Naoki Saji

New Appearance of Extraischemic Microbleeds on T2*-Weighted Magnetic Resonance Imaging 24 Hours After Tissue-type Plasminogen Activator Administration

Background and Purpose— It is unknown whether new-extraischemic microbleeds (new-EMBs) develop rapidly after tissue-type plasminogen activator (tPA) infusion. We hypothesized that new-EMBs may develop rapidly after tPA infusion using T2*-weighted MRI (T2*) and investigated the frequency and clinical factors associated with new-EMBs. Methods— Patients with acute stroke within 3 hours of onset who were treated with tissue-type plasminogen activator (tPA) were studied prospectively. T2* was performed before and 24 hours after tPA therapy. Independent clinical factors associated with new-EMBs development were examined using multivariate logistic regression analysis. Results— A total of 224 patients (121 men; mean age, 76.2±10.6 years) were enrolled in the present study. MBs before tPA infusion were observed in 72 (32.1%) patients. Within 24 hours after tPA infusion, 6 (2.7%) patients had symptomatic intracranial hemorrhage (extraischemic [n=4], and hemorrhagic transformation [n=2]). Follow-up T2* revealed asymptomatic new-EMBs in 11 (4.9%) patients and hemorrhagic transformation in the infarcted area in 65 (29.0%). The total and mean number of new-EMBs were 23 and 1.6±1.3, respectively. Patients with new-EMBs more frequently had symptomatic extraischemic hemorrhage than those without new-EMBs (27.3% [3/11] versus 0.5% [1/213]; P=0.0003). However, the frequency of hemorrhagic transformation was not different between patients with and without new-EMBs (27.3% versus 29.1%; P=0.9999). Multivariate logistic regression demonstrated that the presence of MBs before tPA infusion was the only independent factor associated with new-EMBs (odds ratio, 10.6; 95% confidence interval, 20.68–54.279; P=0.0046). Conclusions— New-EMBs occurred rapidly after tPA infusion in 4.9% of patients. The presence of MBs before tPA therapy was associated with new-EMBs. Patients with new-EMBs are likely to have symptomatic extraischemic hemorrhage.

Increased brachial-ankle pulse wave velocity is independently associated with white matter hyperintensities.

Background: White matter hyperintensities (WMHs) are a risk factor for stroke. Their etiology is considered to be cerebral microvascular abnormality. However, the association between WMHs and arteriosclerosis is not yet clear. The aim of this hospital-based cohort study was to identify the arteriosclerotic characteristics associated with WMHs. Methods: We cross-sectionally included 240 consecutive patients with no history of stroke. We measured the brachial-ankle pulse wave velocity (baPWV), ankle brachial pressure index, and intima-media thickness of the common carotid artery, and we performed magnetic resonance brain imaging. WMHs were defined as periventricular hyperintensity (Fazekas grade ≧3) and/or separate deep white matter hyperintense signals (Fazekas grade ≧2). We determined the prevalence of WMHs, silent brain infarction (SBI), hypertension, hypercholesterolemia, diabetes mellitus, ischemic heart disease, and smoking. We compared 2 groups of patients, defined by the presence or absence of WMHs, using multiple logistic regression analyses. Results: In multivariable analysis, SBI (OR 3.38; 95% CI 1.52–7.72), hypertension (OR 2.23; 95% CI 1.03–5.15), female sex (OR 1.95; 95% CI 1.03–3.76), baPWV (OR 1.12; 95% CI 1.02–1.23), and age (OR 1.09; 95% CI 1.04–1.14) were independently associated with WMHs. Conclusions: An increased baPWV is associated with WMHs. Management of increased baPWV may help to prevent the progression of WMHs and stroke.

Silent brain infarct is independently associated with arterial stiffness indicated by cardio-ankle vascular index (CAVI)

It is still unclear whether silent brain infarct (SBI) and white-matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) scans are associated with cardio-ankle vascular index (CAVI), a novel parameter of arterial stiffness. We studied 220 consecutive patients (mean age, 69 years) without a history of stroke or transient ischemic attack. Patients were assessed for the presence of SBI, WMHs and risk factors. Arterial stiffness was evaluated using CAVI. Patients were categorized into one of two groups according to the presence or absence of SBI and WMHs, and clinical characteristics were compared between the two groups. CAVI was significantly higher in patients with SBI or in patients with WMHs than in those without those respective findings. The CAVI cutoff values for detection of SBI and WMHs were 9.2 and 8.9, respectively. On multivariable analyses, CAVI, a one point increase in CAVI: odds ratio (OR), 1.25; 95% confidence interval (CI), 1.01–1.56; CAVI⩾9.2: OR, 2.34; 95% CI, 1.16–5.02, was independently associated with SBI, however, CAVI was not independently associated with WMHs. Patients with CAVI ⩾9.2 had higher OR for the presence of both SBI and WMHs (OR, 2.57; 95% CI, 1.15–5.98) when compared with patients with CAVI <9.2 after adjustment for age and sex. SBI is independently associated with arterial stiffness indicated by CAVI.

Arterial Stiffness and Progressive Neurological Deficit in Patients With Acute Deep Subcortical Infarction

Background and Purpose— The mechanism of progressive neurological deficit (PND) in patients with ischemic stroke remains unclear. The aim of this study was to clarify whether arterial stiffness, a marker of vascular endothelial impairment and arteriosclerosis, is associated with PND in patients with acute deep subcortical infarction. Methods— We evaluated 156 consecutive first-ever ischemic stroke patients with acute deep subcortical infarction. PND was defined as an increment of ≥2 points in the National Institute of Health Stroke Scale score or an increase of ≥1 point in the limb weakness score within 7 days of stroke onset. Patients were assessed for risk factors, and infarct size was measured on initial diffusion-weighted magnetic resonance imaging. We measured brachial-ankle pulse wave velocity (baPWV) as a marker of arterial stiffness. We divided patients into 2 groups according to the presence or absence of PND to compare their clinical characteristics. Results— Fifty-two patients (33%) had PND, and baPWV was significantly higher in patients with than in those without PND. The baPWV cut-off value for PND was 18.24 m/s, with 90% sensitivity and 47% specificity. In multivariable logistic regression analysis, high baPWV (≥18.24 m/s; odds ratio, 8.22; 95% confidence interval, 2.55–31.9), large infarct size (≥15 mm; odds ratio, 2.76; 95% confidence interval, 1.01–7.92), and ≥3 infarct slices on serial axial diffusion-weighted imaging (odds ratio, 3.38; 95% confidence interval, 1.22–10.0) were independently associated with PND. Conclusions— Arterial stiffness indicated by baPWV is independently associated with PND in patients with acute deep subcortical infarction.

Comparison of arteriosclerotic indicators in patients with ischemic stroke: ankle-brachial index, brachial-ankle pulse wave velocity and cardio-ankle vascular index.

The ankle–brachial index (ABI), brachial–ankle pulse wave velocity (baPWV) and cardio–ankle vascular index (CAVI) are surrogate markers of arteriosclerosis. However, their roles in patients with acute ischemic stroke remain unclear. From October 2003 to September 2011, we enrolled patients with arteriosclerotic ischemic stroke (AIS) exhibiting large infarcts attributed to large-artery atherosclerosis (LAA) or deep subcortical infarcts (mainly lacunar infarcts) attributed to small-artery disease (SAD). Outpatients without a history of stroke served as controls (CTL). We divided the study period into two terms and assessed patients using two different oscillometric devices (Form PWV/ABI, Omron Colin; and VaSera VS-1500, Fukuda Denshi) in each term. One-way analysis of variance and age- and sex-adjusted analysis of covariance were used to compare the three groups. We analyzed 842 patients. The ABI was significantly lower in the LAA (n=102) group than in the SAD (n=280) and CTL (n=460) groups. The baPWV was significantly higher in the LAA and SAD groups than in the CTL group. The CAVI gradually increased in the order of CTL, SAD and LAA. The cutoff values of baPWV and CAVI for detection of AIS were 18.3 m s−1 (odds ratio (OR): 6.09, 95% confidence interval (CI): 3.97–9.62, P<0.01) and 9.5 (OR: 1.44, 95% CI: 1.24–1.70, P<0.001), respectively. Among the three indicators, a lower ABI indicated advanced atherosclerosis associated with LAA, and an increased baPWV more closely indicated AIS. An increased CAVI may indicate the degree of vessel stiffness due to arteriosclerosis.

Elevated glucose level adversely affects infarct volume growth and neurological deterioration in non-diabetic stroke patients, but not diabetic stroke patients.

Hyperglycemia is recognized as a common occurrence associated with a high risk of poor outcome in ischaemic stroke patients. However, little is known about the association between elevated glucose level, growth of infarct volume and neurological deterioration in ischaemic stroke patients without diabetes. The present study aimed to clarify this issue in acute ischaemic stroke patients with arterial occlusion.

Early initiation of new oral anticoagulants in acute stroke and TIA patients with nonvalvular atrial fibrillation

BACKGROUND AND PURPOSE The aim of this study was to investigate whether early initiation of new oral anticoagulants (NOAC) for acute stroke or transient ischemic attack (TIA) patients with nonvalvular atrial fibrillation (NVAF) are safe. METHODS Between March 2011 and September 2012, stroke or TIA patients with NVAF who started NOAC within 2 weeks were enrolled retrospectively. Symptomatic intracerebral hemorrhage (ICH), hemorrhagic transformation (HT) on T2*-weighted MRI, recurrence of stroke or TIA, systemic embolism and any bleeding complications after initiation of NOAC were evaluated. RESULTS 41 patients (25 males; mean age 76.2 years) started NOAC; of which, 39 (95%) patients had stroke, and 2 (5%) had TIA. The median (interquartile range) interval from onset to treatment with NOAC was 2 (1-6) days. Symptomatic ICH was not observed. HT on initial T2* and new HT on follow-up T2* were 5 (12%) and 11 (31%), but it was asymptomatic. Of 5 patients who had HT on the initial T2*, enlargement of hemorrhage on follow-up T2* (hemorrhagic infarction (HI) Type 1→HI Type 2) was observed in 1 patient, but it was asymptomatic. None of the patients had recurrent stroke or TIA, systemic embolism, and any bleeding complications. CONCLUSIONS The NOAC may be safe in acute stroke or TIA patients with NVAF. A large, prospective study is needed to confirm this.

Intracranial Hemorrhage Caused by Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) – Multicenter Retrospective Cohort Study in Japan –

BACKGROUND We conducted a multicenter retrospective cohort study to elucidate the characteristics of intracranial hemorrhage (ICH) in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants (NOACs). METHOD AND RESULTS We sent a questionnaire to the directors of 241 stroke centers in Japan to establish the clinical characteristics of NOAC-associated cerebral hemorrhage (CH), including hematoma size, hematoma enlargement (HE) and in-hospital mortality of patients treated in their institutions. We undertook a literature review to establish the clinical characteristics of warfarin-associated CH and compared these with our data. We received 174 responses (72.2%), of which 67 (38.5%) gave anonymous details of 130 eligible patients (male, 67.7%; mean age, 77.3±8.3 years, in-hospital mortality rate, 11.5%). We judged that 87 of the 130 patients had presented with CH: one-fifth had taken antiplatelet drugs. We found that the incidences of HE and mortality in the 87 patients presenting with NOAC-associated CH were lower than would have been expected in those with warfarin-associated CH (17% vs. 26%, and 16% vs. 35%, respectively). CONCLUSIONS More than half the stroke center directors who responded to our questionnaire had not experienced cases of NOAC-associated ICH. Compared with warfarin, NOACs appear to present a lower risk of HE and death in patients with atrial fibrillation who develop CH.

Functional independence measure scores predict level of long-term care required by patients after stroke: a multicenter retrospective cohort study

Abstract Purpose: To examine whether Functional Independence Measure (FIM) scores on admission can predict the future care levels of patients after acute stroke. Methods: In this multicenter retrospective cohort study, we enrolled post-acute stroke patients and assessed stroke subtypes, self-care abilities using FIM scores, and discharge destination. Patients’ care levels were assessed according to the Long-Term Care Insurance (LTCI) system (0–5: slight impairment to bedridden), the national insurance plan for care in Japan, at discharge. We divided patients into two groups according to LTCI care levels (0–2 versus 3–5) to compare their clinical characteristics using multivariate logistic regression analysis. The trial was registered with the UMIN Clinical Trials Registry (UMIN000012653). Results: Of the 1261 patients (47% female, mean age 75 years), 492 (39%) fulfilled LTCI care levels 0–2. FIM scores on admission were significantly correlated with LTCI care levels (p < 0.001). On multivariate analysis, age and FIM scores on admission were found to be independent predictors of LTCI care levels 0–2. Conclusions: FIM scores on admission after stroke can independently predict later care requirements. Early prediction of LTCI care levels may contribute to the early supported discharge and improve the efficiency of healthcare planning. Implications for Rehabilitation There is a clear relationship between Functional Independence Measure (FIM) scores and the care levels certified by the Long-Term Care Insurance (LTCI) system, a national healthcare and insurance system in Japan. FIM scores on admission can predict future LTCI care levels required for patients after acute stroke. Early prediction of LTCI care levels may contribute to early supported discharge, improve the efficiency of stroke management and assist healthcare planning.

The DASH score: a simple score to assess risk for development of malignant middle cerebral artery infarction.

BACKGROUND AND PURPOSE The aim of the present study was to devise a simple grading scale for assessing the risk of development of malignant MCA infarction (MMI). METHODS Using MRI, patients with MCA infarction and proximal vessel occlusion (ICA or M1) within 24h of onset were retrospectively studied. MMI was defined as clinical deterioration, midline shift ≥ 5 mm, or brain herniation within 48 h of admission. We evaluated clinical factors independently associated with MMI and created a simple score according to the multivariate logistic regression analysis. RESULTS Subjects comprised 119 patients, 57 of which (47.9%) developed MMI. Multivariate logistic regression analysis revealed the following independent factors associated with MMI: DWI ASPECTS ≤ 3 [odds ratio (OR), 4.16; 95% CI, 1.36-12.66, P=0.012], ACA territory involvement [OR, 6.90; 95% confidence interval [CI], 2.06-23.10, P=0.002], M1 susceptibility vessel sign (SVS) on T2*-gradient echo [OR, 4.55; 95% CI, 1.38-14.98, P=0.013], and hyperglycemia (glucose value ≥ 145 mg/dl) [OR, 5.31; 95% CI, 1.80-15.68, P=0.002]. These four variables were selected for use in the DASH score, with DWI ASPECTS ≤ 3 as 1 point, ACA territory involvement as 1 point, M1 SVS as 1 point, and hyperglycemia as 1 point. The likelihood of developing MMI for each score was as follows: score 0, 9.1%; score 1, 20.5%; score 2, 63.0%; score 3-4, 96.8%. The C statistic for the score was 0.88 (95% CI, 0.82-0.94, P<0.001). CONCLUSION Our DASH score reliably assessed a risk for development of MMI in large MCA infarctions.