Small ischemic lesions accompanying intracerebral hemorrhage: The underlying influence of old lacunes and polyunsaturated fatty acids.

BACKGROUND AND AIMS: Small ischemic lesions (SILs) accompanying intracerebral hemorrhage (ICH) might be induced by small-vessel vulnerability and hypercoagulation. Some polyunsaturated fatty acids (PUFAs) have been associated with hypercoagulation in cardiovascular diseases. Our aim here is to determine how pre-existing small-vessel disease (SVD) and PUFAs may affect SILs. METHODS AND RESULTS: We screened consecutive ICH patients (October 2012-December 2021) meeting two inclusion criteria: (1) the patients were hospitalized for acute ICH and were undergoing magnetic resonance imaging and (2) the patients' PUFA measurements were available. After excluding patients with isolated intraventricular hemorrhage, we evaluated whether three SVD markers (white matter hyperintensities, old lacunes, cerebral microbleeds) and PUFAs might be associated with the development of SILs. We selected 319 participants from 377 screened consecutive ICH patients (median age = 64, males = 207 [65 %]). Of the 319 patients, 45 patients (14 %) developed SILs. In a multivariable logistic regression analysis, the factors associated with SILs were old lacunes (OR 3.255, 95 % CI 1.101-9.622, p = 0.033) and DHA/AA ratio (OR 0.180, 95 % CI 0.046-0.704, p = 0.013). Furthermore, in our multivariable analysis using DHA/AA ratio tertiles with and without SILs, we observed a linear trend between SILs and the Higher Tertile of the DHA/AA ratio (DHA/AA ratio Mid-Tertile: OR 1.330, 95%CI 0.557-3.177, p = 0.521, and DHA/AA ratio Lower Tertile: OR 2.632, 95%CI 1.124-6.162, p = 0.026). CONCLUSION: The presence of old lacunes and lower DHA/AA ratios might be associated with SILs accompanying ICH.

Urinary Immunoglobulin G Is Associated with Deep and Infratentorial Cerebral Microbleeds in Stroke Patients.

BACKGROUND: Cerebral microbleeds (CMBs) detected on susceptibility-weighted imaging (SWI) are associated with cerebral small vessel disease. Chronic kidney disease and microalbuminuria have been associated with the presence of CMBs in stroke patients. Urinary immunoglobulin G (IgG) is measured to document glomerular injury; however, the relationship between urinary IgG and CMBs is unknown. METHODS: We retrospectively enrolled consecutive patients who had been admitted with transient ischemic attack (TIA) or ischemic stroke and identified those who had undergone SWI and a spot urine test. The location of CMBs was classified on magnetic resonance imaging as strictly lobar, deep/infratentorial (D/I), or mixed areas. We analyzed the association between urinary IgG and the presence and location of CMBs. RESULTS: We included 298 patients (86 female, median age 70 years, median eGFR 65.8 mL/min/1.73 m2). Positive urinary IgG and CMB results were found in 58 (19%) and 160 patients (54%), respectively. Urinary IgG positivity was significantly associated with CMBs compared with non-CMBs (28% vs. 9%, p < 0.001), and with D/I or mixed CMBs compared with non-D/I or mixed CMBs (34% vs. 10%, p < 0.001). Multivariate analysis revealed that urinary IgG and hypertension positivity were strongly associated with D/I or mixed CMBs (OR 3.479, 95% CI: 1.776-6.818, p < 0.001; OR 3.415, 95% CI: 1.863-6.258, p < 0.001). CONCLUSIONS: Urinary IgG was associated with the prevalence of D/I or mixed location CMBs in TIA or ischemic stroke patients. Our findings provide new insights into the association between urinary IgG and the distribution of CMBs.

Effects of monotherapy with a monoamine oxidase B inhibitor on motor symptoms in Parkinson's disease are dependent on frontal function.

BACKGROUND: Monotherapy with monoamine oxidase B (MAO-B) inhibitors enhances the level of endogenous dopamine in treatment for Parkinson's disease (PD) and provides some benefits. Certain neuropsychiatric functions are also regulated by central dopaminergic activity. AIM: To investigate the relationship of the efficacy of monotherapy with MAO-B inhibitors on motor symptoms in PD with baseline cognitive function. PATIENTS AND METHODS: Outcomes were examined for 27 consecutive drug-naïve PD patients who received initial treatment with a MAO-B inhibitor (selegiline: 11, rasagiline: 16). Selegiline was titrated to an optimal dose. The dose of rasagiline was fixed at 1 mg/day. Motor symptoms were assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III before treatment and after the efficacy reached a plateau within 19 weeks after drug initiation, and the % improvement in motor symptoms was calculated. Pre-treatment cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB). Correlations of % improvement in motor symptoms and baseline cognitive assessments were examined using Spearman correlation coefficients and multiple regression analysis. RESULTS: In all patients, the mean % improvement in motor symptoms was 46.5% (range 0-83.3%). Spearman correlation coefficients showed the % improvement in motor symptoms was correlated with FAB (r = 0.631, p < 0.001). In multiple regression analysis with patient background factors as independent variables, only FAB was associated with improvement in motor symptoms in the MAO-B group. CONCLUSION: Better FAB scores predict a significant improvement in motor symptoms with treatment with MAO-B inhibitors, suggesting high activity of endogenous dopamine.

Generalized myasthenia gravis patients infected with COVID-19 should continue eculizumab.

Eculizumab, a humanized monoclonal antibody, is a complement inhibitor indicated for refractory generalized myasthenia gravis (MG). However, there are limited data on the safety of eculizumab for MG during coronavirus disease 2019 (COVID-19) infection. We report a case in which eculizumab was continued for MG after contracting COVID-19, followed by a favorable outcome.

The association between urinary pentosidine levels and cognition in drug-naïve patients with Parkinson's disease.

Advanced glycation end products (AGEs) are suggested to play a potential role in the progression of Parkinson's disease (PD). The association between urinary levels of pentosidine, one of the best-characterized AGEs, and clinical conditions such as motor severity and cognition were investigated in patients with PD. Data on the clinical characteristics and urinary levels of pentosidine for 44 drug-naïve patients aged 60 years or older with PD were collected. The association between urinary pentosidine levels and severity of motor symptoms and cognition was analyzed using the Montreal Cognitive Assessment Scale (MoCA). Urinary pentosidine values increased with age (R2 = 0.286, p < 0.001) and were negatively correlated with the MoCA score (R2 = 0.255, p = 0.001). Urinary pentosidine levels were significantly correlated with age (r = 0.535, p < 0.001), Hoehn-Yahr stage (r = 0.340, p < 0.05), and total MoCA score (r = - 0.505, p < 0.001). Multiple linear regression analysis showed that older age (ß = 0.543; 95% confidence interval [CI] 0.300, 1.307; p = 0.003) was significantly associated with severity of motor symptoms, and that older age (ß = - 0.456; 95% CI - 0.287, - 0.054; p = 0.005) and urinary pentosidine levels (ß = - 0.311; 95% CI - 0.428, - 0.004; p = 0.046) were significantly associated with a lower MoCA score. Urinary pentosidine levels were significantly associated with lower cognition in drug-naïve PD patients. These findings have important clinical implications and suggest that pentosidine may be a potential marker for cognitive impairment in early PD.

Dynamic ultrasound findings in drinking and mastication steal syndrome; Case report.

Steal syndrome is a vascular disorder characterized by the inappropriate alterations of blood flow through adjacent collateral blood vessels to compensate for ischemia in organs with severely reduced or lost blood flow. The result may lead to dysfunction or ischemia of the end organs supplied by the collateral vessels. A 76-year-old man presented with a recurring, transient right-sided amaurosis that lasted about 30 min when drinking and mastication during meals. Carotid ultrasound and angiography showed severe stenosis of the right common carotid artery, and retrograde flow of the right external carotid artery via a collateral branch from the right vertebral artery. After drinking and mastication, steal syndrome from the right internal carotid artery to the external carotid artery were observed in real time by ultrasound. After percutaneous angioplasty for stenosis, the anastomosis from the vertebral artery to the external carotid artery, and the retrograde flow of the external carotid artery disappeared, and amaurosis improved during mastication and drinking. We found that drinking and mastication caused a phenomenon of blood theft from the internal carotid artery to the external carotid artery in common carotid artery stenosis. It is important to recognize the clinical presentation of these patients, because this condition is potentially reversible once identified with a proper evaluation and appropriate surgical intervention applied.

Middle Cerebral Artery Pulsatility Index Correlates with Prognosis and Diastolic Dysfunctions in Acute Ischemic Stroke.

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Communication-type smartphone application can contribute to reducing elapsed time to reperfusion therapy.

BACKGROUND AND OBJECTIVES: Communication-type medical smartphone applications enable text, neuroimaging, photos, and videos to be shared securely among the stroke team. Our aim was to investigate whether use of a smartphone application would shorten the duration from admission to reperfusion therapy in patients with hyper-acute ischemic stroke. METHODS: Enrolled were acute ischemic stroke patients who underwent reperfusion therapy (intravenous tissue plasminogen activator (IV t-PA) and mechanical thrombectomy (MT)) at our hospital between October 2012 and September 2018. We divided the patients into two groups based on the date of availability on smartphones of communication-type medical application: (1) Control group, conventional communication prior to September 2015, and (2) App group, communication via the smartphone app from October 2015 onwards. We compared door-to-image time (DIT), image-to-needle time (INT), door-to-needle time (DNT) for thrombolysis, and DIT, image-to-puncture time (IPT), and door-to-puncture time (DTP) for thrombectomy between the groups. RESULTS: We retrospectively enrolled 139 patients (68% male; median age, 69 years; median NIHSS score, 7) who were assigned into the App group (n = 86) and Control group (n = 53). Of the overall patients, 109 underwent IV t-PA (IV t-PA alone, 79 patients), and 63 underwent MT (MT alone, 30 patients), and 33 patients underwent combined IV t-PA and MT. There was no significant difference in DIT between the App and Control groups (23 min vs. 22 min, p = 0.493). DNT, DPT, INT, and IPT were significantly shorter in the App group than in the Control group (DNT, 62 min for the App group vs. 72 min for Control group, p = 0.038; INT, 42 vs. 48 min, p = 0.009; DPT, 106 vs. 129 min, p = 0.046; IPT, 89 vs. 117 min, p = 0.004). CONCLUSION: The present findings indicate that communication-type medical smartphone apps have potential for shortening the time elapsed between admission and reperfusion therapy, especially INT and IPT.

Face pareidolia is associated with right striatal dysfunction in drug-naïve patients with Parkinson's disease.

BACKGROUND AND AIM: Some patients with Parkinson's disease (PD) present with pareidolia, an illusion of a meaningless stimulus as a familiar object known to the observer. Since the striatum is associated with processing of visual information, we investigated correlations of pareidolia with motor symptoms and striatal dopaminergic function. METHOD: A noise pareidolia test, assessment of motor symptoms using MDS-UPDRS and 123I-Ioflupane SPECT were performed in 58 drug-naïve PD patients. A number of images in which a participant noticed an illusory face (number of illusory responses) were compared with motor assessment scores and uptake of 123I-ioflupane in the striatum. RESULTS: Of the 58 participants, 22 had at least one illusory response. Mean scores for MDS-UPDRS part III (p<0.05), rigidity (p<0.05), and rigidity on the left side of the body (p<0.01) in patients with pareidolia were significantly higher than those in patients without pareidolia. Uptake of 123I-ioflupane in the right caudate nucleus (p<0.05), anterior putamen (p<0.01), and posterior putamen (p<0.01) in patients with pareidolia was significantly lower than in patients without pareidolia. In the 22 patients with pareidolia, the number of illusory responses was significantly correlated with total scores for MDS-UPDRS part III (r=0.443, p<0.05) and subscores for bradykinesia (r=0.440, p<0.05) and bradykinesia on the left side of the body (r=0.564, p<0.01). The prevalence of pareidolia in left-dominant parkinsonism (16/30 patients) was higher than that in right-dominant parkinsonism (6/28 patients) (p<0.05 by chi-square test). CONCLUSION: Pareidolia in PD patients is associated with dysfunction in the right striatum.

Cerebral Microbleeds Load and Long-Term Outcomes in Minor Ischemic Stroke.

BACKGROUND AND PURPOSE: The association between the cerebral microbleed (CMB) count and outcomes in ischemic stroke has not been fully clarified. The aim of this study was to investigate the relationship between the CMBs count and functional outcomes in patients with a minor ischemic stroke treated with antiplatelet therapy METHODS: Non-cardiogenic minor ischemic stroke (NIHSS score < 4 on admission) patients who were treated with antiplatelet therapy were enrolled. The patients were divided into four groups based on the number of CMBs (absent, 1, 2-4, and > 4), and their clinical outcomes were compared. A poor outcome was defined as a modified Rankin scale (mRS) score of 3-6 90 days after symptom onset. Logistic regression analysis was performed to evaluate whether the CMBs count contributes to poor outcomes with well-known risk factors such as age, NIHSS score on admission, ischemic stroke recurrence, large artery atherosclerosis stroke subtype, and DWMHs. RESULTS: A total of 240 patients were enrolled, and their pre mRS scores were matched based on CMB presence. A higher burden of CMBs was linearly correlated with the incidence of poor outcomes (4% in the absent group, 8% in the 1 CMB group, 13% in the 2-4 CMB group, and 20% in the > 4 CMB group, P = 0.002). Multivariate logistic regression analysis showed that CMBs count was one of the independent factor associated with poor outcomes (odds ratio 1.07, 95% confidence interval 1.02-1.12, P = 0.003). CONCLUSION: The CMBs count contributes independently to poor outcomes in minor ischemic stroke patients treated with antiplatelet therapy.

Crossed Choreoathetosis Caused by Unilateral Thalamic Hemorrhage.

In general, involuntary movements after stroke are due to a disturbance in the unilateral cortico-basal ganglia loop and appear contralateral to stroke lesions. Crossed involuntary movements after unilateral stroke are very rare. We observed a case of crossed involuntary movements in the left upper limb and right lower limb after a right thalamic hemorrhage expanded to the right subthalamic nucleus. We considered a possible three-step theory as the basis of crossed choreoathetosis. This case informs our better understanding of the cortico-basal ganglia loop and involuntary movements after stroke.

Employment Status Prior to Ischemic Stroke and Weekly Variation of Stroke Onset.

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.

Convexity Subarachnoid Hemorrhage Accompanied by Hyperacute Ischemic Stroke.

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.

Differences in correlations of depression and anhedonia with cardiovascular sympathetic functions during a head-up tilt test in drug-naïve Parkinson's disease patients.

BACKGROUND: Depression is a symptom of Parkinson's disease (PD) and may be correlated with cardiovascular sympathetic function. Anhedonia is an element of depression, but these symptoms can emerge independently in PD. A correlation of anhedonia with cardiovascular sympathetic function has rarely been examined. OBJECTIVE: To compare correlations of depression and anhedonia with cardiovascular sympathetic function in drug-naive PD patients. METHODS: Assessments of depression (Self-rating Depression Scale; SDS), anhedonia (Snaith-Hamilton Pleasure Scale; SHAPS), myocardial 123I-MIBG (123I-meta-iodobenzylguanidine) scintigraphy (heart to mediastinum (H/M) ratios in early and delayed images), and head-up tilt test (HUT) up to 60° for 10 min were performed in 45 drug-naïve PD patients. During the HUT, blood pressure was measured every minute and the maximum decrease in systolic blood pressure (SBP) was determined. Plasma noradrenaline (NA) and arginine vasopressin (AVP) levels were examined at baseline and 10 min after tilt, with subsequent calculation of increases in plasma NA and AVP levels in this 10 min. Correlation coefficients were calculated among these assessment parameters. RESULTS: SDS significantly correlated with % maximum decrease in SBP (r = 0.344, p = 0.02), but not with H/M ratios in both images and increases in plasma NA and AVP levels. SHAPS did not correlate with the change in SBP, H/M ratios in both images, or plasma NA and AVP levels. CONCLUSION: Depression was correlated with the % maximum decrease in SBP during a 10-min HUT, but anhedonia did not show this relationship. This suggests that depression and anhedonia may have different pathophysiological backgrounds in drug-naïve PD patients.

Microbleeds of Lacunar Infarction and Middle Cerebral Artery Flow Velocity of Branch Atheromatous Disease Are Essential Factors of Stroke Etiology.

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.

Large but Nonstenotic Carotid Artery Plaque in Patients With a History of Embolic Stroke of Undetermined Source.

Background and Purpose- This study's objective is to determine if nonstenotic carotid plaque of <50% luminal narrowing predominantly develops ipsilateral rather than contralateral to the stroke site. 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 (<50%) is considerably more common when ipsilateral to the ESUS site than when contralateral to the ESUS site, especially in plaque with a thickness ≥2.6 mm. Large but nonstenotic carotid artery plaque is associated with anterior circulation ESUS.

The NAG scale: Noble Predictive Scale for Hematoma Expansion in Intracerebral Hemorrhage.

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.

YAMATO Study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy).

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.

Venous Stasis and Cerebrovascular Complications in Cerebral Venous Sinus Thrombosis.

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.

An In Vitro Assay for Sonothrombolysis Based on the Spectrophotometric Measurement of Clot Thickness.

OBJECTIVES: For improved thrombolysis therapy based on ultrasound irradiation, researchers and practitioners would strongly benefit from an easy and efficient in vitro assay system of thrombolysis activity involving irradiated ultrasound. For the present study, we designed a new in vitro sonothrombolysis assay system using a sheet-type clot. METHODS: We designed a cell for clot assay, and we confirmed that this clot cell did not significantly intervene in the acoustic field. Using human plasma, we made a sheet-type clot in the cell. Clot thicknesses at 100 points along 4 directions were measured photometrically at a rate of approximately 4 points/s. RESULTS: The sonothrombolysis effects at 13 levels of ultrasonic intensity were obtained with only one sheet-type clot. With this method, we used a clinically oriented probe at 0.7 and 0.3 W/cm2 to confirm that sonothrombolysis took place. CONCLUSIONS: We successfully established a new, easy, and efficient method for conducting in vitro sonothrombolysis assays. This method involves little intervention of either ultrasound reflection or standing waves in the clot cell. We believe that this new assay method is very useful for fundamental analyses of ultrasound's thrombolysis effects.