015 to December 2020, we performed irrigation, evacuation, and drainage of CSH cases in 221 consecutive patients. The χ2 test and logistic regression analysis were conducted to detect clinical factors influencing prolonged hospitalization. A p-value below 0.05 was considered statistically significant. Applying a three-day hospitalization protocol showed no adverse outcomes. Fifty-two (24%) of 221 patients experienced prolonged hospitalization. The χ2 test showed that female gender, atrial fibrillation, alcohol abuse, preoperative consciousness level, verbal function disturbance, and perioperative activities of daily living were significantly related to prolonged hospitalization. Female gender, atrial fibrillation, and alcohol abuse were significant factors in the logistic regression analysis. A three-day hospitalization protocol for CSH is suitable for patient care; however, particular attention needs to be focused on the female gender, atrial fibrillation, and alcohol abuse, all three of which prolong hospitalization.

Superiority of Endovascular Coiling Over Surgical Clipping for Clinical Outcomes at Discharge in Patients With Poor-Grade Subarachnoid Hemorrhage: A Registry Study in Japan.

BACKGROUND AND OBJECTIVES: The differences in clinical outcomes between endovascular coiling (EC) and surgical clipping (SC) in patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) are controversial. Therefore, this study aimed to evaluate whether EC is superior to SC and identify risk factors in patients with poor-grade aSAH. METHODS: We used data from the "Predict for Outcome Study of aneurysmal SubArachnoid Hemorrhage." World Federation of Neurological Societies (WFNS) grade III-V aSAH was defined as poor-grade aSAH, and unfavorable clinical outcomes (modified Rankin Scale scores 3-6) were compared between SC and EC after propensity score matching (PSM). In-hospital mortality was similarly evaluated. Predictors of unfavorable clinical outcomes were identified using multivariable analysis. RESULTS: Ultimately, 1326 (SC: 847, EC: 479) and 632 (SC: 316, EC: 316) patients with poor-grade aSAH were included before and after PSM, respectively. Unfavorable clinical outcomes at discharge were significantly different between SC and EC before (72.0% vs 66.2%, P = .026) and after PSM (70.6% vs 63.3%, P = .025). In-hospital mortality was significantly different between groups before PSM (10.5% vs 16.1%, P = .003) but not after PSM (10.4% vs 12.7%, P = .384). Predictors of unfavorable clinical outcomes in both SC and EC were WFNS grade V, older than 70 years, and Fisher computed tomography (CT) grade 4. Predictors of unfavorable clinical outcomes only in SC were WFNS grade IV (odds ratio: 2.46, 95% CI: 1.22-4.97, P = .012) and Fisher CT grade 3 (4.90, 1.42-16.9, P = .012). Predictors of unfavorable clinical outcome only in EC were ages of 50s (3.35, 1.37-8.20, P = .008) and 60s (3.28, 1.43-7.52, P = .005). CONCLUSION: EC resulted in significantly more favorable clinical outcomes than SC in patients with poor-grade aSAH, without clear differences in in-hospital mortality. The benefit of EC over SC might be particularly remarkable in patients with WFNS grade IV and Fisher CT grade 3.

[Questionnaire about care for patients with disturbed consciousness in the Great East Japan Earthquake].

All people in Japan have been affected significantly by the great earthquake in east Japan. We surveyed the care for patients with disturbed consciousness during the disaster, and report the results and lessons learned to prepare for the future. We sent questionnaires about the management strategy for the patients to 17 centers that had reported at the Japan Coma Society meeting in July 2011. Fifteen centers (88%) replied to the questionnaire. Collective results include the following: (1)Disaster strategy manuals exist in 87% of the institutions. (2)Forty-six percent of the manuals have been made during the last 5 years. (3)Manuals, which had been helpful during previous disasters, were effectively used in training for behavioral assessment. (4)Doctors, nurses and facilities management participated in the creation of the manual. (5)There was no tendency for stocking consumable goods. (6)A system for providing needed electricity and fuel during a disaster situation was consistently present. (7)Self-generating electrical power could be continuously provided within 24 hours in 29% of institutions. (8)Provision of batteries to home-care patients was available only in 13% of the institutions. Many institutions had disaster strategy manuals that had been created before the earthquake and these were effectively utilized. Stock control and self-generating emergency power need to be planned for future disaster response. Disaster response for those needing home care is difficult to provide over a long period.

Role of microcirculatory impairment in delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage.

Early brain injury (EBI) is considered an important cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). As a factor in EBI, microcirculatory dysfunction has become a focus of interest, but whether microcirculatory dysfunction is more important than angiographic vasospasm (aVS) remains unclear. Using data from 128 cases, we measured the time to peak (TTP) in several regions of interest on digital subtraction angiography. The intracerebral circulation time (iCCT) was obtained between the TTP in the ultra-early phase (the baseline iCCT) and in the subacute phase and/or at delayed cerebral ischemia (DCI) onset (the follow-up iCCT). In addition, the difference in the iCCT was calculated by subtracting the baseline iCCT from the follow-up iCCT. Univariate analysis showed that DCI was significantly increased in those patients with a prolonged baseline iCCT, prolonged follow-up iCCT, increased differences in the iCCT, and with severe aVS. Poor outcome was significantly increased in patients with prolonged follow-up iCCT and increased differences in the iCCT. Multivariate analysis revealed that increased differences in the iCCT were a significant risk factor that increased DCI and poor outcome. The results suggest that the increasing microcirculatory dysfunction over time, not aVS, causes DCI and poor outcome after aneurysmal aSAH.

Dysembryoplastic Neuroepithelial Tumor of the Infratentorial Multiple Lesions: A Case Report and Review of the Literature.

A dysembryoplastic neuroepithelial tumor (DNT) is a benign neoplasm that usually occurs in the supratentorial cerebral cortex. Here, we report a rare case of an infratentorial DNT in a 42-year-old woman who presented with dizziness and a gait disturbance. Magnetic resonance imaging of the lesion demonstrated hyperintensity on T2-weighted images and hypointensity on T1-weighted images of the left cerebellar hemisphere with a multifocal lesion. Macroscopically, the lesion appeared soft, avascular, and slightly torose at the cortical surface. Histologically, dysplastic disorganization of the cortex and floating neurons were observed. The pathological and immunochemical features of this case agree with the diagnosis of a DNT. The lesion partially included cortical heterotopia, which is a novel observation in an infratentorial DNT. On the basis of the previous reports, we discussed the surgical resection of the infratentorial DNT.

Multiple Spontaneous Arteriovenous Fistulas of the Superficial Temporal Artery.

Objective: Multiple spontaneous arteriovenous fistulas (AVFs) of the external carotid artery (ECA) are rare. We present a case of multiple spontaneous AVFs treated by coil embolization using a combination of the transarterial and transvenous approach. Case Presentation: A 59-year-old woman complained of right pulsatile tinnitus and a mass lesion at the ventral region of the right ear. 3D CTA and cerebral angiography revealed two AVFs on the superficial temporal artery (STA) with an aneurysm 9.8 mm in diameter. A balloon guiding catheter was navigated to the right STA via the right femoral artery. Another balloon guiding catheter was navigated to the right external jugular vein. The STA distal to the aneurysm was embolized with platinum coils by a transvenous approach. The STA proximal to the aneurysm was embolized transarterially and draining veins were embolized transvenously. Her symptoms were cured after endovascular embolization. MRA at 1 day and 6 months postoperatively showed no recurrence of AVFs or aneurysm. Conclusion: Coil embolization of multiple spontaneous AVFs of the ECA using a combined transarterial and transvenous approach is a curable treatment option. Transvenous embolization of an STA distal to an aneurysm is useful.

Chronic Subdural Hematoma, Caused by Disseminated Intravascular Coagulation and/or Anticoagulation Therapy, after COVID-19.

Chronic subdural hematoma (CSDH) typically develops in the supratentorial region in elderly patients. We treated a case of unilateral supratentorial and bilateral infratentorial CSDH, whereby the patient had a coronavirus disease 2019 (COVID-19) infection combined with disseminated intravascular coagulation 2 months earlier. The patient had not experienced any head trauma before the onset of the CSDH. The postoperative course was uneventful, and the patient experienced no neurological deficit. We propose that we should be aware not only of acute ischemic or hemorrhagic diseases after COVID-19 infection but also of chronic subdural hematoma caused by coagulopathy after a COVID-19 infection.

Recent Declining Trend of Incidence Rate of Subarachnoid Hemorrhage in Shimane, Japan: The Japan Incidence of Subarachnoid Hemorrhage (JIS) Study.

The "Izumo Study" revealed the incidence rate of subarachnoid hemorrhage (SAH) in Izumo City, Shimane Prefecture, Japan, from 1980 to 1998. However, no study has been published regarding the incidence of SAH in Shimane Prefecture after 1998. Most studies reporting the incidence of SAH in Japan have been conducted before 2000, although a few have been reported after 2000. This study aimed to assess the estimated age-adjusted incidence rate (AAIR) of SAH in Shimane Prefecture after 1998, following the Izumo Study. A retrospective study was conducted to identify the estimated AAIR of SAH in Shimane Prefecture, using the age-adjusted SAH mortality rate for this population from 1999 to 2017 and assuming that the case-fatality rate of SAH decreased by 0.7% annually from 45% in 1999 to 32.4% in 2017. We used linear regression analysis for trend to the estimated AAIR of SAH. Sensitivity analyses were also conducted by various case-fatality rates of SAH using assuming case-fatality rate based on previous reports. The estimated AAIR of SAH in Shimane Prefecture declined from 33.6 (95% confidence interval [CI]: 29.7-37.9) per 100,000 person-years in 1999, by 26.5%, to 24.7 (95% CI: 21.4-28.5) in 2017 (p < 0.01, r = 0.58). Declining trend of incidence rate of SAH in Shimane Prefecture from 1999 to 2017 was confirmed in this study.

Safety, Pharmacokinetics and Pharmacodynamics of DS-1040, in Combination with Thrombectomy, in Japanese Patients with Acute Ischemic Stroke.

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

Reperfusion Therapy Brings Apixaban Administration Forward in Patients with Nonvalvular Arterial Fibrillation with Anterior Circulation Large Vessel Occlusion or Stenosis.

OBJECTIVE: The initiation of anticoagulant administration after large vessel occlusion (LVO) or stenosis with nonvalvular arterial fibrillation (NAVF) is controversial. We evaluate the timing of anticoagulation and its relationship with clinical factors. METHODS: We enrolled 595 anterior circulation LVO or stenosis with NAVF cases from 38 stroke centers. Laboratory data; activities of daily living; the Alberta Stroke Program Early CT Score (ASPECTS); the National Institutes of Health Stroke Scale (NIHSS) score; occluded artery; treatment methods; date of the initiation of apixaban administration and outcome were recorded. Multivariate analyses were performed after univariate analysis. RESULTS: The median start of apixaban administration after the stroke was 2 days (interquartile range, 1-5; range, 0-14). Multivariate analysis of variance showed that non-internal carotid artery occlusion (F value 4.60), reperfusion therapy (31.1), high ASPECTS (6.27) before anticoagulant intake, and absence of intracranial hemorrhage (12.9) were significantly correlated with early apixaban administration. Multiple logistic regression analysis for independent living at 90 days after the stroke showed significant factors: aging (odds, 0.94; 95% confidence interval [CI], 0.91-0.97); male (odds, 0.46; 95% CI, 0.26-0.79); prestroke independence (odds, 20.7; 95% CI, 6.48-93.9); number of white blood cells (odds, 0.99; 95% CI, 0.97-1.00); non-internal carotid artery occlusion; NIHSS score at 72 hours after the stroke (odds 0.92; 95% CI, 0.89-0.96); ASPECTS before apixaban intake (odds, 1.15; 95% CI, 1.00-1.31) and initiation of apixaban (odds, 0.91; 95% CI, 0.83-0.99). CONCLUSIONS: Early administration of apixaban is induced by nonsevere infarction, reperfusion therapy or none of intracranial hemorrhage and it correlates with an independent long-term outcome.

Usefulness of thallium-201 SPECT in the evaluation of tumor natures in intracranial meningiomas.

INTRODUCTION: Although intracranial meningiomas are regarded as benign tumors, some of them behave clinically as malignant tumors. Past reports suggest that MIB 1 and vascular endothelial growth factor (VEGF) in postoperative tumor specimens correlate with the aggressive nature of tumors, but preoperative prediction of such a nature is more useful for therapeutic planning for the tumor. The purpose of this study was to assess the usefulness of preoperative thallium-201 chloride single-photon emission computed tomography (Tl SPECT) to evaluate biological behavior in intracranial meningiomas. METHODS: Tl SPECT was performed on 39 patients with intracranial meningioma and Tl uptake indices were calculated. The difference in the Tl uptake index between atypical meningiomas and other pathological types of meningioma was evaluated. Moreover, correlation of Tl uptake indices with the MIB1 labeling index was estimated. Tl uptake indices were also compared between VEGF strongly positive and weakly positive meningiomas. RESULTS: The delayed index of atypical meningioma was significantly higher than that of the other pathological types (p = 0.036). Significant correlation was found between the Tl uptake index in the delayed image and MIB1 labeling index (p < 0.0001, R (2) = 0.36). Moreover, VEGF strongly positive meningiomas exhibited a significantly higher Tl uptake index compared to VEGF weakly positive meningiomas in both the early image and the delayed image (p = 0.029, 0.023, respectively). CONCLUSIONS: Tl uptake index may be a possible preoperative surrogate marker of MIB1 and VEGF that is useful in detecting aggressive natures in intracranial meningiomas.