Allogeneic Stem Cell Therapy for Acute Ischemic Stroke: The Phase 2/3 TREASURE Randomized Clinical Trial.

Importance: Cell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow-derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke. Objective: To assess the efficacy and safety of MultiStem when administered within 18 to 36 hours of ischemic stroke onset. Design, Setting, and Participants: The Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized clinical trial was conducted at 44 academic and clinical centers in Japan between November 15, 2017, and March 29, 2022. Inclusion criteria were age 20 years or older, presence of acute ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 8-20 at baseline), confirmed acute infarction involving the cerebral cortex and measuring more than 2 cm on the major axis (determined with diffusion-weighted magnetic resonance imaging), and a modified Rankin Scale (mRS) score of 0 or 1 before stroke onset. Data analysis was performed between May 9 and August 15, 2022. Exposure: Patients were randomly assigned to either intravenous MultiStem in 1 single unit of 1.2 billion cells or intravenous placebo within 18 to 36 hours of ischemic stroke onset. Main Outcomes and Measures: The primary end points were safety and excellent outcome at day 90, measured as a composite of a modified Rankin Scale (mRS) score of 1 or less, a NIHSS score of 1 or less, and a Barthel index score of 95 or greater. The secondary end points were excellent outcome at day 365, mRS score distribution at days 90 and 365, and mRS score of 0 to 1 and 0 to 2 at day 90. Statistical analysis of efficacy was performed using the Cochran-Mantel-Haenszel test. Results: This study included 206 patients (104 received MultiStem and 102 received placebo). Their mean age was 76.5 (range, 35-95) years, and more than half of patients were men (112 [54.4%]). There were no between-group differences in primary and secondary end points. The proportion of excellent outcomes at day 90 did not differ significantly between the MultiStem and placebo groups (12 [11.5%] vs 10 [9.8%], P = .90; adjusted risk difference, 0.5% [95% CI, -7.3% to 8.3%]). The frequency of adverse events was similar between treatment groups. Conclusions and Relevance: In this randomized clinical trial, intravenous administration of allogeneic cell therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve short-term outcomes. Further research is needed to determine whether MultiStem therapy for ischemic stroke has a beneficial effect in patients who meet specific criteria, as indicated by the exploratory analyses in this study. Trial Registration: ClinicalTrials.gov Identifier: NCT02961504.

Power suppression in EEG after the onset of SAH is a significant marker of early brain injury in rat models.

We analyzed the correlation between the duration of electroencephalogram (EEG) recovery and histological outcome in rats in the acute stage of subarachnoid hemorrhage (SAH) to find a new predictor of the subsequent outcome. SAH was induced in eight rats by cisternal blood injection, and the duration of cortical depolarization was measured. EEG power spectrums were given by time frequency analysis, and histology was evaluated. The appropriate frequency band and recovery percentage of EEG (defined as EEG recovery time) to predict the neuronal damage were determined from 25 patterns (5 bands × 5 recovery rates) of receiver operating characteristic (ROC) curves. Probit regression curves were depicted to evaluate the relationships between neuronal injury and duration of depolarization and EEG recovery. The optimal values of the EEG band and the EEG recovery time to predict neuronal damage were 10-15 Hz and 40%, respectively (area under the curve [AUC]: 0.97). There was a close relationship between the percentage of damaged neurons and the duration of depolarization or EEG recovery time. These results suggest that EEG recovery time, under the above frequency band and recovery rate, may be a novel marker to predict the outcome after SAH.

18F-FDG PET/CT Imaging of G-CSF-Producing Inflammatory Myofibroblastic Tumor of the Pleura.

ABSTRACT: We report a case of granulocyte colony-stimulating factor (G-CSF)-producing inflammatory myofibroblastic tumor of the pleura in a 71-year-old man. Contrast-enhanced CT demonstrated multiple pleural masses with pulmonary hilar lymph nodes swelling. 18F-FDG PET/CT demonstrated marked focal FDG uptake in the thoracic masses with diffuse uptake in the bone marrow. Based on the pathological findings and elevated serum G-CSF level, the patient was diagnosed as G-CSF-producing inflammatory myofibroblastic tumor. Because G-CSF-producing tumors demonstrate aggressive clinical course, early and accurate diagnosis is important.

18F-FDG PET/CT Findings of G-CSF-Producing Gallbladder Cancer.

ABSTRACT: We report a case of granulocyte colony-stimulating factor (G-CSF)-producing gallbladder cancer in a 64-year-old man. Contrast-enhanced CT showed an exophytic hypoattenuation mass with peripheral enhancement in the gallbladder. 18F-FDG PET/CT showed avid FDG uptake in the gallbladder mass and diffuse FDG uptake in the bone marrow. The patient was diagnosed with G-CSF-producing gallbladder cancer based on an elevated serum level of G-CSF and histological findings. G-CSF-producing tumors are associated with a poor prognosis because of rapid progression. Early and accurate diagnosis of G-CSF-producing tumors based on characteristic PET/CT findings is important to determine treatment strategies and improve prognosis of patients.

Incidence and clinical characteristics of spinal arteriovenous shunts: hospital-based surveillance in Okayama, Japan.

OBJECTIVE: There have been no accurate surveillance data regarding the incidence rate of spinal arteriovenous shunts (SAVSs). Here, the authors investigate the epidemiology and clinical characteristics of SAVSs. METHODS: The authors conducted multicenter hospital-based surveillance as an inventory survey at 8 core hospitals in Okayama Prefecture between April 1, 2009, and March 31, 2019. Consecutive patients who lived in Okayama and were diagnosed with SAVSs on angiographic studies were enrolled. The clinical characteristics and the incidence rates of each form of SAVS and the differences between SAVSs at different spinal levels were analyzed. RESULTS: The authors identified a total of 45 patients with SAVSs, including 2 cases of spinal arteriovenous malformation, 5 cases of perimedullary arteriovenous fistula (AVF), 31 cases of spinal dural AVF (SDAVF), and 7 cases of spinal epidural AVF (SEAVF). The crude incidence rate was 0.234 per 100,000 person-years for all SAVSs including those at the craniocervical junction (CCJ) level. The incidence rate of SDAVF and SEAVF combined increased with advancing age in men only. In a comparative analysis between upper and lower spinal SDAVF/SEAVF, hemorrhage occurred in 7/14 cases (50%) at the CCJ/cervical level and in 0/24 cases (0%) at the thoracolumbar level (p = 0.0003). Venous congestion appeared in 1/14 cases (7%) at the CCJ/cervical level and in 23/24 cases (96%) at the thoracolumbar level (p < 0.0001). CONCLUSIONS: The authors reported detailed incidence rates of SAVSs in Japan. There were some differences in clinical characteristics of SAVSs in the upper spinal levels and those in the lower spinal levels.

Mobile endovascular therapy for acute treatment of ruptured vertebral artery dissecting aneurysm in multiple hospitals.

BACKGROUND: The patients with ruptured vertebral artery dissecting aneurysm (rVADA) should be treated as early as possible because VADA carries extremely high risk of rebleeding in the acute phase. We have established a mobile endovascular strategy for the patients with rVADA between our flagship center and its affiliated local hospitals. We introduced and reviewed our mobile endovascular therapy in this study. METHODS: We retrospectively evaluated 98 consecutive patients who underwent endovascular surgery for rVADA from 2000 to 2018 at our institution or five affiliated hospitals. When each patient was initially transported to the local affiliated hospitals, neuroendovascular surgeons traveled directly to the affiliated hospital from the flagship center in order to treat the patient there. Clinical outcomes using modified Rankin Scale at 6 months after treatment, radiological results, and procedure-related complications were reviewed to justify our mobile endovascular strategy. RESULTS: All aneurysms were cured successfully by internal trapping. Favorable outcome was achieved in 61 patients (62.2%) even though 53 patients (54.1%) had presented with severe subarachnoid hemorrhage. Overall mortality rate, treatment-related mortality rate, and treatment related complication rate were 18.4% (18/98), 0%, and 16% (16/98), respectively. There were no differences in clinical and radiological outcomes between the patients treated in the flagship center and those who treated in the affiliated hospitals. Treatment in the affiliated hospital was not a predictive factor of unfavorable outcome in our multivariate analysis, and elderly age (≥ 60) was negatively associated with favorable outcome. CONCLUSIONS: Our results prove the efficacy and safety of mobile endovascular therapy for the treatment of rVADA in the ultra-acute stage. Mobile endovascular therapy may work well in the acute treatment of rVADAs in the certain circumstance.

Imaging findings of granulocyte colony-stimulating factor-producing tumors: a case series and review of the literature.

Granulocyte colony-stimulating factor (G-CSF)-producing tumors have an aggressive clinical course. Here, we report five cases of G-CSF-producing tumors and review the literature, focusing on imaging findings related to tumor-produced G-CSF. In addition to our cases, we identified 30 previous reports of G-CSF-producing tumors on which 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT, bone scintigraphy, or evaluation of bone marrow MR findings was performed. White blood cell count, serum C-reactive protein, and serum interleukin-6 were elevated in all cases for which these parameters were measured. G-CSF-producing tumors presented large necrotic masses (mean diameter 83.2 mm, range 17-195 mm) with marked FDG uptake (mean maximum standardized uptake value: 20.09). Diffuse FDG uptake into the bone marrow was shown in 28 of the 31 cases in which FDG-PET/CT was performed. The signal intensity of bone marrow suggested marrow reconversion in all seven MRI-assessable cases. Bone scintigraphy demonstrated no significant uptake, except in two cases with bone metastases. Splenic FDG uptake was increased in 8 of 10 cases in which it was evaluated. These imaging findings may reflect the effects of tumor-produced G-CSF. The presence of G-CSF-producing tumors should be considered in patients with cancer who show these imaging findings and marked inflammatory features of unknown origin.

Trends in Incidence of Intracranial and Spinal Arteriovenous Shunts: Hospital-Based Surveillance in Okayama, Japan.

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.

4-Hydroxyl-2-Nonenal Localized Expression Pattern in Retrieved Clots is Associated with Large Artery Atherosclerosis in Stroke Patients.

OBJECTIVES: The relationship between stroke etiology and clot pathology remains controversial. MATERIALS AND METHODS: We performed histological analysis of clots retrieved from 52 acute ischemic stroke patients using hematoxylin and eosin staining and immunohistochemistry (CD42b and oxidative/hypoxic stress markers). The correlations between clot composition and the stroke etiological group (i.e., cardioembolic, cryptogenic, or large artery atherosclerosis) were assessed. RESULTS: Of the 52 clots analyzed, there were no significant differences in histopathologic composition (e.g., white blood cells, red blood cells, fibrin, and platelets) between the 3 etiological groups (P = .92). By contrast, all large artery atherosclerosis clots showed a localized pattern with the oxidative stress marker 4-hydroxyl-2-nonenal (P < .01). From all 52 clots, 4-hydroxyl-2-nonenal expression patterns were localized in 28.8% of clots, diffuse in 57.7% of clots, and no signal in 13.5% of clots. CONCLUSIONS: A localized pattern of 4-hydroxyl-2-nonenal staining may be a novel and effective marker for large artery atherosclerosis (sensitivity 100%, specificity 82%).

A Patient with a Cavernous Sinus Dural Arteriovenous Fistula in Whom an Approach through the Jugular Venous Arch Involving Facial Vein Return Was Adopted.

Objective: We report the case of a cavernous sinus dural arteriovenous fistula (CSdAVF) treated by transvenous embolization (TVE) via the jugular venous arch (JVA) connecting bilateral superficial cervical veins. Case Presentation: A male patient in his 50s presenting with diplopia and headache was diagnosed with a CSdAVF. The first session of TVE resulted in incomplete obliteration of the fistula due to poor accessibility through the inferior petrosal sinus (IPS), and postoperative computed tomography angiography (CTA) disclosed a newly developed drainage route into the facial vein (FV) connecting to the anterior jugular vein (AJV) and the JVA. The patient underwent the second session of TVE through the JVA, FV, and the superior ophthalmic vein (SOV), and obliteration was achieved. Conclusion: There is a considerable variation in the anatomy of facio-cervical veins in patients with CSdAVF. Meticulous preoperative evaluation of the venous drainage route using modern diagnostic tools is indispensable to achieve successful results in patients with CSdAVF.

Feasibility and mid- to long-term results of endovascular treatment for portal vein thrombosis after living-donor liver transplantation.

PURPOSE: We aimed to evaluate mid- to long-term results of endovascular treatment for portal vein thrombosis (PVT) after living-donor liver transplantation (LDLT). METHODS: Thirty cases (14 males, 16 females; age range, 0.67-65 years) who underwent endovascular treatment including thrombolysis, angioplasty, stent placement, and/or collateral embolization for PVT after LDLT from 2001 to 2017 were retrospectively reviewed. Clinical and procedural data were collected and analyzed regarding the patency of the PVT site at the last follow-up date (PVT-free persistency) using Log-rank test. Results were considered statistically significant at P < 0.05. RESULTS: Median follow-up was 120 months. The technical success rate was 80% (n=24). Patency rates at 1 week and 1, 3, 6, 12, 36, and 60 months were 73%, 59%, 55%, 51%, 51%, 51%, and 51% for primary patency and 80%, 70%, 66%, 66%, 66%, 61%, and 61% for assisted patency after secondary endovascular treatment. PVT-free persistency rates regarding the subgroups were as follows: children under 12 years vs. adults, 50% vs. 68% (P = 0.42); acute vs. nonacute, 76% vs. 46% (P = 0.10); localized vs. extensive, 90% vs. 50% (P = 0.035); transileocolic approach vs. percutaneous-transhepatic approach, 71% vs. 54% (P = 0.39); and thrombolysis-based treatment vs. non-thrombolysis-based treatment, 71% vs. 44% (P = 0.12), respectively. Among technically successful cases, PVT-free persistency rate was 94% for those with hepatopetal flow in the peripheral portal vein vs. 17% for those without hepatopetal flow (P < 0.001). The only major complication occurring was pleural hemorrhage (n=1). Minor complications (i.e., fever) occurred in 18 patients (60%). CONCLUSION: In conclusion, mid- to long-term portal patency following endovascular treatment was approximately 50%-60% in PVT patients after LDLT. PVT site patency over three months after the first endovascular treatment, localized PVT, and hepatopetal flow in the peripheral portal vein were identified as key prognostic factors for mid- to long-term portal patency.

Utility of real-time image fusion technology in ultrasonography-guided fiducial marker implantation for stereotactic body radiation therapy for liver tumors.

BACKGROUND: Ultrasonography (US) is useful when implanting fiducial markers in the liver. However, the implant position is sometimes lost. Recently, real-time image fusion technology (Volume Navigation [V-navi]; GE Healthcare, Milwaukee, WI, USA) has been introduced as a technique for using images from different modalities, and its utility for fiducial marker implantation has been hypothesized. PURPOSE: To evaluate the utility of US-guided fiducial marker implantation in the liver using V-navi compared to conventional US. MATERIAL AND METHODS: We retrospectively reviewed 35 patients who underwent fiducial marker implantation for stereotactic body radiation therapy of liver tumors in 2013-2018. To avoid artifacts obscuring the tumor, the target point of implantation was set 10 mm cranial or caudal to the tumor. Marker implantation was then performed using US alone (US group, n = 24) or V-navi with computed tomography (CT) or magnetic resonance imaging (V-navi group, n = 11). Postprocedural CT was evaluated to determine technical success, distances between marker and either tumor surface or target point, and whether marker-induced artifacts obscured the tumor. Complications were also evaluated. Results were compared between groups. RESULTS: Technical success was obtained in 33 patients. Distance between the tumor and marker showed no significant difference between groups. Distance between target point and marker was shorter in the V-navi group (P = 0.0093). Tumor-obscuring artifacts were seen in 12 patients (V-navi group, n = 1; US group, n = 11; P = 0.055). The only complication was minor bleeding in the US group (n = 1). CONCLUSION: V-navi appears useful for US-guided fiducial marker implantation in the liver compared with conventional US.

Optimizing b-values for accurate depiction of pancreatic cancer with tumor-associated pancreatitis on computed diffusion-weighted imaging.

PURPOSE: To determine the optimal b-value for accurate depiction of pancreatic cancer (PC) in patients with active tumor-associated pancreatitis (TAP), using computed diffusion-weighted imaging (cDWI) with a range of b-values up to 3000 s/mm2. METHODS: The study protocol was approved by the institutional review board. We retrospectively analyzed 34 consecutive PC cases with active TAP who underwent pancreatectomy without preoperative therapy. Four cDWI datasets with b-values of 1500-3000 s/mm2 (cDWI1500-cDWI3000) were generated from the original DWI datasets with b-values of 0 and 1000 s/mm2 obtained using a 3-T scanner. Two board-certified radiologists evaluated images qualitatively (tumor conspicuity and total image quality), and another two board-certified radiologists placed regions of interest for quantitative evaluations (apparent diffusion coefficient [ADC] values of both lesions, contrast ratio [CR] of PC to active TAP, and volume ratio [VR] of PC to surgical specimen). RESULTS: As the b-value increased, tumor conspicuity improved significantly in cDWI2000 and cDWI2500 (P = 0.0121 and 0.0015, respectively), although total image quality decreased in all cDWIs compared with DWI1000 (P < 0.0001). Significantly lower ADC values were seen in PC (P < 0.0001). All cDWI groups showed positive correlation between the tumor conspicuity and ADC difference between PC and TAP. CR increased with the b-value, while VR decreased. Significant equivalence of VR to the surgical specimen was seen on cDWI2000 (P = 0.0031). CONCLUSION: Accurate depiction of PC was optimal with cDWI2000 in the presence of active TAP.

Practical Use of a Communication Application on Mobile Devices by Our Stroke Team.

Objective: To describe our 1-year experience of the practical use of a mobile communication application by our stroke team. Methods: The mobile Join application (Allm Inc., Tokyo, Japan) was introduced into our stroke team for the purpose of immediate sharing of the patient information. We analyzed the usage situation for 1 year after the introduction of Join, particularly its efficacy in improving the door-to-puncture time (D2P) for thrombectomy cases, and reported our inter-hospital collaboration with the use of Join. Results: The total number of events notified by Join was 337, and they included acute stroke potentially leading to reperfusion therapy in 23% (76 events), head trauma in 14%, brain hemorrhage in 12%, other infarction in 10%, subarachnoid hemorrhage in 8%, and the others in 34%. The information of the patients was shared among the team members before arrival to our hospital in 42% of acute stroke cases. Of 31 patients undergoing mechanical thrombectomy, the median interval between arrival and groin puncture for the directly transported patients with/without pre-hospital information was 77.5 min/87 min, respectively, whereas that of the patients transferred from primary hospitals with/without pre-hospital information was 19 min/71 min (p <0.0001), respectively, demonstrating the efficacy of information sharing in advance through Join in improving the timing of endovascular therapy. For inter-hospital collaboration using the telestroke system, we concluded the partnership agreement with three local primary hospitals by communication via Join at a reasonable cost. Conclusion: Active and effective utilization of the mobile Join application for communication by our stroke team was demonstrated, and it is expected to promote inter-hospital collaboration in stroke treatment.

Duodenal obstruction induced by retroperitoneal progression of bladder cancer: a report of two cases.

Bladder cancer usually forms a papillary structure. Progression along the cavity or membranous structures surrounding the bladder, rectum, or retroperitoneum without formation of a discrete mass is rare. We here present two patients with duodenal obstruction caused by retroperitoneal progression of bladder cancer, in both of whom computed tomography revealed bladder and rectal wall thickening with a malignant target sign, thickened mesorectal fascia with abnormal tissue stranding, and increased perirectal fat density. Both cancers progressed despite treatment, as indicated by faint abnormal tissue stranding and increased retroperitoneal fat density along the retromesenteric plane from the pelvis to the duodenum. Subsequently, both patients developed obstruction in the horizontal portion of the duodenum, still without formation of a mass lesion. These two patients highlight the challenges associated with retroperitoneal invasion by bladder cancer in the absence of a mass lesion and underscore the importance of considering cancer progression in patients with bowel obstruction, even when there is no obvious mass lesion and/or only minor retroperitoneal findings. Progression along the retromesenteric plane may be the key pathway via which progressive bladder cancer results in duodenal obstruction without or with a minor mass lesion.

Can the "pine-needle sign" on computed tomography be used to differentiate pulmonary arteriovenous malformation from its mimics? Analysis based on dynamic contrast-enhanced chest computed tomography in adults.

OBJECTIVES/PURPOSE: To determine the diagnostic value of morphological features on computed tomography (CT) in the differentiation of pulmonary arteriovenous malformation (pAVM) and its mimics. MATERIALS AND METHODS: We retrospectively examined 59 consecutive patients (109 lesions) with initially suspected or occult pAVM who underwent contrast-enhanced chest CT from January 2006 to June 2016. All lesions were divided into two groups based on their diagnosis: AVM (n=93) and non-AVM (n=16). The non-AVM group comprised patients with an anomalous unilateral single pulmonary vein and congenital pulmonary venous atresia. Two board-certified radiologists reviewed the CT images and achieved consensus. Paired abnormal vessels were assessed with respect to their configuration, direction and continuity with the hilum, location, angle between them, and dilation ratio. RESULTS: All pAVM lesions had parallel, straight-running, paired abnormal vessels; most of the vessels ran through the identical segment. Conversely, in the non-AVM group, paired abnormal vessels did not run in parallel but detoured to the hilum through different segments from each other (i.e., the configuration, direction and continuity with the hilum and the location of the vessels were all significantly different between the two groups). The angle between the paired abnormal vessels was significantly narrower in the AVM group. The dilation ratio was not significantly different between the two groups. CONCLUSION: Morphological features can be useful in the differentiation of pAVM and its mimics without contrast-enhanced CT to directly visualize the connection between the abnormal and normal pulmonary vessels. Pulmonary AVMs characteristically had a narrow angle between the two vessels, appearing like a pair of pine-needle leaves.

Combined gene therapy with vascular endothelial growth factor plus apelin in a chronic cerebral hypoperfusion model in rats.

OBJECTIVE The aim of this study was to evaluate whether combined gene therapy with vascular endothelial growth factor (VEGF) plus apelin during indirect vasoreconstructive surgery enhances brain angiogenesis in a chronic cerebral hypoperfusion model in rats. METHODS A chronic cerebral hypoperfusion model induced by the permanent ligation of bilateral common carotid arteries (CCAs; a procedure herein referred to as "CCA occlusion" [CCAO]) in rats was employed in this study. Seven days after the CCAO procedure, the authors performed encephalo-myo-synangiosis (EMS) and injected plasmid(s) into each rat's temporal muscle. Rats were divided into 4 groups based on which plasmid was received (i.e., LacZ group, VEGF group, apelin group, and VEGF+apelin group). Protein levels in the cortex and attached muscle were assessed with enzyme-linked immunosorbent assay (ELISA) on Day 7 after EMS, while immunofluorescent analysis of cortical vessels was performed on Day 14 after EMS. RESULTS The total number of blood vessels in the cortex on Day 14 after EMS was significantly larger in the VEGF group and the VEGF+apelin group than in the LacZ group (p < 0.05, respectively). Larger vessels appeared in the VEGF+apelin group than in the other groups (p < 0.05, respectively). Apelin protein on Day 7 after EMS was not detected in the cortex for any of the groups. In the attached muscle, apelin protein was detected only in the apelin group and the VEGF+apelin group. Immunofluorescent analysis revealed that apelin and its receptor, APJ, were expressed on endothelial cells (ECs) 7 days after the CCAO. CONCLUSIONS Combined gene therapy (VEGF plus apelin) during EMS in a chronic cerebral hypoperfusion model can enhance angiogenesis in rats. This treatment has the potential to be a feasible option in a clinical setting for patients with moyamoya disease.

Cerebral Infarction Arising from Takotsubo Cardiomyopathy: Case Report and Literature Review.

Although most patients with takotsubo cardiomyopathy have a favorable outcome, complications are not uncommon. Recent studies have reported an increase in incidence of cardioembolic complications; however, the association between takotsubo cardiomyopathy and stroke, in particular thromboembolic cerebral infarction, remains unclear. We reported a 44-year-old woman who had a cerebral infarction resulting from takotsubo cardiomyopathy. She had felt chest discomfort a few days prior to infarction, and later developed left hemiparesis. Head magnetic resonance imaging (MRI) revealed acute infarction in the right insular cortex and occlusion of the right middle cerebral artery at the M2 segment. Echocardiogram revealed a takotsubo-like shape in the motion of the left ventricular wall, and coronary angiography showed neither coronary stenosis nor occlusion. Cerebral infarction resulting from takotsubo cardiomyopathy was diagnosed and treatment with anticoagulant was started. MRI on the eighth day after hospitalization showed recanalization of the right middle cerebral artery and no new ischemic lesions. The findings of the 19 previously published cases who had cerebral infarction resulting from takotsubo cardiomyopathy were also reviewed and showed the median interval between takotsubo cardiomyopathy and cerebral infarction was approximately 1 week and cardiac thrombus was detected in 9 of 19 patients. We revealed that thromboembolic events occurred later than other complications of takotsubo cardiomyopathy and longer observation might be required due to possible cardiogenic cerebral infarction. Anticoagulant therapy is recommended for patients with takotsubo cardiomyopathy with cardiac thrombus or a large area of akinetic left ventricle.

Risk of rupture of unruptured cerebral aneurysms in elderly patients.

OBJECTIVES: The aim of this study was to identify risk factors for rupture of unruptured cerebral aneurysms (UCAs) in elderly Japanese patients aged 70 years or older. METHODS: The participants included all patients 70 years of age or older in 3 prospective studies in Japan (the Unruptured Cerebral Aneurysm Study of Japan [UCAS Japan], UCAS II, and the prospective study at the Jikei University School of Medicine). A total of 1,896 patients aged 70 years or older with 2,227 UCAs were investigated. The median and mean follow-up periods were 990 and 802.7 days, respectively. RESULTS: The mean aneurysm size was 6.2 ± 3.9 mm. Sixty-eight patients (3.6%) experienced subarachnoid hemorrhage during the follow-up period. Multivariable analysis per patient revealed that in patients aged 80 years or older (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.16-3.49, p = 0.012), aneurysms 7 mm or larger (HR, 3.08; 95% CI, 1.35-7.03, p = 0.007 for 7-9 mm; HR, 7.82; 95% CI, 3.60-16.98, p < 0.001 for 10-24 mm; and HR, 43.31; 95% CI, 12.55-149.42, p < 0.001 for ≥25 mm) and internal carotid-posterior communicating artery aneurysms (HR, 2.45; 95% CI, 1.23-4.88, p = 0.011) were independent predictors for UCA rupture in elderly patients. CONCLUSIONS: In our pooled analysis of prospective cohorts in Japan, patient age and aneurysm size and location were significant risk factors for UCA rupture in elderly patients.