Yuta Hagiwara

Secondary Prevention of New Vascular Events with Lifestyle Intervention in Patients with Noncardioembolic Mild Ischemic Stroke: A Single-Center Randomized Controlled Trial

Background: Lifestyle modification is associated with a substantially decreased risk of cardiovascular events. However, the role of lifestyle intervention for secondary prevention in patients with noncardioembolic ischemic stroke is inadequately defined. We assessed the hypothesis that lifestyle intervention can reduce the onset of new vascular events in patients with noncardioembolic mild ischemic stroke. Methods: We conducted an observer-blind randomized controlled trial that enrolled 70 patients (48 men, mean age 63.5 years) with acute noncardioembolic mild ischemic stroke. The patients were allocated in equal numbers to a lifestyle intervention group or a control group. We performed lifestyle interventions, which comprised exercise training, salt restriction and nutrition advice for 24 weeks. Then all patients were prospectively followed up for occurrence of the primary endpoints, including hospitalization due to stroke recurrence and the onset of other vascular events. We also evaluated systolic blood pressure (SBP) at the clinic and at home, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hemoglobin A1c (HbA1c) and high-sensitivity C-reactive protein (hs-CRP) to compare the efficacy of the lifestyle interventions. Results: This trial was terminated earlier than expected because of the prespecified early stopping rule for efficacy. After the 24-week intervention period, the intervention group showed a significant increase in daily physical activity and a significant decrease in salt intake (physical activity, p = 0.012; salt intake, p < 0.001), with a significant difference between the randomized groups (physical activity, p < 0.001; salt intake, p = 0.018). Similarly, blood pressure was decreased and the HDL-C levels were increased in the intervention group (SBP, p < 0.001; HDL-C, p = 0.018), with significant differences between the randomized groups (SBP, p < 0.001; HDL-C, p = 0.022). In contrast, LDL-C, HbA1c and hs-CRP tended to decrease in the intervention group, but this decrease did not achieve significance. After a median follow-up period of 2.9 years, 12 patients allocated to the control group and 1 patient in the lifestyle intervention group experienced at least 1 vascular event. A sequential plans analysis indicated the superiority of the lifestyle intervention in interim analysis. Kaplan-Meier survival curves after the log-rank test showed a significant prognostic difference between the randomized groups (p = 0.005). Conclusions: Lifestyle intervention with appropriate medication is beneficial for reducing the incidence of new vascular events and improving vascular risk factors in patients with noncardioembolic mild ischemic stroke.

Effects of Edaravone, a Free Radical Scavenger, on Circulating Levels of MMP-9 and Hemorrhagic Transformation in Patients with Intravenous Thrombolysis Using Low-dose Alteplase

BACKGROUND Matrix metalloproteinase-9 (MMP-9) plays a key role for the blood-brain barrier disruption and intravenous tissue plasminogen activator (iv-tPA) therapy increases MMP-9. Edaravone, a free radical scavenger, reduces MMP-9-related blood-brain barrier disruption. We aimed to investigate whether edaravone would suppress the MMP-9 increase after iv-tPA using low-dose alteplase (0.6 mg/kg). SUBJECTS Patients hospitalized within 12 hours after ischemic stroke onset between April 2008 and June 2013 were retrospectively examined. Patients with slight deficits (National Institutes of Health Stroke Scale score ≤ 4), stroke caused by arterial dissection, severe inflammatory disease or autoimmune disease, or regular use of steroid were excluded. Serum concentrations of high-sensitivity C-reactive protein, interleukin-6, MMP-2, and MMP-9 were serially measured at admission, after 24 hours, day 7, and day 14. General linear models were used to compare changes in concentrations of these biomarkers over time. RESULTS A total of 63 patients (38 men, aged 74.48 ± 13.8 years) were studied. Patients were divided into 2 groups according to the iv-tPA therapy, that is, tPA group (n = 32) and non-tPA group (n = 31). Edaravone was administered routinely except for contraindication (90.6% in the tPA group and 87.1% in the non-tPA group). Significant interaction of group × time factor was observed only in MMP-9 concentrations by repeated-measure analysis of variance (P = .004). Association between iv-tPA therapy and subsequent hemorrhagic transformation was highly significant, but MMP-9 concentrations at any point did not predictive of subsequent hemorrhagic transformation (area under the receiver operating characteristic curve, .681). CONCLUSIONS Low-dose iv-tPA increases MMP-9 concentration even in combination with Edaravone. The effect of higher dosage of Edaravone on circulating MMP-9 concentration and subsequent hemorrhagic transformation should be investigated.

Impact of Life and Family Background on Delayed Presentation to Hospital in Acute Stroke

The over-65 population stands at 29 million, more than 20% of the total population in Japan. This is the highest rate in the world. One-person households and older couple households will be increasing. The aim of the present study was to identify whether life and family background are significant factors for delayed presentation to hospital after stroke onset. A total of 253 patients (mean age, 70.7 ± 13.2 years) with stroke was examined. Patients who presented to hospital within 3 hours of onset were categorized as the early presentation group, and the other patients were categorized as the late presentation group. Life and family background were classified into 3 categories, namely 1-person households, 2-person households, and patients living with 3 or more persons. Two-person households were further subdivided by the age of family members. Multivariate logistic regression analysis demonstrated that 1-person households (odds ratio [OR]: 2.980, 95% confidence interval [CI]: 1.108-8.011) and 2-person households with individuals 65 years and older (OR: 3.059, 95% CI: 1.297-7.217) were significant independent factors for delayed presentation, in addition to stroke subtype, time of stroke onset, and route of admission. Onset-to-door time in patients with night-time onset was significantly different among different types of households. Significant delay was demonstrated in 2-person households with 2 individuals 65 years and older compared with that in patients living with 3 or more persons (P = .038). Our findings show that delayed presentation to hospital is more likely in stroke patients living in an elderly couple household, especially those with evening onset in an aging society.

Specific Needs for Telestroke Networks for Thrombolytic Therapy in Japan

The concept of telestroke networks has been proposed to overcome regional disparities in stroke treatment. Such networks do not yet operate in Japan. We aimed to determine the specific needs for telestroke networks and to estimate the effects on the number of thrombolytic therapies. Five of the 47 Japanese prefectures with various population densities to estimate the nationwide effect of telestroke networks were selected. The questionnaire survey was administered at hospitals in these prefectures that are authorized to admit patients with acute stroke. Low-volume hospitals that annually treated fewer than 12 patients with acute stroke had never used tissue plasminogen activator (tPA). The number of days when telestroke support might have been needed varied depending on the size of the population aged 65 years or older within a 30-minute-driving-time area of a hospital and the annual number of patients treated within 3 hours of onset. The geographic information system analysis showed that .6%-8.3% of the population lived in areas where they could not reach a hospital for acute stroke treatment within 60 minutes. If 24/7 full telestroke support was introduced to the existing hospitals, 6.8-69.3 more patients could be treated by intravenous (IV) tPA annually. These numbers exceeded the estimated annual increases of .8-13.7 more patients if a drip-and-ship telestroke network was introduced into an underserved area outside the 60-minute-driving-time area. This study uncovered that many Japanese stroke hospitals, especially low-volume facilities located in rural areas, do not perform IV tPA therapy in 24/7 fashion and telestroke support to these hospitals may be highly effective compared with the drip-and-ship network in an underserved area.

A case in which contrast-enhanced transoral carotid ultrasonography was useful for pre- and post-procedural evaluation in carotid artery stenting

Contrast-enhanced transoral carotid ultrasonography (CETOCU) is a novel examination modality that is superior to other modalities in the cases of pseudo-occlusion with severe arteriosclerotic stenosis of the distal internal carotid artery (ICA), and is also useful for noninvasively evaluating changes over time in the vessel distal to the stent following carotid artery stenting (CAS). We report a case of a patient who we evaluated with CETOCU for a pseudo-occlusive ICA before and after CAS.

Contrast‐enhanced transoral carotid ultrasonography for the evaluation of a long stenotic lesion in the internal carotid artery

Contrast‐enhanced transoral carotid ultrasonography (CETOCU) is a novel modality for imaging the distal extracranial internal carotid artery, which is not possible with conventional carotid ultrasonography. We present a representative case that demonstrates the usefulness of CETOCU.

Intraplaque Microvascular Flow Signal in Superb Microvascular Imaging and Magnetic Resonance Imaging Carotid Plaque Imaging in Patients with Atheromatous Carotid Artery Stenosis

Carotid artery atherosclerosis is one of the major risk factors for ischemic stroke. Intraplaque neovascularization (IPN) is one of the steps toward the development of vulnerable plaque. Superb microvascular imaging (SMI) is a new ultrasonographic technique for visualizing low-velocity and microvascular flow by clutter suppression to extract flow signals from large to small vessels and enables visualization of intraplaque microvascular flow (IMVF) without echo contrast media. We aimed to investigate the association between IMVF signal in SMI and MRI plaque imaging among patients with atherosclerotic carotid stenosis. We prospectively enrolled patients (>18 years old) with mild to severe carotid stenosis (more than 50% in cross-sectional area) diagnosed by carotid ultrasonography between August 2017 and April 2018, irrespective of sex and history of stroke. A total of 40 patients (31 men, 9 women; mean age, 75.1 ± 10.0 years) were enrolled. SMI revealed IPN findings in 21 patients. SMI clearly visualized the direction of pulsatile flow movement in microvessels and IPN was easily classified into the two types of Type V (n=2) and Type E (n=19). Multivariate logistic regression analysis presented that microvascular flow signal in carotid plaque on SMI was identified as a significant predictor of intraplaque hemorrhage as evaluated by MRI (OR, 8.46; 95%CI, 1.44-49.9; p=0.018). This study demonstrated a significant association between the presence of IMVF signal in SMI and intraplaque hemorrhage characterized by high-intensity lesions on MRI T1-FFE images.

The utility of superb microvascular imaging for the detection of deep vein thrombosis

Superb microvascular imaging (SMI) reduces motion artifacts significantly and allows visualization of low-velocity blood flow in vessels; thus, thrombi are clearly demonstrated compared to conventional B-mode and color Doppler imaging. Ultrasonographic images of the lower extremities of a 69-year-old woman with acute ischemic stroke complicated with deep vein thrombosis (DVT) are presented. Because SMI allows visualization of low-velocity blood flow, echo contrast between the thrombus and the surrounding flow makes it possible to clearly visualize the thrombus. SMI is a useful method to evaluate DVT, especially early after thrombus formation when it is difficult to delineate size and length because of echolucency.

Contrast‐enhanced transoral carotid ultrasonography for the evaluation of plaque protrusion after carotid artery stenting

A 67 year‐old man was admitted to our hospital because of mild left hemiparesis and was diagnosed with cerebral infarction caused by right internal carotid artery stenosis. He was treated with dual antiplatelet therapy and scheduled for carotid artery stenting 14 days after onset. The preoperative right carotid angiogram showed 60% stenosis by the NASCET criteria, with an ulcer. The postoperative angiogram suggested protrusion in the stent, which could not be seen on conventional carotid ultrasonography because of its high location. On transoral carotid ultrasonography, clear delineation of the lesion was not possible due to color blurs. Contrast‐enhanced transoral carotid ultrasonography (CETOCU) clearly demonstrated the protrusion and delineated the lumen within the stent.

Contrast-enhanced transoral carotid ultrasonography for the diagnosis and follow-up of extracranial internal carotid artery dissection: A case report

A 56‐year‐old woman was admitted to our hospital because of amaurosis fugax. The carotid angiogram showed irregularly stenotic lesions of the left and right internal carotid arteries (ICAs), suggestive of dissection. Follow‐up evaluation was performed by transoral carotid ultrasonography (TOCU) with contrast enhancement (CE), which yielded better vessel lumen and intramural hematoma visualization than color Doppler imaging. CE‐TOCU is useful for evaluating ICA dissections that extends to the high cervical portion.