Association between Living Conditions and the Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults.

Objective In recent decades, living conditions have changed drastically. However, there are few data regarding the interaction between living conditions and the risk of ischemic stroke (IS) in young adults. The present study explored the association between living conditions or marital status and the risk factors, etiology, and outcome of IS in young adults. Methods We prospectively enrolled patients with incident IS who were 20-49 years old from 37 clinical stroke centers. We collected the demographic data, living conditions, marital status, vascular risk factors, disease etiology, treatment, and outcomes at discharge. A comparison group was established using the official statistics of Japan. We categorized patients into the two groups based on living conditions: solitary group and cohabiting group. Clinical characteristics were then compared between living conditions. Results In total, 303 patients were enrolled (224 men; median age at the onset: 44 years old). Significant factors associated with the incidence of IS were as follows: solitary status, body mass index >30 kg/m2, current smoking, heavy alcohol consumption, hypertension, diabetes mellitus, and dyslipidemia. Furthermore, in the solitary group, the proportions of men, unmarried individuals, and current smokers were significantly higher than in the cohabiting group. In addition, poor outcomes (modified Rankin Scale ≥4) of IS were more common in the solitary group than in the cohabiting group. Conclusion Our study showed that not only conventional vascular risk factors but also living conditions, especially living alone while unmarried, were independent risk factors for IS in young adults.

Characteristics of Ischemic Versus Hemorrhagic Stroke in Patients Receiving Oral Anticoagulants: Results of the PASTA Study.

Objective Limited data exist regarding the comparative detailed clinical characteristics of patients with ischemic stroke (IS)/transient ischemic attack (TIA) and intracerebral hemorrhage (ICH) receiving oral anticoagulants (OACs). Methods The prospective analysis of stroke patients taking oral anticoagulants (PASTA) registry, a multicenter registry of 1,043 stroke patients receiving OACs [vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulant (NOACs)] across 25 medical institutions throughout Japan, was used. Univariate and multivariable analyses were used to analyze differences in clinical characteristics between IS/TIA and ICH patients with atrial fibrillation (AF) who were registered in the PASTA registry. Results There was no significant differences in cardiovascular risk factors, such as hypertension, diabetes mellitus, dyslipidemia, smoking, or alcohol consumption (all p>0.05), between IS/TIA and ICH among both NOAC and VKA users. Cerebral microbleeds (CMBs) [odds ratio (OR), 4.77; p<0.0001] were independently associated with ICH, and high brain natriuretic peptide/N-terminal pro B-type natriuretic peptide levels (OR, 1.89; p=0.0390) were independently associated with IS/TIA among NOAC users. A history of ICH (OR, 13.59; p=0.0279) and the high prothrombin time-international normalized ratio (PT-INR) (OR, 1.17; p<0.0001) were independently associated with ICH, and a history of IS/TIA (OR, 3.37; 95% CI, 1.34-8.49; p=0.0101) and high D-dimer levels (OR, 2.47; 95% CI, 1.05-5.82; p=0.0377) were independently associated with IS/TIA among VKA users. Conclusion The presence of CMBs, a history of stroke, natriuretic peptide and D-dimer levels, and PT-INR may be useful for risk stratification of either IS/TIA or ICH development in patients with AF receiving OACs.

Revascularization to the ACA: effectiveness and variation of the STA-RAG-A3 bonnet bypass.

BACKGROUND: The effectiveness of bypass surgery in patients with atherothrombotic ischemia in the anterior cerebral artery (ACA) domain remains unclear. In this study, three cases with ischemia in the ACA territory underwent revascularization surgery using superficial temporal artery (STA)-radial artery graft (RAG)-A3 (pericallosal artery) bonnet bypass. Herein, we discuss the effectiveness and variations of this approach. METHODS: Among 182 consecutive patients with atherothrombotic ischemic stroke admitted to the NTT Medical Center, Tokyo, from April 2017 to May 2021, three patients with hemodynamic insufficiency in the extensive ACA territory beyond the recent infarct area were treated using STA-RAG-A3 bonnet bypass. RESULTS: One patient with bilateral severe cerebral blood flow (CBF) deficiency required additional A3-A3 and STA-middle cerebral artery single bypass in conjunction with STA-RAG-A3 bypass. There were no complications associated with the surgical procedure. The patients' hemodynamic study results and neurocognitive performances improved dramatically after surgery. CONCLUSION: Our results suggest the efficacy of STA-RAG-A3 bypass for atherothrombotic ACA ischemia. However, because the number of cases was too small to generalize our results, more cases and thorough pre- and postoperative hemodynamic studies are necessary to prove the validity of the approach.

Risk factors, etiology, and outcome of ischemic stroke in young adults: A Japanese multicenter prospective study.

PURPOSE: This study aimed to evaluate the risk factors, etiology, and outcomes of ischemic stroke (IS) in Japanese young adults. METHODS: This was a prospective multicenter study. We enrolled patients aged 16 to 55 years with IS within seven days of the onset of symptoms. We assessed the demographic data, risk factors, stroke etiology, and outcome at discharge. The clinical characteristics were compared between sexes and among age groups. RESULTS: We prospectively enrolled 519 patients (median age, 48 years: 139 females). The mean National Institute of Health Stroke Scale score was 3.6 ± 0.2. The most common risk factors were hypertension (HT) (55%), dyslipidemia (DL) (47%), and current smoking (42%). Body mass index, incidence of current smoking, and heavy alcohol consumption were higher in males. The prevalence of current smoking, HT, DL, and diabetes mellitus increased with aging. The most common etiologic subgroup of IS was small vessel disease (145/510, 28%). Intracranial arterial dissection (IAD) was the most common among the other determined causes (56/115, 49%). The outcome at discharge was relatively good (mRS 0-1, 71.7%); however, poor outcome (mRS ≥ 4) was observed at an incidence of 9.5%. CONCLUSIONS: Most young adults with IS had modifiable risk factors, of which prevalence increased with age. This emphasizes lifestyle improvement to prevent IS in the young population. Furthermore, we indicated that the incidence rate of IAD was high among the other determined causes.

Cerebral amyloid-ß-related angiitis without cerebral microbleeds in a patient with subarachnoid hemorrhage.

Amyloid-ß-related angiitis (ABRA), a subtype of cerebral amyloid angiopathy (CAA), is vasculitis occurring in relation to amyloid-ß (Aß) deposition in the walls of intracranial blood vessels. ABRA is presumed to be caused by some immune response to the deposited Aß. An 81-year-old man on oral anticoagulant therapy complained of headache, nausea, and difficulty with standing after a head injury. Head computed tomography revealed subcortical bleeding in the right temporoparietal lobe, and 3 days after admission, magnetic resonance imaging (MRI) showed subarachnoid hemorrhage (SAH) around the hematoma. Cerebral microbleeds, a characteristic of CAA, were not detected on MRI. On worsening of his symptoms, intracranial brain biopsy and hematoma removal were performed. Intraoperative rapid diagnosis with a frozen section suspected vasculitis, which enabled the prompt initiation of steroid therapy. He was pathologically diagnosed with ABRA (granulomatous angiitis) using a formalin-fixed paraffin-embedded section. Vasculitis was prominent around blood vessels in the pia matter covering the cerebrum. In this case, the inflammatory cells seemed to appear via the subarachnoid space following cerebral hemorrhage and SAH. ABRA seemed to be developed by intracranial hemorrhage in this case.

Cerebral Embolism Caused by Thrombus in the Pulmonary Vein Stump after Left Lower Lobectomy: A Case Report and Literature Review.

Cerebral embolism after left upper lobectomy caused by a thrombus in the pulmonary vein stump (PVS) is a serious complication. However, it is unclear if cerebral embolism can develop after other types of lobectomy. We present a case of a 68-year-old man with cerebral embolism after left lower lobectomy with a longer PVS than normal. There were no clinically suspected sources for the thrombus except for the PVS. This thrombus seemed to have formed in the PVS. The endovascularly removed thrombus contained scattered nuclear debris around neutrophils, suggesting a physiological response caused by tissue injury.

Thrombus Reformation in the Pulmonary Vein Stump Confirmed 16 Months After Cerebral Embolism on the Day After Left Upper Lobectomy for Lung Cancer.

Cerebral embolism is a very serious complication after lung cancer surgery. In such cases, cerebral embolism is caused by a thrombus formed in the pulmonary vein stump. Most such cases have been reported to occur within 10 days after left upper lobectomy. The patients were treated with anticoagulation therapy to prevent the recurrence of cerebral embolism, and recurrence or thrombus reformation has not been reported to the best of our knowledge. We present a 68-year-old man with a cerebral embolism detected on the day after left upper pulmonary lobectomy for lung cancer. The patient was treated with unfractionated heparin and his neurological symptoms improved. Heparin treatment was subsequently changed to aspirin for the prevention of recurrence; however, thrombus formation in the vein stump was asymptomatically confirmed 16 months after the surgery by contrast-enhanced computed tomography. This is the first case to our knowledge of thrombus reformation in the pulmonary vein stump after a cerebral embolism associated with lung cancer surgery. In our case, anticoagulation therapy was not continued to prevent recurrence, and antiplatelet therapy was performed instead, which might be associated with the thrombus reformation.

Multiple Cerebral Infarctions in a Patient with Adenomyosis on Hormone Replacement Therapy: A Case Report.

A 59-year-old woman was admitted to our hospital because of repeated episodes of bilateral hand weakness. She had a 10-year history of combined estrogen-progestin therapy for menopausal symptoms. Magnetic resonance imaging on admission showed multiple hyperintense lesions in bilateral cerebral and cerebellar cortices on diffusion-weighted imaging. Transesophageal echocardiography showed thrombus formation on the aortic valve and moderate aortic insufficiency. Laboratory test demonstrated elevated CA125 (334.8 U/mL) and D-dimer (7.0 µg/mL) levels. Trousseau's syndrome (cancer-related hypercoagulation) was considered, but various examinations showed only uterine adenomyosis and no evidence of cancer. Multiple cerebral infarctions were considered to be caused by Trousseau's syndrome-like condition associated with uterine adenomyosis. CA125 and coagulation markers should be measured in adenomyosis patients treated with hormone replacement therapy, because a mucinous tumor and coagulation markers may be good markers for the risk of thromboembolism in such patients.

Low free triiodothyronine predicts poor functional outcome after acute ischemic stroke.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the association of admission serum thyroid hormone concentration with clinical characteristics and functional outcomes in patients after acute ischemic stroke. METHODS: We retrospectively enrolled 398 consecutive patients admitted to our stroke center between July 2010 and April 2012. Serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were evaluated upon admission. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) upon admission and the modified Rankin Scale (mRS) upon discharge. Poor outcome was defined as a mRS score of 3-5 or death (mRS score 6). Separate analyses were conducted according to outcome and quartile serum FT3 concentration. RESULTS: In total, 164 patients (41.2%) demonstrated a poor outcome. Age, male gender, blood glucose level, arterial fibrillation, dyslipidemia, smoking, NIHSS score, cardioembolic stroke type, and periventricular hyperintensities, but not FT4 or TSH, were significantly associated with poor functional outcome. Furthermore, poor functional outcome was independently associated with low FT3 (<2.29pg/mL). In comparisons between FT3 quartiles (Q1 [≤2.11pg/mL], Q2 [2.12-2.45pg/mL], Q3 [2.46-2.77pg/mL], Q4 [≥2.78pg/mL]), patients with poor outcomes were more frequent in Q1 than in Q4 after multivariate adjustment. Death was more frequent in Q1 than in Q4 after adjustment for risk factors and comorbidities, but this difference was non-significant after additional adjustment for age and NIHSS score. CONCLUSIONS: Our data suggest that a lower FT3 value upon admission may predict a poor functional outcome in patients with acute ischemic stroke. Further large-scale prospective studies are required to clarify the role of thyroid hormone in the acute phase of ischemic stroke.

Relative risk values of age, acrolein, IL-6 and CRP as markers of periventricular hyperintensities: a cross-sectional study.

OBJECTIVE: Brain white matter hyperintensities can be divided into periventricular hyperintensity (PVH) and deep-and-subcortical white matter hyperintensity (DSWMH); the former contributes more to cognitive dysfunction and infarction risk. We conducted the present investigation to define the relationship between PVH and DSWMH. DESIGN: Cross-sectional study. SETTING: University hospital. PARTICIPANTS: We prospectively enrolled 228 healthy Japanese volunteers with relative risk values (RRVs) >0.5. PRIMARY OUTCOME MEASURES: We investigated whether it is possible to use the RRV to predict PVH and DSWMH. RESULTS: Among 228 volunteers, 103 (45.1%) and 157 (68.8%) exhibited PVH and DSWMH, respectively. Age, body mass index and PVH were significant independent determinants of RRV. A significant OR for PVH was noted in the highest RRV tertile compared with the lowest, after adjusting for potential confounding factors. A significant OR for high predicted PVH risk was found for RRV levels as well. CONCLUSIONS: Elevated RRV levels were significantly associated with increased predicted PVH, suggesting that measuring the plasma protein-conjugated acrolein, interleukin 6 and C reactive protein levels may be useful for identifying Japanese at high risk for PVH.

Acute vertebral artery origin occlusion leading to basilar artery thrombosis successfully treated by angioplasty with stenting and thrombectomy.

Few reports have described the successful treatment of stroke caused by acute vertebral artery (VA) origin occlusion by endovascular surgery. We describe the case of a 68-year-old man who experienced stroke due to left acute VA origin occlusion. Cerebral angiography showed that the left VA was occluded at its origin, the right VA had hypoplastic and origin stenosis, and the basilar artery was occluded by a thrombus. The VA origin occlusion was initially passed through with a 0.035-inch guide wire. An angioplasty was performed, and a coronary stent was appropriately placed. The VA origin was successfully recanalized. A balloon-assisted guiding catheter was navigated through the stent and a thrombectomy was performed using the Penumbra system. The patient's symptoms gradually improved postoperatively. Balloon-assisted catheter guidance through a vertebral artery stent permitted a successful thrombectomy using the Penumbra system and may be useful for treating stroke due to VA origin occlusion.

In vivo monitoring of arterially transplanted bone marrow mononuclear cells in a rat transient focal brain ischemia model using magnetic resonance imaging.

OBJECTIVES: Intra-arterial transplantation of bone marrow mononuclear cells (BMMCs) effectively improves neuronal function and limits the infarct size. We monitored the fate of BMMCs labeled with super paramagnetic iron oxide (SPIO) until 7 days after the transplantation using high-field magnetic resonance imaging (MRI). METHODS: Male Sprague-Dawley rats were subjected to 90-minute focal ischemia using the intraluminal suture technique followed by transplantation of 1 × 10(7) BMMCs or vehicle only via the ipsilateral carotid artery immediately after reperfusion. Autologous BMMCs were labeled with SPIO by electroporation prior to ischemia. MRI studies were performed at 1 hour, 24 hours, 3 days, and 7 days after reperfusion on each rat. The total infarct volume and the volume of negative dots were measured on T2-weighted images and T2*-weighted images, respectively. RESULTS: One hour after BMMC transplantation, we confirmed wide spread distribution of BMMCs in the ischemic hemisphere as a negative dot. The volume of negative dot normalized by hemispheric volume decreased rapidly and was seldom seen at the seventh day after transplantation. The infarct volume was significantly smaller in the transplanted group than the vehicle group at 24 hours and 7 days after reperfusion. DISCUSSION: The present study established In vivo monitoring of intra-arterial transplanted SPIO-labeled BMMCs immediately after reperfusion using MRI of a rat transient focal ischemia model. The accumulation of BMMCs in ischemic lesion at the acute stage of ischemia can be part of the conditions to limit the infarct size.

An unusual cerebral air embolism developing within the posterior circulation territory after a needle lung biopsy.

We herein report the case of a 75-year-old woman with a paradoxical cerebral air embolism (CAE). She developed a bilateral visual disturbance at the time of needle puncture during a computed tomography (CT)-guided percutaneous needle lung biopsy in the face down position. The air density within the descending aorta on chest CT suggested the presence of a cerebral air embolism. Brain MRI demonstrated increased signal intensity in the bilateral occipital lobes on diffusion-weighted images. Usually, CAE occurs predominantly in the right hemisphere for anatomical reasons. The face down position and the anatomical features of the right subclavian artery, which diverges backward from the brachiocephalic artery, might explain such a unique distribution of CAE in this patient.

Analysis of ischemic cerebral lesions using 3.0-T diffusion-weighted imaging and magnetic resonance angiography after revascularization surgery for ischemic disease.

BACKGROUND: Cerebral revascularization surgery (CRS) is increasingly recognized as an important component in the treatment of complex cerebral vascular disease and tumors. CRS requires that the incidence of perioperative neurological complications should be minimized, because CRS for ischemic disease is often not the goal of treatment, but rather a prophylactic surgery. CRS carries the risk of focal postoperative neurological deficits. Little has been established concerning mechanisms of post-CRS ischemia. We used 3.0-T diffusion-weighted magnetic resonance imaging (DWI) and magnetic resonance angiography (MRA) to analyze the incidence and mechanism of ischemic lesions. METHODS: We studied the anterior circulation territory after 20 CRS procedures involving 33 vascular anastomosis procedures (13 double anastomoses and 7 single anastomoses) in 12 men and 8 women between June 2007 and October 2011. The operations included single or double superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis to treat internal carotid artery/MCA occlusions or severe MCA stenosis. A combined STA-MCA anastomosis and indirect bypass were performed for moyamoya disease. Postoperative DWI and MRA were obtained in all patients between 24 and 96 h after surgery to detect thromboembolism, hypoperfusion, or procedural ischemic complications and vasospasms of the donor STA. RESULTS: Follow-up DWI and MRA were carried out 1.8±0.6 days after CRS (range, 1-4 days). Temporary occlusion time for anastomoses averaged 18.9 min (range, 16-32 min). Asymptomatic new hyperintensities occurred in the ipsilateral hemisphere of 2 patients on postoperative DWI (10% patients/6.0% anastomoses), and 1 moyamoya patient (5.0% patients/3.0% anastomoses) developed a symptomatic hyperintensity in the ipsilateral occipital lobe in response to the operation. Two abnormal small (<5 mm) cortical DWI lesions were caused by sacrifices of a small branch of the recipient MCA. CONCLUSION: This study is the first postoperative 3.0-T DWI study of CRS and related clinical events. The incidence of symptomatic postoperative DWI abnormalities was restricted to 1 moyamoya patient representing 5.0% of total patients and 3.0% anastomoses. Although some postoperative DWI abnormalities occurred, CRS was found to be safe with a low risk of symptomatic ischemia.

NMR structure of the N-terminal domain of SUMO ligase PIAS1 and its interaction with tumor suppressor p53 and A/T-rich DNA oligomers.

A member of the PIAS (protein inhibitor of activated STAT) family of proteins, PIAS1, have been reported to serve as an E3-type SUMO ligase for tumor suppressor p53 and its own. It also was proposed that the N-terminal domain of PIAS1 interacts with DNA as well as p53. Extensive biochemical studies have been devoted recently to understand sumoylations and its biological implications, whereas the structural aspects of the PIAS family and the mechanism of its interactions with various factors are less well known to date. In this study, the three-dimensional structure of the N-terminal domain (residues 1-65) of SUMO ligase PIAS1 was determined by NMR spectroscopy. The structure revealed a unique four-helix bundle with a topology of an up-down-extended loop-down-up, a part of which the helix-extended loop-helix represented the SAP (SAF-A/B, Acinus, and PIAS) motif. Thus, this N-terminal domain may be referred to as a four-helix SAP domain. The glutathione S-transferase pull-down assay demonstrated that this domain possesses a binding ability to tumor suppressor p53, a target protein for sumoylation by PIAS1, whereas gel mobility assays showed that it has a strong affinity toward A/T-rich DNA. An NMR analysis of the four-helix SAP domain complexed with the 16-bp-long DNA demonstrated that one end of the four-helix bundle is the binding site and may fit into the minor groove of DNA. The three-dimensional structure and its binding duality are discussed in conjunction with the biological functions of PIAS1 as a SUMO ligase.