Search

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.

The authors have requested that this preprint be removed from Research Square.

COL4A1-related disorders are characterized by a higher incidence of cerebral hemorrhage than other hereditary cerebral small vessel diseases. Accumulating data have shown broad phenotypic variations, and extracerebral hemorrhages have been linked to these disorders. Moreover, the coexistence of neural tumors has been described. Here, we report a Japanese family with a novel COL4A1 variant, including a patient with recurrent epistaxis and glioblastoma.

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.

Background and Purpose: We aimed to investigate the differences in weekly variations of stroke occurrence between hyper-acute ischemic stroke patients with and without regular employments (RE), and the impact of RE on outcome. Methods: Consecutive symptomatic ischemic stroke patients with < 4.5 h from onset to door between October 2012 and May 2018 were enrolled. All the situations of employment on admission were obtained from interviews with the participant or substitute guardians. First, we divided the patients into with and without RE to evaluate the differences in weekly variations of stroke occurrence. Second, we divided the same patients into with and without favorable outcome (mRS score of 0 to 2 at 3 months from the onset) to evaluate the impact of RE on outcome. Results: We screened 1,249 consecutive symptomatic ischemic stroke patients, including 385 patients (292 (76%) male, median age 67 years) with hyper-acute ischemic stroke. Of all, 251 patients (65%) were included in RE group. In the multivariate analysis, patients with RE were more likely to develop strokes on Monday compared to that on Sunday and public holiday (OR 2.841, 95% CI 1.145-7,049, p = 0.024, Figure A). In the multivariate analysis, the factors associated with favorable outcome were low NIHSS score on admission (OR 0.909, 95% CI 0.857-0.964, p = 0.001), not receiving endovascular therapy (OR 0.175 95% CI 0.069-0.444, p p = 0.039, Figure B). Conclusions: There were dramatic differences in weekly variations of hyper-acute ischemic stroke occurrence between patients with and without RE. Monday seems to be “a black day” for ischemic stroke patients with RE. RE had a positive impact on outcome in hyper-acute ischemic stroke.

Background and Purpose: Unilateral spatial neglect (USN) is often observed in ischemic stroke patients suffered their right parietal lobe. USN is an obstacle to undergo rehabilitation smoothly, then might influence the recovery of activities of daily living (ADL) after stroke. We aimed to clarify the association between the presence of USN after ischemic stroke and the ADL improvement. Methods: Consecutive patients with first-ever ischemic stroke and left limb paralysis who admitted to within 7 days from onset during February 2011 and March 2019 were included. Patients met the following criteria were excluded: mRS ≥3 before onset, NIHSS >15 on admission, without left limb paralysis, and missing NIHSS or functional independence measure (FIM) score on admission. Multiple regression analysis was performed to investigate the association between FIM efficiency score of acute phase and following factors: age, sex, acute reperfusion therapy (using an intravenous infusion of recombinant tissue plasminogen activator and/or endovascular therapy), FIM score on admission, and other clinical characteristics. All data were collected retrospectively using our electrical health record. Results: 721 ischemic stroke patients with left limb paralysis (320 women, median age 76) were included. Median FIM efficiency score was significantly lower in patients with USN than without USN (n=240, 481; 0.83 vs 1.63, respectively). Multiple regression analysis showed that USN, age, and acute reperfusion therapy were significant prognostic factors of FIM efficiency (coefficient and 95% confidence interval [CI]: -0.135 [-0.771 to -0.153], -0.106 [-0.022 to -0.002], and 0.224 [0.136 to 0.305], respectively). Conclusions: USN significantly influence the recovery of ADL after ischemic stroke. Clinicians should adequately evaluate USN after stroke and undergo USN-specific rehabilitation for them to optimize the effect of post-stroke rehabilitation. USN-specific rehabilitation might lead to better FIM efficiency.

Background and Purpose Early hematoma expansion (HE) is not rare in intracerebral hemorrhage (ICH) patients, but detecting those patients with high risk of HE is challenging. The aim of this retrospective study was to investigate the factors associated with HE in acute ICH patients, and to develop a simple predictive scale for HE. Methods We retrospectively reviewed consecutive patients with primary ICH, who received an initial non-contrast computed tomography (CT) scan within 24 hours from symptom onset. Patients underwent follow-up CT scans at 6 hours, 24 hours, and 7 days after admission. We compared the clinical characteristics of patients with and without HE (defined as an increase in intracerebral hemorrhage volume >33% or an absolute increase >6 mL on follow-up CT scans), and performed a logistic regression analysis to determine the predictors of HE. Results A total of 118 patients (78 men; median age 63 years; interquartile range 54–73) were included in our study. HE was observed in 30 patients (25%). HE patients showed higher rates of anticoagulant use (20% vs. 2%, respectively; P=0.003), high National Institutes of Health Stroke Scale on admission (13 vs. 7, respectively; P=0.001), and high plasma glucose (141 mg/dl vs. 113 mg/dl, respectively; P=0.001) compared with patients without HE. After multivariate logistic regression analysis, we selected three factors for defining the NAG scale (1 point as baseline National Institutes of Health Stroke Scale ≥10, 1 point as anticoagulant use, and 1 point as plasma glucose ≥133 mg/dL). The frequencies of HE associated with the NAG scale scores were as follows: score 0, 4%; score 1, 25%; score 2, 60%; score 3, 100%. Conclusion Stroke severity, hyperglycemia, and anticoagulation use were factors independently associated with HE. The NAG scale consists of readily available factors and can predict HE.

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— This study’s objective is to determine if nonstenotic carotid plaque of Methods— This was a cross-sectional observational study. We identified consecutive patients with anterior circulation embolic stroke of undetermined source (ESUS), excluding stroke in multiple vascular territories. Using ultrasonography, we measured the internal carotid plaque size and stenosis for each patient. We dichotomized the plaque size at several predefined thresholds and calculated the frequency of the plaque size and morphology above each threshold ipsilateral versus contralateral to the stroke site. Results— We included 53 patients with unilateral anterior circulation ESUS. Initially, we found that plaque with a thickness ≥1.5 mm was present ipsilateral to the stroke site in 59% of the patients, and present contralateral to the stroke site in 42% of the patients (31/53 versus 22/53 patients; P =0.049). Plaque with low echo likewise had a similar prevalence when present ipsilateral (9%) and contralateral (4%) to the stroke site (5/53 versus 2/53; P =0.25). Conclusions— Internal carotid artery plaque with a thickness ≥1.5 mm but that is nonstenotic (

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.

Background: The relationship between cerebral microbleeds (CMBs) and risk of early recurrence of ischemic stroke in patients with transient ischemic attack (TIA) or ischemic stroke is still controversial, and as is the effect for the prognosis. Our aim is to verify the relationship between CMBs and outcome in patients with TIA and minor ischemic stroke. Methods: We retrospectively reviewed consecutive patients with non-cardiogenic TIA and minor ischemic stroke (NIHSS Results: A total of 374 patients (279 men, median age 67 years old) were enrolled in our study. CMBs was observed in 152 patients (41%). Outcome was significantly poor in patients with CMBs (11% vs 3%, P=0.002). Stroke recurrence was frequently observed in patients with CMBs (13% vs 7%, P=0.041). Increased CMBs burden is lineally associated with poor outcome in comparison with absent CMBs (Figure 1). The multivariate analysis revealed that the CMBs was independently associated with poor outcome (OR, 3.86; 95%CI, 1.29-11.53; P=0.015). Conclusion: CMBs is the important factor for poor outcome in TIA and minor ischemic stroke, especially in increased CMBs burden patients.

Background and Purpose: The purpose of this study was to determine risk factors for lacunar and giant lacunar infarction and to clarify differences in pathophysiological mechanisms for these two groups. Methods: Patients were selected from a comprehensive stroke center with ≤24 h from onset to initial magnetic resonance imaging (MRI) with lacunar and giant lacunar infarction. All patients underwent second MRI during hospitalization. Infarct expansion was defined as present when the area of the diffusion-weighted imaging (DWI)-positive region on second MRI exceeded that on the initial MRI. To calculate the area of the DWI-positive region, we manually traced each region of interest and calculated the DWI-positive region area in each slice. Infarct size was calculated and compared by the positive region on DWI. Factors related to infarct expansion were evaluated separately in the two groups. Results: We screened 950 consecutive ischemic stroke patients, including 106 patients with small vessel disease (lacunar infarction, 54 patients; giant lacunar infarction, 52 patients). High cardio-ankle vascular index (odds ratio, 6.255; 95% confidence interval, 1.791-21.846; p = 0.004) was independently associated with infarct expansion in lacunar infarction patients (Figure 1A). Concerning giant lacunar infarction, high concentration of low-density lipoprotein-cholesterol (odds ratio, 1.923; 95% confidence interval, 1.158-3.194; p = 0.012) and low/normal body mass index (odds ratio, 0.714; 95% confidence interval, 0.515-0.989; p = 0.042) were factors independently associated with infarct expansion (Figure 1B). Conclusions: 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.

Background and Purpose: Nontraumatic convexal subarachnoid hemorrhage (cSAH) rarely occurs concomitant with acute ischemic stroke. The purpose of this study was to investigate the incidence, imaging findings, clinical backgrounds, and outcomes of hyperacute ischemic stroke with cSAH. Methods: Patients were selected from a comprehensive stroke center with ≤4.5 h from onset to door with symptomatic ischemic stroke between October 2012 and May 2018. All patients underwent CT and/or MRI on admission and we reviewed them to identify cSAH. Follow-up CT and/or MRI were also reviewed. cSAH caused by trauma, detected after thrombolysis or endovascular treatment, and accompanied with intracerebral hemorrhage was excluded. Retrospective review of cSAH incidence, imaging findings, clinical backgrounds, and outcomes was performed. Results: We screened 1249 consecutive symptomatic ischemic stroke patients, including 466 patients with ≤4.5 h from onset to door (342 (73%) male, median age 68 years). Of 466 hyperacute ischemic stroke patients, cSAH was observed in 5 (1.1%) patients (5 male, median age 49 years): 3 were detected on admission and the other was detected at follow-up. None had any meningeal irritation signs, and all were detected incidentally. Four patients (case 1-4) were diagnosed as arterial infarction, and 1 as venous infarction. Of the 4 arterial infarction patients, arterial stenosis or occlusion was observed ipsilaterally to the cSAH (Figure). In addition, of the 4 arterial infarction patients, hyperintense vessel signs were observed on FLAIR imaging on admission suggesting retrograde flow via collateral vessels, or slow flow (Figure). In all, cSAH disappeared gradually, and outcomes were favorable (modified Rankin Scale 0-1 at 3 months from the onset). Conclusions: cSAH was accompanied with approximately 1% of hyperacute ischemic stroke. Patients with arterial infarction and cSAH had arterial stenosis or occlusion ipsilaterally to cSAH.

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.

Background and Purpose: The availability of direct-acting oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF) and venous thromboembolism (VTE) has changed the therapeutic landscape of anticoagulation therapy, but the guideline-based recommendation of anticoagulation therapy for the acute stroke patients with VTE is unclear. Our aim of this study is to survey clinical characteristics of acute stroke patients with VTE in new treatment paradigms including DOACs. Methods: Subjects were acute stroke patients within 7 days from onset with VTE detected by enhanced CT and/or ultrasound of leg veins. VTE evaluation was performed for the patients as follows; presence of right-to-left shunts by transcranial Doppler, elevation of D-dimer, and suspected embolic stroke of undetermined source. We analyzed the following information: 1) the prevalence of VTE among acute stroke patients, 2) clinical information of VTE (i.e. subtype and symptom of VTE), 3) treatment details for stroke and VTE, 4) hemorrhagic complication after VTE treatment. Results: From October 2012 to June 2017, we registered 1077 acute stroke patients. We underwent the VTE evaluation for 226 patients (21%). Of them, 65 patients (39 female, mean age of 76 years, 6% of all patients, and 29% of patients with examination) had VTE (deep vein thrombosis (DVT); 52, pulmonary embolisms (PE); 2, DVT+PE; 11). In 65 patients with VTE, ischemic stroke was 60 cases. Antiplatelet agents were given for 35 of these 60 cases before starting therapy for VTE. Medications for VTE were as follows; 29 cases with DOACs, 14 with warfarin, 7 with warfarin following heparin, and 9 with heparin alone. Hemorrhagic complication occurred in 3 of 60 case of ischemic stroke with VTE (5%). One case had intraventricular hemorrhage after starting DOAC following 200mg aspirin, and muscle hematoma was found in the other two cases using warfarin following heparin. Conclusions: Prevalence of VTE was 6% of acute stroke patients in our preliminary survey. After medication for acute ischemic stroke with VTE, 5% of them had hemorrhagic complication. We should choose anticoagulation therapy for acute stroke patients with VTE focused on former use of antiplatelet drug and hemorrhagic complication.

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.

Introduction: While the examination for the evaluation of right-to-left shunt (RLS) using contrast transcranial Doppler (TCD) is useful, insufficient temporal bone window interrupts the adequate TCD examination for precise diagnosis of RLS. Thus, we developed a novel probe (paste-able soft ultrasound probe; PSUP) attached to the cervix for RLS diagnosis. Hypothesis: Monitoring at carotid artery using PSUP can detect greater number of contrast microembolic signals (cMES) than that of TCD. Methods: Subjects were patients with ischemic stroke or transient ischemic attack who had one and more cMES in middle cerebral artery detected by screening test of TCD on admission. PSUP was a 2.0-MHz center frequency and had an equal property with TCD transducer. The shape was thin, soft, and square modified for adequate attachment to the neck. We monitored blood flow of unilateral middle cerebral artery by TCD and ipsilateral common carotid artery by PSUP simultaneously. After injection of saline agitated with air in the right antecubital vein, we performed single test without Valsalva maneuver (VM) and triple tests with VM. And then, we compared the number of cMES between PSUP and TCD among each patient. Results: We performed 48 simultaneous PSUP and TCD examination (12 studies without VM, and 36 studies with VM) on 12 patients (11 male, median age of 49 years) without any complication. The number of cMES on PSUP was significantly larger than that of TCD in all of 48 examination (345 vs. 206, p Conclusions: In order to evaluate the RLS, PSUP examination at common carotid artery is a powerful approach in comparison with TCD. For patients without sufficient temporal bone window, PSUP should play an important role of RLS diagnosis.