Toshikazu Hirayama

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 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.

Familial amyotrophic lateral sclerosis with novel A4D SOD1 mutation with late age at onset and rapid progressive course

Our objective was to obtain clinical presentations of familial amyotrophic lateral sclerosis (FALS) with a novel Ala4Asp (A4D) SOD1 mutation in a Japanese family and to determine the epidemiological features of the SOD1 mutation on the basis of the ALS mutation database. The clinical histories and neurological findings of three affected individuals in a Japanese FALS pedigree are described. DNA analysis of SOD1 was conducted by a direct nucleotide sequence analysis. We identified a novel heterozygous A4D mutation in exon 1 in SOD1. The clinical presentations of the family were characterized by late age at onset and rapid progression. Comprehensive analysis of genotype‐phenotype correlations using the ALS mutation database revealed that all the patients with SOD1 amino acid 4 mutations tended to have a rapid progressive course of the disease with a duration of 1.27 years. The age at onset varied among SOD1 amino acid 4 mutations, but all three patients with A4D mutation had a very late age at onset of over 70 years. In conclusion, FALS patients with a novel A4D mutation in SOD1 showed a late age at onset with a rapid disease course. This study supports the previous observations that SOD1 amino acid 4 mutations contribute to the acceleration of disease progression and emphasizes the usefulness of the ALS mutation database.

Measurement of spontaneous platelet aggregation in patients with acute cerebral infarction using laser-scattered light aggregometry

【目的】従来血小板凝集は定量的な測定が困難であったため,脳梗塞急性期での詳細な検討はされていなかった.今回散乱光粒子測定装置を用いて脳梗塞急性期各病型における血小板凝集を定量的,経時的に測定した.【対象・方法】対象は脳梗塞急性期患者98例,内訳はアテローム血栓性脳梗塞(ATI)45例,ラクナ梗塞(LI)21例,心原性脳塞栓症(CE)32例であった.脳梗塞の発症日,発症後3,7,14,28日に血小板自然凝集(SPA)を測定した.【結果】脂質・糖代謝,拡張期血圧は脳梗塞後のSPAと関連があり,経過中のSPA最大値はATI群,CE群がLI群に比べ有意に高値を示した.経時的にはATI群,LI群で有意な変化がみられなかったが,CE群は発症後3日のSPAと比べ,14日で有意に低下した.【結論】脳梗塞急性期各病型によってSPAの発現に特徴がみられ,SPAは血小板活性化の指標として有用と考えられた.