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Treatment with alteplase for acute ischemic stroke patients with an unknown time of onset is safe and effective. However, clinical trials have some selection bias. The purpose of this study was to clarify the efficacy and safety of alteplase treatment in patients with unknown time of onset in a real-world clinical setting.We included consecutive patients with acute ischemic stroke visited within 4.5 h of onset or symptom recognition. We divided patients into two groups: onset clear group (C-group) and unknown time of onset group (U-group). We treated patients with an unknown time of onset if the DWI-FLAIR mismatch was positive. We calculated the prevalence of alteplase treatment in each group and compared prognosis between the two groups.Six hundred thirty-two patients arrived within 4.5 h of onset or symptom recognition. Of these, 446 patients (71 %) were in the C-group and 186 (29 %) in the U group. Alteplase treatment was performed in 35 % of patients in the C group and in 18 % in the U group (p 0.001). Favorable outcomes at 90 days in patients treated with alteplase were comparable between the C group (52 %) and the U group (53 %) (p = 0.887). All hemorrhagic complications, including non-symptomatic hemorrhagic transformation, occurred in 11 of 157 patients (7 %) in the C-group and one of 34 patients (3 %) in the U-group (p = 0.696).In a real-world clinical setting, alteplase treatment was performed safe in 18% of patients with an unknown time of stroke onset based on patient selection using the DWI-FLAIR mismatch.

Objective Left ventricular (LV) thrombus is a rare condition in acute cerebral infarction. The prevalence and features of cerebral infarction with LV thrombus are unclear. We explored the features of cerebral infarction due to LV thrombus. Methods In this single-center retrospective study, we investigated consecutive patients with acute ischemic stroke admitted within seven days of the onset who had LV thrombus found by transthoracic echocardiography (TTE). First, we calculated the prevalence of LV thrombus in patients with cardioembolic stroke (CES). Second, we investigated the baseline characteristics, including the TTE findings and features of cerebral infarction due to LV thrombus. Results From June 2012 to January 2019, a total of 5,693 patients were enrolled. Of these, 1,408 (25%) patients were diagnosed with CES. Of these 1,408 patients with CES, 13 (0.9%) had LV thrombus indicated by TTE, with dilative cardiomyopathy, subacute myocardial infarction, and old myocardial infarction present in 1 (8%), 2 (15%), and 10 (77%), respectively. The ejection fraction (EF) was 48.9% (25.3-64.7%). The maximum longitudinal size of LV thrombus was 13.4 (0.97-38.1) mm, and there was no correlation between the size of the LV thrombus and the EF. Regarding the features of cerebrovascular infarction, major vessel occlusion was observed in 10 (77%) patients. Six (46%) patients were found to have good outcomes (modified Rankin Scale 0-2) at 90 days after the onset. Conclusion LV thrombus was seen in 0.9% of patients with CES. Many of the patients with LV thrombus had major vessel occlusion.

Although the assessment of nutrition is essential for stroke patients, detailed associations between nutritional status at admission, subsequent complications, and clinical outcomes in patients with acute intracerebral hemorrhage (ICH) are unclear. We aimed to elucidate these associations using the Controlling Nutritional Status (CONUT) score. Consecutive patients with acute ICH were investigated. Nutritional status was evaluated using the CONUT score, calculated from the serum albumin level, lymphocyte count, and total cholesterol level. Subsequent complications, such as hemorrhage expansion (HE) during the acute stage and aspiration pneumonia during hospitalization, were evaluated. Poor outcome was defined as a modified Rankin Scale score of ≥ 3 at 3 months. Of the 721 patients, 49 had HE, 111 had aspiration pneumonia, and 409 had poor outcomes. Patients with HE had significantly lower total cholesterol levels than those without HE. Patients with aspiration pneumonia had significantly lower albumin levels, lower lymphocyte counts, and higher CONUT scores than those without aspiration pneumonia. Patients with poor outcomes had significantly lower albumin levels, lower lymphocyte counts, lower total cholesterol levels, and higher CONUT scores than those with good outcomes. Multivariable logistic analysis showed that higher CONUT scores were independently associated with poor outcome (odds ratio, 1.28; 95% confidence interval, 1.09-1.49; P = 0.002) after adjusting for baseline characteristics, HE, and aspiration pneumonia. Each component of CONUT was a useful predictor of subsequent complications. Malnutrition, determined using the CONUT score, was independently associated with poor outcomes in patients with ICH after adjusting for these complications.

Objective The Suita score is used to predict the 10-year prognosis of developing coronary heart disease (CHD). This study examined the association between the Suita score and stroke recurrence within one year in Japanese patients who experienced first-ever ischemic stroke. Methods This prospective cohort study at a stroke center in Japan included patients who experienced first-ever acute ischemic stroke (AIS) or a transient ischemic attack (TIA). During hospitalization, the Suita score was measured as the main exposure. Patients with a ≥5% predicted CHD risk were classified into the high-risk group. The primary outcome was stroke recurrence within one year of the stroke onset. A multivariate Cox regression analysis was conducted and adjusted for confounding and prognostic factors. Results Among the 1,204 patients evaluated, 937 (78%) were classified as having a high risk of developing CHD. Stroke recurrence was observed in 66 patients during the follow-up period. In the multivariate analysis, after adjusting for confounding and prognostic factors, such as non-small vessel occlusion and prescription of lipid-lowering agents at the time of discharge, a ≥5% predicted CHD risk was associated with the 1-year stroke recurrence after the initial onset [adjusted hazard ratio (HR) =2.20, 95% confidence interval (CI) =1.00-4.91, p=0.049; adjusted HR=2.00, 95% CI=1.01-4.14, p=0.048; adjusted HR=0.42, 95% CI=0.24-0.73, p=0.002]. Conclusion The Suita score, adapted for use in ischemic stroke with the same mechanism, correlated with the short-term recurrence within one year. Our findings suggest that the Suita score may be useful for predicting the long-term prognosis of developing CHD as well as the short-term recurrence for patients with first-ever AIS and TIA.

Aim This study aimed to investigate the diagnostic yield of 7-day Holter monitoring for detecting covert atrial fibrillation (AF) in patients with recent embolic stroke of undetermined source (ESUS) and to identify the pre-entry screening biomarkers that had significant associations with later detection of AF (clinicaltrials.gov. NCT02801708). Methods A total of 206 patients who have recent ESUS without previously documented AF underwent Holter electrocardiography using a chest strap-style monitor. External validation of biomarkers predictive of AF was performed using 83 patients with ESUS who were implanted with insertable cardiac monitors. Results The 7-day Holter monitoring started at a median of 13 days after the onset of stroke. AF was detected in 14 patients, and three of these showed a single AF episode lasting ＜2 min. The median time delay to the first documented AF was 50 h. Each of serum brain natriuretic peptide ≥ 66.0 pg/mL (adjusted odds ratio 5.23), atrial premature contractions (APCs) ≥ 345 beats (3.80), and APC short runs ≥ 13 (5.74) on 24-h Holter prior to the 7-day Holter showed a significant association with detection of AF, independent of age and physiological findings in this derivation cohort, and all of these showed a significant association in the validation cohort (adjusted odds ratio 6.59, 7.87, and 6.16, respectively). Conclusions In recent ESUS patients, the detection rate of AF using the 7-day Holter monitoring was 6.8% (95% CI 4.1%-11.1%). Brain natriuretic peptide, APC count, and APC short runs in the standard clinical workup seemed to be predictors of covert AF.

Introduction and Objectives: The clinical characteristics of convexity subarachnoid hemorrhage (cSAH) accompanying hyperacute ischemic stroke are unknown. We aimed to investigate the incidence and clinical characteristics of cSAH with hyperacute ischemic stroke. Methods: Participants comprised symptomatic ischemic stroke patients with ≤4.5 h from onset to door who also underwent initial MRI ≤4.5 h from onset. We reviewed initial and follow-up MRI during admission to identify cSAH. Retrospective reviews of cSAH incidence and clinical characteristics were performed. Results: We screened 1,249 consecutive symptomatic ischemic stroke patients, including 384 patients (279 males [73%]; median age, 67 years). Of the 384 patients, arterial ischemic stroke was seen in 382 patients, and venous ischemic stroke in 2 patients. Of the hyperacute arterial ischemic stroke, cSAH was identified within 4.5 h of ischemic stroke onset in 2 patients (0.5%) and around 6 days from ischemic stroke onset in 2 patients (0.5%). Of the hyperacute venous ischemic stroke, cSAH was observed in 1 patient on initial MRI. Comparing the clinical characteristics of hyperacute arterial ischemic stroke with and without cSAH, patients with cSAH were more likely to have arterial stenosis or occlusion ipsilateral to the cSAH (100 vs. 47%, p = 0.048), and the ischemic lesion only in the right hemisphere (100 vs. 33%, p = 0.013). In all cases, outcomes were favorable (modified Rankin Scale 0–1 at 3 months from onset). Conclusions: Convexity SAH was observed in 0.5% of hyperacute ischemic patients within 4.5 h of ischemic stroke onset and in 0.5% around 6 days from ischemic stroke onset.

To determine transcranial Doppler ultrasonography (TCD) parameters related to unfavorable outcomes, and to clarify the correlations between those parameters and heart functions in acute ischemic stroke without major vessel stenoses and occlusions.Patients were selected from a comprehensive stroke center between October 2012 and June 2019. Inclusion criteria were: 1) acute ischemic stroke without major vessel stenoses and occlusions; and 2) ability to measure blood flow in the middle cerebral artery by TCD. Unfavorable outcomes were defined as a modified Rankin Scale score of 2-6 at 3 months after onset. First, we investigated TCD parameters related to unfavorable outcomes. Second, correlations between those parameters and heart functions as assessed by transthoracic echocardiography were evaluated.We screened 1,527 consecutive ischemic stroke patients, including 130 patients (109 [83%] male; median age, 60 years). Middle cerebral artery pulsatility index (M1 PI) (Odds ratio (OR) 0.057, 95%confidence interval (CI) 0.007-0.494, p = 0.009) was independently associated with unfavorable outcomes. Concerning the relation between M1 PI and heart functions, peak early filling velocity/velocity of mitral annulus early diastolic motion (E/e') (OR 1.195, 95%CI 1.011-1.413, p = 0.037) was a factor independently associated with high M1 PI.High M1 PI predicts unfavorable outcome regardless of ischemic stroke subtype without major vessel stenoses and occlusions. High M1 PI correlates with high E/e', suggesting diastolic dysfunction.

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 p0.05), between IS/TIA and ICH among both NOAC and VKA users. Cerebral microbleeds (CMBs) [odds ratio (OR), 4.77; p0.0001] 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; p0.0001) 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.

Objectives To investigate the differences in clinical backgrounds, especially weekly variations of stroke occurrence, between hyper-acute ischemic stroke patients with and without regular employment (RE), as well as the impact of RE on outcome. Materials and methods Symptomatic ischemic stroke patients with ≤4.5 h from onset to door were enrolled. First, we divided patients into the RE and non-RE group to analyze differences in clinical characteristics, especially relation between weekly variations of stroke occurrence and RE. Second, we divided the same patients into those with and without favorable outcomes (modified Rankin Scale score of 0 to 2 at 3 months from stroke onset) to analyze the impact of RE on outcomes. Results We screened 1,249 consecutive symptomatic ischemic stroke patients and included 377 patients (284 [75%] males; median age, 67 years). Of these patients, 248 (66%) were included in RE group. First, RE was independently associated with occurrence of stroke on Monday in reference to Sunday or a public holiday (OR 2.562, 95% CI 1.004-6.535, p = 0.049). Second, RE (OR 2.888 95% CI 1.378-6.050, p = 0.005) was a factor independently associated with a favorable outcome. Conclusions Patients with RE were more likely to have a hyper-acute ischemic stroke on Monday in reference to Sunday or a public holiday. However, RE before stroke onset appears to have a positive impact on outcome.

Prescribing under-dose direct oral anticoagulants (DOACs) for non-valvular atrial fibrillation (NVAF) is alerted to increase cardiovascular events or death. However, the association between dose selection of DOACs and the clinical course remains unclear. This study aimed to propose a novel criterion for selecting the DOAC dose and investigate clinical characteristics of ischemic stroke (IS) under this criterion.We assessed the pooled prospective multicenter registry data of stroke patients taking anticoagulant agents, including IS patients with NVAF and prior DOAC usage. The recommended dose according to the reduction criteria of each DOAC and the selected dose were identified for each patient, and patients were categorized into four groups: no alternative low-dose, selecting low-dose appropriately with all DOACs applicable for reduction criteria; selected low-dose, selecting low-dose appropriately or inappropriately despite at least one DOAC inapplicable for reduction criteria; selected standard-dose, appropriate standard-dose use; and absolute over-dose, inappropriate standard-dose regardless of criteria. We investigated the effects of dose selection of DOACs on short-term poor functional outcomes.322 patients were included in the analysis. The prevalence of no alternative low-dose, selected low-dose, selected standard-dose, and absolute over-dose was 74 (23%), 144 (45%), 89 (27%), and 15 (5%), respectively. Multivariable analysis found that the selected low-dose group showed significantly poorer functional outcomes than the selected standard-dose group only in patients without renal dysfunction (OR, 2.60; 95% CI, 1.17-6.00; P = 0.0186).Selecting a low dose DOAC might be associated with poor functional outcomes in patients without renal dysfunction.

An 81-year-old woman presented to our emergency room by ambulance with gait disturbance and pain in her left neck. Magnetic resonance imaging (MRI) showed acute left-sided dorsolateral medullary infarction and an occluded left vertebral artery. The temporal bone echo window was insufficient, but our pastable soft ultrasound probe attached to the cervix (PSUP) detected many microembolic signals caused by the contrast agent (cMES) in the common carotid artery. Chest CT revealed right pulmonary arteriovenous fistula (PAVF) and she underwent coil embolization for PAVF considering the possibility of paradoxical embolism via PAVF. After embolization, the cMES disappeared on PSUP. Therefore, PSUP was useful for diagnosing and confirming the interventional procedural success for performing PAVF.

Reversible cerebral vasoconstriction syndromes (RCVS) have been well recognized recently as one cause of cerebrovascular disease, but the time course of vessel vasoconstriction remains uncertain. We report herein 2 cases with RCVS in which we clarified temporal changes in vessel vasoconstriction in detail using transcranial color-coded sonography (TCCS). The first case involved a 27-year-old woman who developed intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) after severe headache. TCCS showed peak systolic velocity (PSV) in the left middle cerebral artery (MCA) peaked at 212 cm/s on day 6 and gradually decreased, whereas PSV of the left posterior cerebral artery (PCA) and left anterior cerebral artery (ACA) re-elevated to 190 cm/s on day 15. The second case involved a 53-year-old woman who developed cerebral infarction in the PCA territory 9 days after severe headache. TCCS study showed PSV elevation in the right MCA. Although TCCS seemed to normalize 7 days after admission, PSV of the left PCA, left ACA, and left MCA re-elevated at day 17. Both cases showed bimodal PSV peaks, with the posterior circulation peak preceded by the anterior circulation peak. These findings may be important in clarifying the mechanisms underlying vasoconstriction in patients with RCVS.

We report the case of a 74-year-old woman with treatment-naive chronic inflammatory demyelinating polyneuropathy evaluated by both nerve conduction studies and nerve ultrasound (NUS) before and after initial treatment. Performing both nerve conduction study and NUS before and after initial treatment seems rare for treatment-naive chronic inflammatory demyelinating polyneuropathy. This case yielded two major findings. First, improvement of nerve swelling as evaluated by NUS correlated well with the improvement of neurological symptoms. Second, NUS improvements were seen right after treatment, whereas electrophysiological improvements were not. Nerve ultrasound might thus allow for judgment of curative effects much more immediately and sensitively than nerve conduction study in treatment-naive chronic inflammatory demyelinating polyneuropathy.

Background and Purpose— We investigated whether administration of edaravone, a free radical scavenger, before or during tissue-type plasminogen activator (tPA) can enhance early recanalization in a major arterial occlusion. Methods— The YAMATO study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy) is an investigator-initiated, multicenter (17 hospitals in Japan), prospective, randomized, and open-label study. Patients with stroke secondary to occlusion of the M1 or M2 portion of the middle cerebral artery and within 4.5 hours of the onset were studied. The subjects were randomly allocated to the early group (intravenous edaravone [30 mg] was started before or during tPA) and the late group (edaravone was started after tPA and the assessment of early recanalization). Results— One-hundred sixty-five patients (96 men; median age [interquartile range], of 78 [69–85] years) were randomized 1:1 to either the early group (82 patients) or the late group (83 patients). Primary outcome, defined as an early recanalization 1.5 hour after tPA, was observed in 53% of the early group and in 53% of the late group ( P =1.000). About secondary outcomes, the rate of significant recanalization of ≥50% was not different between the 2 groups (28% versus 34%; P =0.393). The symptomatic intracerebral hemorrhage has occurred in 4 patients (5%) in the early group and in 2 patients (2%) in the late group ( P =0.443). The favorable outcome (modified Rankin Scale score of 0–2) at 3 months was also similar between the groups (53% versus 57%; P =0.738). Conclusions— The timing of edaravone infusion does not affect the rate of early recanalization, symptomatic intracerebral hemorrhage, or favorable outcome after tPA therapy. Clinical Trial Registration— URL: http://www.umin.ac.jp/ctr/index-j.htm . Unique identifier: UMIN000006330.

Purpose: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare neurodegenerative disorder with various clinical presentations. Mutation of the colony-stimulating factor 1 receptor (CSF1R) gene is considered to be a cause of this autosomal dominant disorder. The purpose of this study was to report magnetic resonance spectroscopy (MRS) findings in patients with HDLS and asymptomatic carriers and to clarify the use of MRS in this disease. Materials and Methods: In this retrospective, institutional review board-approved study, we included four consecutive patients, genetically diagnosed with HDLS, and two asymptomatic carriers after acquiring informed consent. We performed single-voxel MRS of the left centrum semiovale on a 3T clinical scanner. We also included a sex-matched normal dataset. We quantified N-acetylaspartate (NAA), creatine, choline-containing compounds (Cho), glutamine, glutamate (Glu), myo-inositol (Ins), glutathione, lactate (Lac), and gamma-amino butyric acid using LCModel. We performed statistical analysis, and P value

Background The aim of the present study was to investigate the efficacy and safety of antiplatelet (aspirin plus cilostazol) dual therapy for patients with noncardioembolic stroke within 48 hours of symptom onset. Methods and Results The ADS (Acute Aspirin Plus Cilostazol Dual Therapy for Non‐Cardiogenic Stroke Patients Within 48 Hours of Symptom Onset ) study is an investigator‐initiated, prospective, multicenter (34 hospitals in Japan), randomized, open‐label, and aspirin‐controlled trial. Acute stroke patients with noncardioembolic stroke within 48 hours of onset were studied. The subjects were randomly allocated to combination therapy with aspirin 81 to 200 mg plus cilostazol 200 mg (dual group) and single therapy with aspirin 81 to 200 mg (aspirin group) for 14 days. After the 14 days, all patients took the cilostazol 200 mg for 3 months. A primary efficacy outcome was defined as any one of the following occurring (neurological deterioration, symptomatic stroke recurrence, or transient ischemic attack) within 14 days. A primary safety outcome included intracerebral hemorrhage and subarachnoid hemorrhage. Between May 2011 and June 2017, 1201 patients (796 [66%] men; median age, 69 [61–77] years) randomized 1:1 to either the dual group or the aspirin group were analyzed. Initial National Institutes of Health Stroke Scale score was 2 (1–4) in both groups ( P =0.830). A primary efficacy outcome was observed in 11% in the dual group and 11% in the aspirin group ( P =0.853). A primary safety outcome occurred in 2 (0.3%) in the dual group and in 1 (0.2%) in the aspirin group ( P =0.624). Conclusions Dual antiplatelet therapy using cilostazol and aspirin was safe but did not reduce the rate of short‐term neurological worsening. Clinical Trial Registration URL : umin.ac.jp/ctr/index/htm. Unique identifier: UMIN 000004950.

The precise mechanisms underlying the expansion of lacunar and giant lacunar infarction remain unclear. We aimed to determine risk factors for lacunar and giant lacunar infarction and to clarify differences in pathophysiological mechanisms for these two groups.Patients were selected from a comprehensive stroke center with ≤24 h from onset to initial magnetic resonance imaging with lacunar and giant lacunar infarction. All patients underwent a second magnetic resonance imaging during hospitalization. Infarct size was calculated and compared by the positive region on diffusion-weighted imaging. Factors related to infarct expansion were evaluated separately in the two groups.We screened 1558 consecutive ischemic stroke patients, including 154 patients with small vessel disease (lacunar infarction, 81 patients; giant lacunar infarction, 73 patients). Age (odds ratio (OR), 0.899; 95% confidence interval (CI), 0.824-0.981, p = 0.016), higher cardio-ankle vascular index (OR, 6.011; 95%CI, 2.319-15.581, p 0.001), higher uric acid (OR, 2.584; 95%CI, 1.091-6.121, p = 0.031), and lower/normal low-density lipoprotein (LDL)-cholesterol (OR, 0.718; 95%CI, 0.557-0.926, p = 0.011) were independently associated with infarct expansion in lacunar infarction patients. Concerning giant lacunar infarction, higher LDL-cholesterol (OR 1.509, 95%CI 1.083-2.103; p = 0.015) and lower/normal body mass index (OR 0.725, 95%CI 0.567-0.926; p = 0.010) were factors independently associated with infarct expansion.Risk factors for infarct expansion differed between lacunar and giant lacunar infarction. The underlying pathophysiological mechanisms for infarct expansion in these two groups should be recognized individually.

A 75-year-old man was admitted to our hospital because of repeated transient visual obscurations of greying vision. The transient visual obscurations were caused by rotating his neck or the Valsalva manoeuver, and they recovered in about 30 seconds. A few weeks later, pulsatile tinnitus of the right ear and a dull headache developed. Both ocular fundi showed papilledema, and there was significant intracranial hypertension on cerebrospinal fluid examination. He was diagnosed as having right sigmoid sinus thrombosis and a dural arteriovenous fistula with a rapid arteriovenous shunt from the right ascending pharyngeal artery and the right occipital artery to the right transverse sinus. Anticoagulant therapy was started, and coil embolization was performed. The transient visual obscurations, headache, and tinnitus improved dramatically after the procedure. We hypothesized that the transient visual obscurations were triggered by rotating the neck or performing the Valsalva manoeuver as they both increase the pressure of cerebrospinal fluid, inducing transient optic nerve ischemia and visual obscurations under mild intracranial hypertension. Transient visual obscurations are an important initial symptom of intracranial hypertension.

Background and purpose Differential diagnosis of sporadic inclusion body myositis (s-IBM) and polymyositis (PM)/dermatomyositis (DM) is difficult and can affect proper disease management. Detection of heterogeneous muscular involvement in s-IBM by muscle sonography could be a unique diagnostic feature. Methods Sonography of the lower leg and forearm was performed in patients with s-IBM, PM/DM and control subjects (n = 11 each). Echo intensities (EIs) of the adjacent muscles [medial head of the gastrocnemius versus soleus and the flexor digitorum profundus (FDP) versus flexor carpi ulnaris (FCU)] were scored by three blinded raters. The mean EIs of these muscles were compared using computer-assisted histogram analysis. Results Both evaluation methods showed high echoic signals in the gastrocnemius of patients with s-IBM. EIs were significantly different between the gastrocnemius and soleus in patients with s-IBM, but not in those with DM/PM and the controls. In the forearm, although the EI of the FDP was higher in the s-IBM group than in the other groups, the EI differences between the FDP and FCU did not differ significantly between disease groups. The difference in area under the curves to differentiate between s-IBM and DM/PM was greatest between the gastrocnemius−soleus EIs (0.843; P = 0.006). Conclusions High echoic signals in the medial gastrocnemius compared with those of the soleus are suggestive of s-IBM over PM/DM.

Background: Although subcortical infarction patients sometimes show larger infarction size than the definition of small vessel occlusion (SVO), there are no specific predictors of larger size. The aim of this study was to identify the factors, including magnetic resonance imaging (MRI) and ultrasonographic parameters, to predict larger subcortical infarction. Methods: Consecutive patients with acute supratentorial subcortical infarction were studied. Patients were classified into 2 groups (L: larger group, ≥15 mm and ≥3 slices; S: smaller group, SVO based on the TOAST classification). Clinical information, MRI findings including the presence of microbleeds, and ultrasonography findings were evaluated and compared between the 2 groups. Results: A total of 120 patients (81 male, mean 67 years old) were enrolled. The L group included 22 patients (18%), and the S group had 98 patients (82%). On neuroimaging, microbleeds were seen less frequently in the L group than in the S group (23 vs. 53%, p = 0.017), and peak systolic velocity (PSV) by transcranial color-coded sonography was faster in the L group than in the S group (121 ± 39.8 vs. 83.4 ± 25.4 cm/s, p = 0.002). On multivariate logistic regression analysis, no evidence of microbleeds (OR 4.4, 95% CI 1.41–13.68, p = 0.011) and PSV over 92 cm/s (OR 3.1, 95% CI 1.007–9.719, p = 0.049) were found to be independently associated with larger size. Conclusion: Microbleeds is related to smaller size and middle cerebral artery PSV > 92 cm/s indicate larger size in supratentorial subcortical infarcts.

Objectives The management of atrial fibrillation and deep venous thrombosis has evolved with the development of direct oral anticoagulants (DOAC), and oral anticoagulant (OAC) might influence the development or clinical course in both ischemic and hemorrhagic stroke. However, detailed data on the differences between the effects of the prior prescription of warfarin and DOAC on the clinical characteristics, neuroradiologic findings, and outcome of stroke are limited. Design The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke (ischemic stroke, transient ischemic attack, and intracerebral hemorrhage) patients receiving OAC in Japan. This study is designed to collect data on clinical background characteristics, drug adherence, drug dosage, neurological severity at admission and discharge, infarct or hematoma size, acute therapy including recanalization therapy or reverse drug therapy, and timing of OAC re-initiation. Patient enrollment started in April 2016 and the target patient number is 1000 patients. Conclusions The PASTA prospective registry should identify the status of stroke patients taking OAC in the current clinical practice in Japan.

Thrombotic microangiopathies (TMAs) are systemic microvascular occlusive disorders. The present report describes a patient with relapsing-remitting multiple sclerosis who had been treated with interferon (IFN)-β1b therapy for eight years and developed TMA. The patient presented with headache, thrombocytopenia, renal dysfunction, severe hypertension, posterior reversible encephalopathy syndrome, and gastrointestinal involvement. After discontinuation of the medication and initiation of antihypertensive treatment, the patient rapidly improved. This is the first report of TMA with gastrointestinal involvement (intestinal TMA) induced by IFN-β. The new onset of hypertension or headache requires careful attention in cases of long-term administration of IFN-β1b.

Purpose We developed a novel probe (pastable soft ultrasound probe; PSUP) attached to the neck for right-to-left shunt (RLS) detection. The purpose of this study was to evaluate the diagnostic ability of the PSUP for RLS detection by comparison with transesophageal echocardiography (TEE). Methods The subjects were patients with ischemic strokes and transient ischemic attacks who underwent TEE. Based on TEE, patients with patent foramen ovale (PFO) were divided into two groups by the number of microbubbles (MBs): small PFO (1–29 MBs) and large PFO (≥30 MBs). Then, PSUP examination of one common carotid artery (CCA) was started using a procedure similar to TEE. RLS was diagnosed by PSUP when one or more microembolic signals were found in the CCA. The detection rate by size of PFO was compared between TEE and PSUP, and the diagnostic accuracy of PSUP was calculated. Results From May 2014 to July 2016, 84 patients (63 males, median age 63 years) were included; 41 (49%) were diagnosed with PFO by TEE, while PSUP detected PFO in 31 (37%). Using TEE findings as the reference, PSUP for PFO showed sensitivity of 68%, specificity of 93%, and accuracy of 81%. On TEE, 22 patients had large PFOs, and 19 patients had small PFOs. The PSUP could identify large PFOs in grade I and II of International Consensus Criteria more accurately than small ones (58 and 86% vs. 29 and 14%, P = 0.003). Conclusions The PSUP has considerable accuracy for diagnosing large PFOs. PSUP should play an important role in detecting large PFOs.

Carotid stump syndrome is a cause of recurrent embolic stroke following occlusion of the ipsilateral internal carotid artery. The present report describes a case of recurrent cerebral embolism ipsilateral to a chronically occluded left common carotid artery (CCA), i.e., "CCA stump syndrome." Doppler color flow imaging showed anterograde flow in the left internal and external carotid arteries, which were supplied by collateral flow from the superior thyroid artery inflowing just proximal to the left carotid bifurcation. According to carotid duplex ultrasonography (CDU), a low-echoic mobile thrombus was noted at the distal stump of the occluded CCA, which presumably caused distal embolism. The low-echoic mobile thrombus dramatically changed to a homogenously high-echoic thrombus, and there was no recurrence of stroke after antiplatelet and anticoagulant therapy. This is the first report to demonstrate a CDU-verified temporal change in the thrombus at the stump in CCA stump syndrome. CDU is a noninvasive and useful technique to characterize hemodynamics, thrombus morphology, and the response to therapy.

Background/Aims: The factors related to cerebrovascular complications in cerebral venous sinus thrombosis (CVST) are controversial. We focused on venous stasis and investigated its relationship with cerebrovascular complications in CVST. Methods: CVST patients between June 2013 and October 2016 were enrolled. Relationships between cerebrovascular complications, defined as cerebral venous infarction, intracerebral hemorrhage, or subarachnoid hemorrhage, and cerebrum venous stasis and other clinical information were retrospectively analyzed. Venous stasis was evaluated by the prominence of the veins on susceptibility-weighted imaging (SWI). The cerebrum was divided into 10 regions according to the venous drainage territories, and venous stasis was quantified by adding one point for venous prominence on SWI for each region (CVST SWI score). Results: All 5 cases in the noncomplicated group had a CVST SWI score of 0. The 3 patients with CVST SWI scores higher than 0 had cerebrovascular complications. The CVST SWI scores were higher in the complicated group than in the noncomplicated group (3.0 vs. 0, p = 0.010). Seizures were seen in all patients with complications and in none of the patients without complications (3 vs. 0, p = 0.018). Conclusion: Venous stasis evaluated by SWI can help predict cerebrovascular complications in CVST. A seizure is an important initial symptom that suggests cerebrovascular complications in CVST.

Background and purpose The present study aimed to determine the frequency and time of recurrent cerebral infarct (RCI) in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF), and to clarify associated factors. Methods We retrospectively assessed and compared the clinical features of 79 consecutive patients (male, n = 56; median age, 75 y; median baseline NIHSS, 4) who were hospitalized due to AIS accompanied by AF, and who did or did not develop RCI between January 2012 and March 2015. Results Direct oral anticoagulants were administered to 59% of the patients after a median of two days from the onset of the index stroke. Stroke recurred in 10 (13%) of the 79 patients about 5 days after admission. The proportion of men was lower (30% vs. 77%, P = 0.005) and the patients were older (82 vs. 75 y, P = 0.049) in the group with RCI. Chronic kidney disease was significantly more prevalent in the group with RCI (50% vs. 16%, P = 0.025) and independently associated with RCI (OR, 6.59; 95%CI, 1.19–36.63; P = 0.031). Conclusions We found that RCI frequently develops about 5 days after admission in patients with AIS and AF and that chronic kidney disease is independently associated with RCI.

We report a patient with cerebral air embolism in whom we could perform serial brain magnetic resonance images (MRIs). A 78-year-old man was admitted to our hospital because of recurrent empyema after surgery for esophageal cancer. He suddenly demonstrated left hemiparesis in the middle of pleural lavage. After about 30 minutes from onset, the computed tomography (CT) revealed multiple air-isodense spots in the right hemisphere of the brain. After about 2 hours from onset, many hypointense spots in the right hemisphere were revealed on T2*-weighted image (T2*WI). These findings suggested cerebral air embolism. He didn't receive hyperbaric oxygen therapy because he had status epilepticus. The hypointense spots on the T2*WI became smaller and spread after 7 hours from onset and almost disappeared after 53 days. It is important to recognize that cerebral arterial air embolism is similar to multiple microbleeds and cerebral arteriovenous fistula in hypointense spots on the T2*WI.

The relationships between diffusion lesions and risk scores for patients with a Transient ischemic attack (TIA) and the optimal timing for diffusion lesion screening have not been characterized. The purpose of our study was to evaluate the appearance of diffusion-weighted imaging (DWI) lesions during follow-up examinations of patients with TIA or minor stroke without initial DWI lesions.We identified 31 patients who did not show diffusion lesions in initial DWI. A second magnetic resonance imaging (MRI) examination was performed 24 h after the initial MRI, and the patients were divided into two groups based on the results. Demographic and clinical data, including initial National Institutes of Health Stroke Scale scores, ABCD and ABCD(2) scores, and other MRI findings were evaluated. The data were analyzed using Spearman's rank tests and unpaired t tests.Ten patients (32.3 %) showed diffusion lesions on the second DWI examination. Both risk scores were higher in these patients compared with patients with negative results on follow-up DWI (P0.05, unpaired t test) and correlated with the length of the TIA (R s = 0.017, P0.05; R s = 0.003, P0.01; Spearman's rank test).Our results suggest that TIA patients with high-risk scores might be underestimated if the first MRI was performed within 24 h of symptom onset.

It is unknown whether contrast transcranial color-coded sonography of vertebral artery monitoring via the foramen magnum window (cTCCS-VA) is useful to detect right-to-left shunt (RLS). We investigated whether cTCCS-VA can be proposed as an alternative to middle cerebral artery monitoring via the temporal bone window (cTCCS-MCA) for RLS detection, as compared with contrast transesophageal echocardiography (cTEE).We evaluated 112 patients with ischemic stroke or transient ischemic attack. We compared the sufficiency of both acoustic windows in each age tertile. Then, we analyzed the accuracy of cTCCS in diagnosing an RLS for a patent foramen ovale (PFO) detected by cTEE.In the higher-age tertile, the foramen magnum window was significantly more sufficient than the temporal bone window (100% vs. 71%, p0.001). In 94 patients having both windows, diagnosis of an RLS using cTCCS-MCA revealed a specificity of 42%, and a sensitivity of 84%. Diagnosis of an RLS using cTCCS-VA revealed a specificity of 40%, and a sensitivity of 91%. Analysis of the subgroup with large PFOs revealed a specificity of 71% using both cTCCS-MCA and cTCCS-VA.cTCCS-VA should play an important role in detecting an RLS, especially in elderly stroke patients having large PFOs.

Clinical-diffusion mismatch (CDM) between stroke severity and volume of diffusion-weighted imaging (DWI) lesions seems to predict penumbra. The Alberta Stroke Program Early CT Score on DWI (DWI ASPECTS) is a simple score for identifying ischaemic lesions. The authors examined whether CDM using DWI ASPECTS can predict neurological improvement in patients with acute stroke treated with intravenous tissue plasminogen activator (t-PA).The authors enrolled consecutive patients with anterior circulation stroke treated with intravenous t-PA. The authors calculated a cut-off value for CDM using DWI ASPECTS. After excluding a group of patients with mild symptoms (National Institutes of Health Stroke Scale (NIHSS) score8), the authors divided the patients into two groups by presence or not of CDM (a positive group (P-CDM) and a negative group (N-CDM)). The authors then compared clinical characteristics including NIHSS score and modified Rankin Scale at 90 days after intravenous t-PA.Seventy-one patients (male 41, mean age 74 years) were enrolled. DWI ASPECTS was linearly related to DWI lesion volume. The authors defined CDM as NIHSS scoresor =8 and DWI ASPECTSor =7. The P-CDM group had 35 patients (61%) and the N-CDM group 22 patients (39%). NIHSS scores on admission were 15 (median) in P-CDM and 20 in N-CDM (p=0.004). NIHSS scores after intravenous t-PA improved in P-CDM but were unchanged in N-CDM (7 vs 20 at 7 days, p=0.033 on ANOVA). A favourable outcome at 90 days, defined as modified Rankin scale 0-3, was found in 46% of P-CDM patients and 14% of N-CDM patients (p=0.020).CDM determined using DWI ASPECTS may be associated with neurological improvement in patients treated with intravenous t-PA.

Symptomatic intracranial hemorrhages are typically clinically catastrophic and occur more frequently with tissue plasminogen activator (t-PA) therapy compared to without t-PA therapy. However, it has been unclear whether asymptomatic intracranial hemorrhage has clinical implications.Consecutive anterior-circulation ischemic stroke patients treated with t-PA within 3 h of stroke onset were studied prospectively. Patients with symptomatic hemorrhages were excluded from the study. To identify the presence of early recanalization and intracranial hemorrhage, as well as to measure infarction volume, MRI examinations, including diffusion-weighted imaging, T2(), FLAIR, and MRA, were performed before and 1 h, 24 h, and 5-7 days after t-PA thrombolysis. At the same time, serial NIHSS scores were obtained. The independent predictors of dramatic recovery were determined using multivariate logistic regression analysis.51 patients were enrolled in the present study. 22 patients (H group) had an asymptomatic hemorrhage. The NIHSS score of the Non-H group decreased, but that of the H group did not (11.5+/-6.5 vs. 17.1+/-6.5 at baseline, and 4.5+/-6.8 vs. 14.3+/-7.6 at 7 days; P=0.0073 for ANOVA). Asymptomatic hemorrhage was more frequently seen in non-dramatic improvement group than in dramatic improvement group (65.5% vs. 13.6%, P=0.0002). On multivariate logistic regression analysis using the variables that had a P0.1 on univariate analysis (AF, baseline NIHSS score, glucose, the presence of asymptomatic hemorrhage, ICA occlusion, early recanalization 1 h after t-PA infusion, and infarction volume 7 days after t-PA therapy), early recanalization (OR: 11.33; 95%CI: 1.064-120.704; P=0.044) and infarction volume100 cm(3) (OR: 13.56; 95%CI: 1.020-180.125; P=0.048) were independent factors for dramatic improvement, while asymptomatic hemorrhage (OR: 0.03; 95%CI: 0.002-0.537; P=0.016) was an independent negative factor.Asymptomatic hemorrhage was an independent negative factor for dramatic improvement. Asymptomatic hemorrhage after t-PA thrombolysis may be associated with neurological recovery.

Background and purpose Intravenous administration of tissue plasminogen activator (t-PA) can improve clinical outcomes in patients with acute ischemic stroke. The most important complication of t-PA therapy is intracerebral hemorrhage (ICH). The aim of this study was to use serial MRI studies to identify independent predictors of symptomatic and asymptomatic ICH after t-PA therapy. Methods Consecutive anterior-circulation ischemic stroke patients treated with t-PA within 3 h of stroke onset were studied prospectively. To identify the presence of recanalization in the occluded arteries and the presence of ICH, MRI, including diffusion weighted imaging (DWI), T2*, and magnetic resonance angiography (MRA), was performed before and 1 h, 24 h, and 5–7 days after t-PA thrombolysis. The independent predictors of ICH were determined using multivariate logistic regression analysis. Results 41 patients (21 males, 20 females; mean age, 73.2 ± 10.7 years) were enrolled, and 19 ICHs (1 symptomatic, 18 asymptomatic) were observed on T2*. The initial MRA demonstrated occluded brain arteries in 31 patients (75.6%), of which follow-up MRA at 1 h, 24 h, and 5–7 days after t-PA therapy revealed recanalization in 48.4%, 80.0%, and 90.0% of patients, respectively. The frequency of recanalization within 1 h after t-PA therapy did not differ between ICH and No-ICH groups, but the ICH group had more frequent recanalization between 1 h and 24 h after t-PA than the No-ICH group (50.0% vs. 4.5%, P = 0.001). The ICH group had arterial fibrillation (AF) more frequently than the No-ICH group (78.9% vs. 27.3%, P = 0.001). Compared to the No-ICH group, the NIHSS score was higher (16.4 ± 5.7 vs. 11.5 ± 6.5, P = 0.011) and the ASPECTS–DWI value (a normal DWI has an ASPECTS–DWI value of 11 points) was lower (7.3 ± 2.4 vs. 8.9 ± 1.9, P = 0.019) in the ICH group. Multivariate logistic regression analysis demonstrated that the presence of recanalization between 1 and 24 h after the end of t-PA infusion (OR: 20.2; CI: 1.0–340.9; P = 0.037) was the only independent predictor of ICH. Conclusion Recanalization of occluded arteries between 1 and 24 h but not within 1 h after t-PA infusion should be independently associated with symptomatic and asymptomatic ICH after t-PA therapy.

Background and purpose The mechanism of neurological deterioration in small vessel disease is unclear. We examined the relationship between neurological deterioration and change of infarct volume in acute small vessel disease. Methods We studied consecutive patients with acute supratentorial small vessel disease. Patients were classified into two groups (D: group with deterioration, N: group with no deterioration). We performed serial MRI studies, measured infarct volumes using NIH Image, and calculated the changes in infarct volume (Δ volume) between initial and follow-up diffusion-weighted imaging (DWI). Results Seventy-two patients (44 males, 68±11 years of age) were enrolled. Fifteen patients exhibited neurological deterioration (group D) and 57 patients did not (group N). Initial infarct volume was 0.66 cm 3 in group D and 0.45 cm 3 in group N ( p =0.025). Infarct volumes on follow-up DWI were 1.41 cm 3 and 0.72 cm 3 , respectively ( p =0.001). The Δ volume in group D was larger than that in group N (0.76 cm 3 vs 0.27 cm 3 , p =0.001). In order to differentiate D from N group, sensitivity specificity analysis yielded a cut-off value of Δ volume of 0.5 cm 3 for differentiation of the two groups, which exhibited a sensitivity of 80% and specificity of 84%. Multivariate logistic regression analysis demonstrated that increase in infarct volume of over 0.5 cm 3 (odds ratio; 18.0, 95% CI; 1.4 to 270, p =0.027) was independently associated with neurological deterioration in patients with acute small vessel disease. Conclusions Enlargement of infarct volume may contribute to neurological deterioration in acute small vessel disease.

Muscle ultrasound is a useful tool of the neuromuscular disease. On muscle ultrasound, we can detect the affected muscle as increase of muscle echo intensity because of the fibrosis and fatty infiltration. Muscle atrophy and thickened muscle fascia are also visualized with muscle ultrasound. Another advantage of muscle ultrasound compared to other imaging technique is to visualize muscle movement, such as fasciculation. In this paper we review the findings of muscle ultrasound in normal muscle and affected muscle and discuss the possibilities and limitations of muscle ultrasound.

Ischemic vessel signs (IVS) can be detected on 3-tesla T2(*)-weighted magnetic resonance images as a vessel enlargement at the territory of acute ischemia caused by major vessel occlusion or stenosis. Here, we studied changes in IVS before and after recanalization by the administration of intravenous recombinant tissue plasminogen activator (IV rtPA), carotid artery stenting or percutaneous transluminal angioplasty in patients with major vessel occlusion or stenosis. We performed magnetic resonance imaging for all patients treated by IV rtPA at the time of admission, shortly after and 24-72 hours after treatment with IV rtPA. We reviewed the IVS to assess its natural course of IVS by assessing patients who did not recanalize. IVS tended to disappear after recanalization. Conversely, in patients without recanalization, IVS did not disappear shortly after IV rtPA; rather, it disappeared 24-72 hours after IV rtPA, especially in the presence of complete infarction. Recanalization by IV rtPA or endovascular treatment contributed to improved clinical deficits or the prevention from further progression. IVS can be a parameter of misery perfusion and an important factor to detect the patients who have an indication of treatment for recanalization.

Objective Progressive atrophy and loss of motor axons is a hallmark of amyotrophic lateral sclerosis (ALS). Limited sonographic data are available on potential detection of atrophy of peripheral nerves and nerve roots in ALS. Methods Patients with either definite or probable ALS and control subjects underwent sonographic evaluation of the cervical roots (C5, C6, and C7) and peripheral nerves (median and ulnar nerves) on the right. These diameters and cross-sectional areas (C6, median, and ulnar nerves) were compared. Results The diameters and cross-sectional areas were consistently smaller in ALS than in controls. No correlation was present between the sonographic parameters and the disease severity, disease duration, age, or gender. The overall sensitivity and specificity tended to be greater in the cervical nerve roots than in the peripheral nerves. Conclusions This study shows atrophy of cervical nerve roots and peripheral nerves in ALS detected by sonography. Cervical nerve roots might be more appropriate to detect motor axon loss than peripheral nerves. Significance Sonographic evaluation of nerve roots and peripheral nerves may be a useful disease marker in ALS to confirm the diagnosis and to potentially monitor the disease progression.

Background and Purpose— The brush sign (BS) is the enlargement of medullary veins on 3-T T2*-weighted MRI seen in patients with ischemic stroke because of major cerebral artery occlusion. However, the clinical relevance of BS in patients with acute stroke remains unclear. We assessed the correlation between detecting BS with the development of hemorrhagic transformation after intravenous thrombolysis. Methods— We enrolled consecutive patients with M1 or M2 occlusion treated with intravenous tissue plasminogen activator. We classified the patients into 2 groups: the group positive for BS (P-BS) and the group negative for BS (N-BS). We investigated the differences in MRI findings and the clinical outcome between the 2 groups. Results— The subjects consisted of 36 patients (19 men; mean age, 74.7 years). Twenty-one patients (58%) had M1 occlusion, and 15 (42%) had M2 occlusion. Twenty-five patients (69%) were classified into the P-BS group and 11 (31%) into the N-BS group. Recanalization was observed in 15 (60%) and 10 (90%) patients in the P-BS and N-BS groups, respectively ( P =0.116). Hemorrhagic transformation on MRI was observed more frequently in the P-BS group than in the N-BS group (64% versus 18%; P =0.027). A good outcome (mRS, 0–1) at discharge was found in 24% of patients in the P-BS group and in 45% of patients in the N-BS group ( P =0.152). A multivariate logistic regression analysis revealed that the presence of BS (odds ratio, 9.08; 95% confidence interval, 1.4–59.8; P =0.022) was independently associated with hemorrhagic transformation. Conclusions— BS may predict the development of hemorrhagic transformation in patients with acute stroke treated with intravenous tissue plasminogen activator.

Anandamide loses its cannabimimetic activities upon hydrolysis to arachidonic acid and ethanolamine. So far the anandamide hydrolyzing activity widely distributed in mammalian organs has been attributed exclusively to an enzyme referred to as anandamide amidohydrolase with an optimum pH around 9. We found another enzyme hydrolyzing anandamide in a human megakaryoblastic cell line (CMK). The enzyme present in the 12 000 ×g pellet of the cell homogenate was solubilized by freeze-thaw. The solubilized enzyme showed an optimal pH around 5, and was almost inactive at alkaline pH. The enzyme activity was increased by the addition of dithiothreitol. In contrast, anandamide amidohydrolase of RBL-1 cells was mostly insoluble even after freeze-thaw, showed an optimal pH at 9, and was not affected by dithiothreitol. Furthermore, the enzyme of CMK cells was much less sensitive to phenylmethylsulfonyl fluoride and methyl arachidonoyl fluorophosphonate potently inhibiting anandamide amidohydrolase, and effectively hydrolyzed palmitoylethanolamide, which was a poor substrate for anandamide amidohydrolase. Thus, the enzyme of CMK cells is distinguishable from anandamide amidohydrolase.

BACKGROUND We investigated how many contrast-transcranial Doppler (c-TCD) examinations should be performed on different days in patients with acute stroke. METHODS Consecutive acute stroke patients within 24 hours of onset were enrolled. Presence of RLS was examined using c-TCD examinations on days 1, 7, and 14. Each c-TCD examination used one test without Valsalva maneuver (VM) and three tests with VM. Patients were diagnosed with RLS when TCD detected ≥1 microembolic signal on ≥1 c-TCD examination on any of the days 1, 7, or 14. RESULTS One hundred seventy patients (105 men [62%]; median age, 74 [IQR, 66–81] years) were enrolled. RLS was diagnosed in 45 patients (26%). RLS was identified on day 1 in 30 patients (18%), on day 7 in 28 patients (16%), and on day 14 in 23 patients (14%; P= .143). Detection rate of RLS by combining day 1 and 7 examinations was significantly higher than that of day 1 alone (25% vs 18%, P < .001). However, the rate did not increase when results of day 14 were added (25% vs 26%, P= .250). CONCLUSIONS c-TCD examinations should be performed on at least two different days to assess the prevalence of RLS.

Detection rate of right-to-left shunt (RLS) may be lower in stroke patients with atrial fibrillation (AF) than in those without AF. This may be due to the mechanism of embolic stroke in AF patients that involves cardiac embolus rather than paradoxical embolism due to RLS. Patients with AF frequently have subclinical heart failure, resulting in elevated left atrial (LA) pressure, which may prevent opening of a patent foramen ovale (PFO). We aimed to investigate whether the detection rate of RLS in stroke patients with AF was affected by elevated LA pressure.We enrolled consecutive acute stroke patients with AF and, as controls, consecutive acute stroke patients without AF. RLS was diagnosed using contrast transcranial Doppler. To assess LA pressure, the ratio of early mitral inflow velocity to diastolic mitral annular velocity (E/E') was measured using transthoracic echocardiography.We enrolled 171 patients with AF (AF group, age, 78 years [IQR, 70-83]) and 171 patients without AF (control group, age, 73 years [IQR, 64-81]). RLS was observed less frequently in AF patients than in the control group (9% vs. 18%, p=0.024). E/E' ratio was higher in AF patients (13.1 [9.4-17.4] vs. 10.9 [8.2-13.7], p0.001). Among controls, E/E' ratio did not differ between patients with and without RLS (11.8 [8.5-12.9] vs. 10.8 [8.0-13.9], p=0.884). Conversely, in AF patients, E/E' ratio was lower in patients with RLS than in those without RLS (9.0 [8.3-12.6] vs. 13.6 [10.2-18.1], p=0.008). Multivariate regression analysis demonstrated that E/E' ratio of11.0 was an independently associated with RLS (OR 4.61, 95%CI 1.21-17.62, p=0.025).RLS was detected less frequently in AF patients than in controls. Elevated LA pressure was associated with the absence of RLS in AF stroke patients and may prevent opening of a PFO.

Background and Purpose We investigated whether the plasma brain natriuretic peptide (BNP) level on admission can serve as a biological marker of in-hospital death in patients with acute ischemic stroke. Methods We prospectively enrolled 335 consecutive patients (125 females; mean age, 72.3 years) with acute ischemic stroke within 24 hours of onset and measured plasma BNP on admission. Patients were divided into two groups: the deceased group, who died during hospitalization; and the survival group. The factors associated with in-hospital death were investigated by multivariate logistic regression analysis. Results Death was observed in 20 (6.0%) patients. Frequencies of atrial fibrillation, cardioembolism, the use of diuretics before ischemic stroke, the use of digitalis before ischemic stroke, National Institutes of Health Stroke Scale (NIHSS) score on admission, glucose level, and D-dimer were significantly higher in the deceased group than in the survival group. On the other hand, albumin was significantly lower in the deceased group than in the survival group. The mean ± SD of the plasma BNP level of the deceased group was significantly higher than that of the survival group (731.5±1,070.9 vs. 213.1±384.5 pg/mL, p=0.001). The optimal cut-off level, sensitivity, and specificity of BNP levels to distinguish the deceased group from the survival group were 240 pg/mL, 75.0% and 73.0%, respectively. Multivariate logistic regression analysis demonstrated that a NIHSS score of >13 (odds ratio [OR], 4.87; 95% confidence interval, 1.54 to 15.44, p=0.007) and plasma BNP level of >240 pg/mL (OR, 4.67; 95% confidence interval, 1.28 to 17.09, p=0.020) were independent factors associated with in-hospital death. Conclusion The plasma BNP level on admission can predict in-hospital death in patients with acute ischemic stroke.

Aortic complicated lesions (ACLs) should be associated with cerebral infarction. Our aim was to develop a simple clinical scale (ACL scale) to predict the presence of ACL. Consecutive stroke patients undergoing transesophageal echocardiogram (TEE) examination were prospectively enrolled. We defined ACL as the presence of >4 mm wall thickness, ulceration or mobile plaque in aortic arch. We also examined carotid intima-media thickness (IMT), ankle-brachial index (ABI) and brachial-ankle pulse-wave velocity (baPWV). We compared the clinical characteristics of patients with ACL (ACL group) and without ACL (non-ACL group), and devised a new ACL scale to predict the presence of ACL. In all, 165 patients (male 108, age 66.9 years) were enrolled and of these, 38% had ACL. The patients of the ACL group were older than those of the non-ACL group (73.0+/-10.2 vs. 63.1+/-13.6 years, P=0.001). Peripheral artery disease (PAD) was more frequent in the ACL group (18 vs. 4%, P=0.004). IMT was thicker in ACL group than in the non-ACL group (1.29+/-0.74 vs. 1.11+/-0.79 mm, P=0.002), and baPWV was higher in the ACL group (2164.2+/-643.2 vs. 1833.7+/-492.9 cm s(-1), P=0.001). We used three variables for determining the ACL scale score; (1) age >70, (2) presence of PAD and (3) smoking. The frequencies of ACL associated with ACL scale scores were as follows: 6% of patients with ACL scale score 0, 40% with score 1, 58% with score 2 and 100% with score 3. The ACL scale can predict the presence of aortic complicated lesions.

We report a case of a 49-year-old woman with headache who was diagnosed with cerebral venous thrombosis (CVT) of the superior sagittal and right transverse sinuses. Serial gradient recalled-echo T2*-weighted imaging (T2*WI) studies demonstrated dynamic changes of thrombosed segments. T2*WI is useful not only as a diagnostic tool for CVT, but also in evaluating changes to thrombus.

BACKGROUND AND PURPOSE The aim of this study was to investigate whether physiological factors, including body mass index (BMI), are associated with detection of right-to-left shunt (RLS) by contrast transcranial Doppler ultrasonography (c-TCD). METHODS After prospective c-TCD for stroke patients, we compared clinical backgrounds between patients with positive and negative results for RLS. After counting microembolic signals (MES), RLS were functionally graded as follows (grade 0 = 0 MES, grade I = 1-10 MES, grade II = 11-30 MES, grade III = 31-100 MES if countable, grade IV = over 100 MES or uncountable like a shower. RESULTS Subjects comprised 584 patients (203 men, 381 women) with a mean age of 67.9 ± 11.1 years. RLS was detected in 134 of 584 patients (23%). In univariate analysis, mean BMI was 22.1 in patients with RLS and 23.3 in those without RLS (P= .004). Mean BMI in concordance with RLS grade gradually decreased (grade 0; 22.7, grade I; 20.8, grade II; 20.1, grade III; 19.6, P= .001). After performing the Valsalva maneuver, mean BMI in concordance with RLS grade linearly increased (grade I; 20.6, grade II; 23.2, grade III; 24.8, grade IV; 25.8, P < .001). CONCLUSION Although smaller body size may be associated with detection of RLS, a patient with significant RLS (grade III or IV) had larger body.

Congestive heart failure is a risk factor for ischemic stroke. Brain natriuretic peptide (BNP) is used as a biological marker of heart failure. We hypothesized that heart failure was associated with the onset of ischemic stroke patients with atrial fibrillation (AF).Between June 2006 and December 2007, we prospectively enrolled consecutive acute ischemic stroke patients with AF within 24 h of onset. Plasma BNP was measured twice, on admission and on days 28 or at discharge. As a control, we measured plasma BNP of chronic phase of stroke outpatients with AF. We investigated whether plasma BNP was elevated in the acute phase of stroke.One hundred and nine patients (58 females; mean age, 76.3 years) were enrolled in the present study. Mean+/-SD of NIHSS score on admission and mRS score at discharge were 12.6+/-8.3 and 3.7+/-1.8, respectively. The interval from stroke onset to plasma BNP measurement on admission was 6.8+/-6.3 h. Moreover, follow up BNP was measured at mean of 26+/-9 days after stroke onset. The plasma BNP level in the acute phase of stroke was significantly higher than that of the subacute phase of stroke (median (interquartile range, IQR) 299.0 (176.8-469.5) vs. 149.5 (68.1-347.0) pg/ml, p0.001). There was no significant difference in plasma BNP level between the subacute phase of stroke and control group (median (IQR) 149.5 (68.1-347.0) vs. 165.0 (64.6-224.0) pg/ml, p=0.543).Plasma BNP was elevated in the acute phase of stroke. Heart failure may be associated with the onset of ischemic stroke patients with AF.

A community-based study was conducted to estimate the prevalence of atrial fibrillation (AF) in Japanese adults agedor=40 years in Kurashiki-city and to examine associated risk factors.Adult residents (or=40-year-old) were examined in the Kurashiki-city Annual Medical Survey (KAMS) provided by the Kurashiki-city Public Health Center from May to December 2006. KAMS consisted of medical interviews, physical examination, blood testing and electrocardiography to assess the presence of AF. All participants were divided into AF and non-AF groups, their clinical characteristics compared, and the risk factors associated with AF investigated. Of 246,246 adult residents, 41,436 (age: 72.1+/-11.3 years; 13,963 men) underwent the KAMS. Estimated overall prevalence of AF was 1.6%. Multivariate analysis demonstrated that AF was independently associated with cardiac disease (odds ratio (OR), 9.00; 95% confidence interval (CI), 7.65-10.6; p0.001), chronic kidney disease (OR, 1.76; 95%CI, 1.49-2.07; p0.001), male sex (OR, 1.59; 95%CI, 1.34-1.85; p0.001), and diabetes mellitus (OR, 1.46; 95%CI, 1.20-1.78; p0.001). Hypercholesterolemia was highly associated with the absence of AF (OR, 0.54; 95%CI, 0.45-0.64, p0.001).Prevalence of AF in Japan is approximately 1.6%, lower than that in Western populations. Male sex, and cardiac and chronic kidney diseases are associated with the presence of AF.

Although both atrial fibrillation (AF) and decreasing glomerular filtration rate (GFR) are strongly related to advanced age and share common associated vascular risk factors, few studies have explored the relation between AF and GFR. From residents (ageor=40 years) in Kurashiki City, a total of 41,417 subjects (median age 72 years; 13,956 men) were enrolled in the Kurashiki City Annual Medical Survey from May to December 2006. The estimated overall prevalence of AF was 1.6% (2.8% in the low-GFR tertile, 1.2% in the middle tertile, and 0.9% in the high tertile, p0.001). After all subjects were categorized into age tertiles (age thresholds 68 and 76 years), AF was identified in 0.9% in the low-GFR tertile, 0.6% in the middle tertile, and 0.5% in the high tertile in the low-age tertile (p = 0.018); 2.6% in the low-GFR tertile, 1.2% in the middle tertile, and 1.1% in the high tertile in the middle-age tertile (p0.001); and 3.9% in the low-GFR tertile, 2.4% in the middle tertile, and 1.7% in the high tertile in the high-age tertile (p0.001). The odds ratio for AF adjusted for age, gender, vascular risk factors, cardiac disease, and hemoglobin was 1.91 (95% confidence interval 1.54 to 2.38, p0.001) for the low-GFR tertile versus the high tertile and 1.12 (95% confidence interval 0.88 to 1.42, p = 0.364) for the middle-GFR tertile versus the high tertile. The prevalence of AF gradually increased with decreasing GFR. In conclusion, AF appears to be associated with decreasing GFR.

Background: Contrast transesophageal echocardiography (c-TEE) and contrast transcranial Doppler (c-TCD) are useful diagnostic tools for detecting right-to-left shunts (RLS). However, the diagnostic accuracy of c-TCD for patent foramen ovale (PFO) remains uncertain. We investigated the relationship between the size of PFO determined by c-TEE and c-TCD findings and assessed the detectable rate of RLS by c-TCD. Methods: We assessed RLS three times using simultaneous c-TCD and c-TEE in 107 patients (321 examinations). We classified all of ultrasound examinations into three groups by size according to microbubbles on c-TEE, such as no PFO (0 microbubble), small PFO (1–29 microbubbles) and large PFO (≥30 microbubbles). We also calculated the number of microembolic signals (MES) on c-TCD and evaluated the association between PFO size on c-TEE and MES count on c-TCD. Results: In the present study, c-TEE detected RLS in 105 (33%; small PFO, n = 78; large PFO, n = 27), and c-TCD detected RLS in 49 (15%) of 321 examinations. Among 78 examinations with small PFO, MES were found in only 19 (24%) on c-TCD. In contrast, of all 27 examinations with large PFO, MES were found on c-TCD. Also, c-TCD were able to detect MES in 3 of 216 examinations among the no-PFO group. When ≥2 MES on c-TCD was established as the cutoff to predict large PFO on c-TEE, the sensitivity, specificity and accuracy were 96.3, 96.8, and 96.9%, respectively. Conclusion: When two or more MES were determined by c-TCD, large PFO could be accurately diagnosed.

A 70-year-old man with right hemiparesis (NIHSS score 15) was admitted to our hospital 1 h after onset. Diffusion-weighted imaging (DWI) revealed a hyperintense lesion in the left corona radiata and magnetic resonance angiography (MRA) revealed occlusion of the left middle cerebral artery (MCA). At 2.5 h after onset, his neurological deficits dramatically improved (with NIHSS score change from 15 to 2). Immediately thereafter, follow-up MRI revealed that the hyperintense lesion on DWI had disappeared, though the left MCA occlusion remained. By the end of follow-up MRI examination, his neurological deficits had completely disappeared. We report here the patient with transient ischemic attack with a reversible ischemic lesion on DWI without early arterial recanalization.