Satoshi Takaishi

Effects of Edaravone, a Free Radical Scavenger, on Serum Levels of Inflammatory Biomarkers in Acute Brain Infarction

The potent free radical scavenger edavarone is widely used in Japan to treat acute ischemic stroke within 24 hours after onset. Recent experimental studies have shown that edavarone alleviates blood-brain barrier disruption in conjunction with suppression of the inflammatory reaction in acute brain ischemia. We investigated the effects of edaravone on circulating inflammatory biomarkers in patients with ischemic stroke. Patients with acute ischemic stroke admitted 12-36 hours after onset of symptoms were prospectively enrolled. Intravenous edaravone at 60 mg/day for 14 days was administered to patients admitted 12-24 hours after symptom onset (edaravone group; n = 29). Patients admitted 24-36 hours after onset served as controls (control group; n = 34). Venous blood samples were obtained on admission and at 48 hours, 7 days, and 14 days after symptom onset. Serum concentrations of high-sensitivity C-reactive protein, interleukin (IL)-6, IL-10, IL-18, tumor necrosis factor α, matrix metalloproteinase (MMP)-2, and MMP-9 were measured. General linear models were used to compare changes in concentrations of these biomarkers over time between the groups. In the control group, the mean MMP-9 concentration increased gradually from 3.857 ± 1.880 ng/mL to 4.538 ± 1.966 ng/mL over the 14-day period (P = .027, one-way repeated-measures analysis of variance [ANOVA]), but the edavarone group demonstrated no such increase (P = .564). A significant group-time interaction was demonstrated only for MMP-9 (P = .029, two-way repeated-measures ANOVA), and no significant differences in other biomarkers were seen between groups. Our data indicate that edaravone suppresses serum MMP-9 level in patients with acute ischemic stroke. Further studies with a larger sample size are needed to explore the relationship between circulating MMP-9 level and the protective effect of edaravone.

Association between Inflammatory Biomarkers and Progression of Intracranial Large Artery Stenosis after Ischemic Stroke

BACKGROUND Proinflammatory state has been implicated as a pathogenetic mechanism in the progression of intracranial large artery atherosclerosis (ILA). High levels of inflammatory biomarkers in healthy populations and in patients with acute stroke or acute coronary syndrome are known to be associated with subsequent stroke events. This study investigated the relationship between circulating biomarkers measured early after stroke onset and future ILA progression. METHODS In 48 patients with acute ischemic stroke, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), IL-18, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2 and MMP-9 were measured within 48 hours after onset. Baseline severity and ILA progression were assessed by serial magnetic resonance angiography (MRA). The median follow-up period for MRA was 3.1 years. Hazard ratio (HR) was calculated using the Cox proportional hazard model adjusted for traditional risk factors, and accuracy of predicted ILA progression was analyzed by receiver operating characteristic (ROC) curve analysis. RESULTS ILA progression was observed in 6 of 48 patients (12.5%). After adjusting for age, sex, and presence of hypertension, baseline ILA severity score (HR 2.814; 95% confidence interval [CI] 1.172-6.754) and IL-6 (HR 1.215; 95% CI 1.002-1.473) were significantly associated with ILA progression. Area under the ROC curve (AUC) for prediction of ILA progression by traditional risks, baseline ILA severity score and IL-6, was 0.647. When IL-6 was removed from this model, AUC remained at 0.631. CONCLUSIONS In addition to traditional risk factors and baseline radiologic findings, circulating levels of IL-6 measured soon after stroke onset are associated with future ILA progression.

Association between paroxysmal atrial fibrillation and the left atrial appendage ejection fraction during sinus rhythm in the acute stage of stroke: a transesophageal echocardiographic study.

BACKGROUND This study aimed to investigate whether left atrial appendage (LAA) dysfunction evaluated by transesophageal echocardiography (TEE) during sinus rhythm is predictable of paroxysmal atrial fibrillation (PAF) as an embolic source in the acute stage of stroke. METHODS AND RESULTS We measured and analyzed LAA flow velocity (LAA-FV) and LAA ejection fraction (LAA-EF) in 300 acute ischemic stroke patients by TEE. We divided the acute ischemic stroke patients into 3 groups. The atrial fibrillation (AF) group (n=58) comprised patients whose TEE was performed during AF rhythm. The PAF group (n=42) comprised patients with a history of AF but with normal sinus rhythm when TEE was performed. The normal sinus (sinus) group (n=200) did not have any history of AF. We found that mean LAA-FV and LAA-EF values in the PAF group were significantly lower than those in the sinus group (P<.001). The diagnostic accuracy of LAA-FV for the diagnosis of PAF calculated as the area under receiver operating characteristic curves was low (.582, 95% confidence interval [CI]=.498-.665) but that of LAA-EF was modest (.721, 95% CI=.653-.789), with an optimal cutoff point of 49.1%. CONCLUSIONS LAA dysfunction as determined by TEE (LAA-EF<49.1%) in the acute stage of stroke is predictive of PAF with moderate accuracy. Long-term electrocardiographic monitoring is recommended for cryptogenic stroke patients with LAA dysfunction.

Effects of Pretreatment Cerebral Blood Volume and Time to Recanalization on Clinical Outcomes in Endovascular Thrombectomy for Acute Ischemic Stroke

BACKGROUND Faster time to recanalization leads to better clinical outcomes in patients treated with endovascular thrombectomy. Whether the association between time to recanalization and clinical outcomes depends on cerebral blood volume (CBV) obtained from pretreatment computed tomography (CT) perfusion (CTP) imaging was investigated. METHODS In consecutive patients with acute ischemic stroke who achieved recanalization by endovascular thrombectomy for intracranial internal carotid artery or M1 occlusion, the effects on clinical outcome of time to recanalization and the relative CBV value (rCBV) assessed by pretreatment CTP were evaluated. The patient population was divided into 2 groups according to rCBV: normal rCBV group (rCBV ≥ .9) and low rCBV group (rCBV < .9). In each group, time to recanalization was compared between the good and the poor clinical outcome groups. RESULTS Sixty-four patients were eligible for this study. Twenty-six patients (40.6%) achieved good clinical outcomes. In the normal rCBV group, no association was found between clinical outcome and time to recanalization. In the low rCBV group, time to recanalization from CTP (101 minutes versus 136 minutes, P = .040) was significantly shorter in the good clinical outcome group. On binary logistic regression modeling, CTP to recanalization time (odds ratio 1.035 [1.004-1.067], P = .025) was an independent predictor of good clinical outcome only in the low rCBV group. CONCLUSIONS The association between time to recanalization and clinical outcomes depends on rCBV obtained from pretreatment CTP. Time to recanalization is more important for good clinical outcomes in patients with low rCBV than in patients with normal rCBV.

Abstract TP10: Endovascular Treatment for Acute Ischemic Stroke With Intracranial Atherosclerotic Occlusive Disease

Background: Treatment strategy for acute ischemic stroke with intracranial atherosclerotic disease remains unknown. The aims are to evaluate whether revascularization rates, procedural complication...

Long-Term Outcome of Balloon Angioplasty Without Stenting for Symptomatic Middle Cerebral Artery Stenosis

PURPOSE A recent randomized controlled trial demonstrated that aggressive medical management was superior to angioplasty with stenting for intracranial stenosis. The purpose of this study was to assess initial and long-term outcomes of balloon angioplasty without stenting for symptomatic middle cerebral artery (MCA) stenosis. METHODS We retrospectively analyzed the clinical data of 72 patients (mean age, 58.9 years old) with 84 balloon angioplasties without stenting for high-grade (>70%) atherosclerotic stenosis of the main trunk of the MCA. All patients had experienced recurrent transient ischemic attack or minor stroke resistant to medical treatment. We assessed perioperative and long-term outcomes such as restenosis and the recurrence of strokes. The follow-up period was a median of 63 months (range, 6-171 months). RESULTS Balloon angioplasty was successful in 97% of procedures. During the 30-day perioperative period, a total of 3 patients suffered from stroke (4.2%) without death. A total of 23 (31.9%) patients had restenosis at a time point that varied from 6 to 111 months. Diabetes mellitus (DM) was noted significantly more often in the restenosis group (39%) than in the nonrestenosis group (13%). Multivariate logistic regression analysis revealed DM (odds ratio, 4.84; 95% confidence interval, 1.196-19.62; P = .027) as an independent predictor of restenosis. Restenosis and DM were indicated as independent predictors of the recurrence of ischemic stroke and transient ischemic attack. CONCLUSIONS Balloon angioplasty without stenting for symptomatic MCA stenosis can be performed with a high successful rate and a low risk of complications. Long-term outcome data suggest that this procedure reduces the risk of further strokes.