High pre-stroke CHADS2 score predicts unfavorable functional outcome in acute cardioembolic stroke patients prescribed oral anticoagulant therapy: A sub-analysis of the PASTA registry study.

BACKGROUND AND PURPOSE: The impact of CHADS2 score on outcome in patients with stroke taking an oral anticoagulant (OAC) has not yet been fully elucidated. We investigated the association between pre-stroke CHADS2 score and outcome at discharge in patients with acute cardioembolic (CE) stroke due to atrial fibrillation (AF) who were prescribed OAC. METHODS: The data of 548 OAC-treated patients with AF and CE stroke who were registered in the multicenter Prospective Analysis of Stroke patients Taking oral Anticoagulants (PASTA) study were analyzed. High CHADS2 score was defined as a pre-stroke CHADS2 score ≥2. Unfavorable outcome was defined as a modified Rankin scale (mRS) of 3-6. The impacts of pre-stroke CHADS2 score on outcome at discharge were evaluated using multiple logistic regression analysis. RESULT: A high CHADS2 score was found in 472/548 patients and unfavorable outcome was found in 330/548 patients. In patients with unfavorable outcome, age, male sex, pre-stroke CHADS2 score, initial National Institute Health Stroke Scale (NIHSS) score, and glucose level on admission were significantly higher, whereas creatinine clearance and body weight were significantly lower, than those with favorable outcome (each p < 0.001). Multivariate logistic regression analysis indicated that high CHADS2 score (OR 2.18, 95 %CI 1.08-4.42, p = 0.031), pre-stroke mRS (OR 2.21, 95 %CI 1.69-2.67, p < 0.001), and initial NIHSS score (OR 1.19, 95 %CI 1.17-1.24, p < 0.001) were independently associated with unfavorable outcome. CONCLUSION: Pre-stroke CHADS2 score was associated with poor outcome in patients with cardioembolic stroke due to AF, even in those taking OAC.

Fluid-Attenuated Inversion Recovery May Serve As a Tissue Clock in Patients Treated With Endovascular Thrombectomy.

Background and Purpose: We investigated whether the signal change on fluid-attenuated inversion recovery (FLAIR) can serve as a tissue clock that predicts the clinical outcome after endovascular thrombectomy (EVT), independently of the onset-to-admission time. Methods: Consecutive patients with acute stroke treated with EVT between September 2014 and December 2018 were enrolled. Based on the parenchymal signal change on FLAIR, patients were classified into FLAIR-negative and FLAIR-positive groups. The clinical characteristics, imaging findings, EVT parameters, and the intracranial hemorrhage defined as Heidelberg Bleeding Classification ≥1c hemorrhage (parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, and/or subdural hemorrhage) were compared between the 2 groups. A modified Rankin Scale score 0 to 1 at 3 months was considered to represent a good outcome. Results: Of the 227 patients with EVT during the study period, 140 patients (62%) were classified into the FLAIR-negative group and 87 (38%) were classified into the FLAIR-positive group. In the FLAIR-negative group, the patients were older (P=0.011), the onset-to-image time was shorter (P<0.001), the frequency of cardioembolic stroke was higher (P=0.006), and the rate of intravenous thrombolysis was higher (P<0.001) in comparison to the FLAIR-positive group. Although the rate of complete recanalization after EVT did not differ between the 2 groups (P=0.173), the frequency of both any-intracranial hemorrhage and Heidelberg Bleeding Classification ≥1c hemorrhage were higher in the FLAIR-positive group (P=0.004 and 0.011). At 3 months, the percentage of patients with a good outcome (FLAIR-negative, 41%; FLAIR-positive, 27%) was significantly related to the FLAIR signal change (P=0.047), while the onset-to-image time was not significant (P=0.271). A multivariate regression analysis showed that a FLAIR-negative status was independently associated with a good outcome (odds ratio, 2.10 [95% CI, 1.02­4.31], P=0.044). Conclusions: A FLAIR-negative status may predict the clinical outcome more accurately than the onset-to-admission time, which may support the role of FLAIR as a tissue clock.

Tokyo Metropolitan Stroke Emergency Medical Services for Interventional Stroke Treatment: The Tama-REgistry of Acute Thrombectomy (TREAT) Study.

OBJECTIVE: It is not clear how patients with large vessel occlusion (LVO) who have undergone mechanical thrombectomy (MT) were transported to hospitals by emergency medical services. Here, we describe the current status of the stroke delivery system in a large city. METHODS: We investigated data from 328 patients (male, n = 199; average age, 74.8 ± 12.9 years) who underwent MT at 12 facilities in the Tama area of Tokyo, between January 2015 and December 2017. The patients were classified according to the destination institution as Stroke A eligible (group A, n = 266 [8.2%]), Tertiary critical care center (group T; n = 35 [10.7%]), and other destinations such as emergency rooms (group O; n = 27 [8.2%]), and then reasons for using Emergency Medical Service (EMS) services and outcomes were compared among the groups. RESULTS: Rates of milder stroke, and middle cerebral artery occlusion were significantly higher in group A than T, whereas that of vertebral-basilar artery occlusion was significantly lower in group A than in groups T and O. The amount of elapsed time from door to picture (DTP) was significantly lower in group A. The time from onset to recanalization, as well as rates of successful recanalization and favorable outcomes (90-day modified Rankin scale 0-2) did not significantly differ regardless of destination. CONCLUSIONS: Most patients with LVO in the Tama area were categorized into group A. DTP was significantly lower in group A.

Changes in Whole-Blood microRNA Profiles during the Onset and Treatment Process of Cerebral Infarction: A Human Study.

Circulating miRNA species are promising symptom markers for various diseases, including cardiovascular disease. However, studies regarding their role in the treatment process are limited, especially concerning cerebral infarction. This study aimed to extract miRNA markers to investigate whether they reflect both onset and treatment process of cerebral infarction. A total of 22 patients (P-group) and 22 control subjects (C-group) were examined for their whole-blood miRNA profiles using DNA GeneChip™ miRNA 4.0 Array, with six patients examined after treatment (T-group). A total of 64 miRNAs were found to be differentially expressed between the C- and P-groups. Out of 64 miRNAs, the expression levels of two miRNAs correlated with hypertension. A total of 155 miRNAs were differentially expressed between the P- and T-groups. Five common miRNAs were found among the 64 and 155 miRNAs identified. Importantly, these common miRNAs were inversely regulated in each comparison (e.g., C < P > T), including miR-505-5p, which was previously reported to be upregulated in aortic stenosis patients. Our previous study using rat cerebral infarction models detected the downregulation of an apoptosis repressor, WDR26, which was repressed by one of the five miRNAs. Our results provide novel information regarding the miRNA-based diagnosis of cerebral infarction in humans. In particular, the five common miRNAs could be useful makers for the onset and the treatment process. Trial registration: This study was registered in the UMIN Clinical Trials Registry (UMIN000038321).

Decline in Hemoglobin during Hospitalization May Be Associated with Poor Outcome in Acute Stroke Patients.

BACKGROUND AND PURPOSE: Anemia upon hospital admission is a known predictor of poor functional outcomes in patients with acute cerebral infarction. However, it remains unclear whether reductions in hemoglobin levels during hospitalization influence stroke outcomes. We investigated the association between in-hospital decline in hemoglobin and poor outcomes. MATERIALS AND METHODS: We retrospectively analyzed data from 480 consecutive patients who had experienced acute cerebral infarction and presented without anemia between January 2012 and March 2015. Decline in hemoglobin was taken as the difference between hemoglobin levels upon admission and nadir hemoglobin. Poor outcome was defined as a modified Rankin Scale score 3-6. A multivariate analysis of the relationship between decline in hemoglobin and poor outcome at discharge was conducted for various patient characteristics. RESULTS: The mean hemoglobin level at admission was 14.3 ± 1.3 g/dL, whereas the mean nadir hemoglobin value was 13.1 ± 1.9 g/dL, with a mean decline in hemoglobin of 1.3 ± 1.5 g/dL. In patients with poor outcomes, mean decline in hemoglobin was significantly reduced to 3.1 g/dL (P < .001). The optimal cutoff decline in hemoglobin required to distinguish a poor outcome was 1.5 g/dL whereas the sensitivity and specificity were 62% and 82.3%, respectively, with an area under the curve of .77 (P < .0001). A decline in hemoglobin below 1.5 g/dL was found to be an independent predictor of poor outcome (odds ratio: 2.10; confidence interval: 1.10-3.99; P = .023). CONCLUSION: Decline in hemoglobin in patients hospitalized with acute stroke may be associated with poor outcome.

The Prevalence of and Factors Related to Vascular Hyperintensity on T1-Weighted Imaging in Acute Ischemic Stroke.

BACKGROUND: Thrombus visualization in patients with acute ischemic stroke has been detected and reported using various imaging modalities. T1-weighted imaging (T1-WI) can depict thrombi as hyperintense signals within vessels. Moreover, in addition to thrombi, T1-WI hyperintensities in arteries may suggest arterial dissection. However, the frequency of and factors related to the T1-hyperintense vessel sign (T1-HVS) are not fully known. The aim of this study was to clarify the prevalence of and related factors for the T1-HVS in patients with acute ischemic stroke. METHODS: From September 2014 through December 2015, consecutive acute ischemic stroke patients who were admitted to our stroke unit within 7 days from symptom onset were retrospectively recruited from the prospective registry. A T1-HVS was defined as the presence of a hyperintense signal, with intensity higher than surrounding brain, within the vessel lumen. Moreover, T1-HVSs were separated into filled T1-HVSs (hyperintensity fills whole vessel lumen) and non-filled T1-HVSs. The frequency of the T1-HVS and the timing of emersion and the relationship between the presence of the T1-HVS and arterial occlusion were assessed. RESULTS: A total of 399 patients (139 women; median age 73 years; National Institutes of Health Stroke Scale score 3) were enrolled in the present study. Of these, 327 (82%) patients had T1-WI on admission. Two hundred and sixty-seven (67%) subjects had at least one follow-up T1-WI (median 6 days after admission), and 134 (34%) cases had ≥2 follow-up T1-WI examinations. The T1-HVS was observed in 18 patients during admission; therefore, the frequency of the T1-HVS in acute ischemic stroke patients was 4.5% (95% CI 2.5-6.5%). All but one (94%) of the T1-HVSs were first observed on follow-up imaging, and the median number of days from onset to T1-HVS appearance was 9. For patients having initial major artery occlusion and follow-up MRI (n = 95), sensitivity and specificity of the T1-HVS for persistent arterial occlusion on follow-up MR angiography were 22 and 100%, respectively. T1-HVS persisted for a few months and then normalized. Although there were no significant differences between filled and non-filled T1-HVS, more patients with non-filled T1-HVS had arterial dissection (43%) than those with filled T1-HVS (9%, p = 0.245). CONCLUSION: The T1-HVS was observed in 4.5% of acute ischemic stroke patients. T1-HVSs appeared in the subacute phase in arteries with persistent occlusion and remained for a few months.

Gene Expression Analysis of the Effect of Ischemic Infarction in Whole Blood.

Given the abundance of stroke patients and deaths from stroke worldwide, many studies concerning the aftermath of stroke are being carried out. To reveal the precise effect of ischemic infarction, we conducted a comprehensive gene expression analysis. Alongside a middle cerebral artery occlusion (MCAO) Sprague-Dawley rat model, we used a group undergoing sham surgery for comparison, which was the same as MCAO surgery but without blood vessel occlusion. Subsequently, infarction of the brains of MCAO-treated rats occurred, but did not occur in the sham-treated rats. Using whole blood, we carried out DNA microarray analysis, revealing the gene expression alterations caused by stroke. Downregulation of immune pathways and cluster of differentiation (CD) molecules indicated immunodepression. By conducting miRNA microarray analysis, we extracted seven miRNAs as significantly regulated: miR-107-5p, miR-383-5p, miR-24-1-5p, mir-191b, miR-196b-5p, and miR-3552 were upregulated, and mir-194-1 was downregulated. Among these seven miRNAs, three had one target mRNA each that was extracted as differentially expressed, and the expression levels of all pairs were inversely correlated. This indicates the occurrence of miRNA-mRNA regulatory systems in blood: between miR-107-5p and H2A histone family member Z (H2afz), miR-196b-5p and protein tyrosine phosphatase receptor type C (Ptprc), and miR-3552 and serine/arginine-rich splicing factor 2 (Srsf2). Moreover, six miRNAs had matching human miRNAs with similar sequences, which are potential human stroke biomarkers.

Efficiency of the Penumbra 5MAX ACE Reperfusion Catheter in Acute Ischemic Stroke Patients.

OBJECTIVE: This study was performed to investigate whether the Penumbra 5MAX ACE is superior to other Penumbra systems. MATERIALS AND METHODS: We performed a retrospective, single center analysis of patients with acute ischemic stroke with occlusion of the internal carotid artery or middle cerebral artery (M1 segment) who underwent endovascular therapy using a Penumbra system. The reperfusion success rate, puncture-to-revascularization time, and number of passes were assessed. Multivariate regression analysis was conducted to evaluate independent factors related to revascularization within 60 minutes. Successful revascularization was defined by a thrombolysis in cerebral infarction score ≥2b. RESULTS: The Penumbra 5MAX ACE was used in 24 of the 40 patients (60%). Although the revascularization success rate was similar between patient groups (P = .229), the number of passes was significantly lower (1.5 ± .8 versus 2.6 ± 1.3, P = .006) and the puncture-to-revascularization time was shorter (50 ± 26 minutes versus 116 ± 69 minutes, P = .002) in patients treated with the Penumbra 5MAX ACE. The Penumbra 5MAX ACE was identified as an independent factor for early revascularization (odds ratio, 5.80; P = .041). Among patients with a premorbid modified Rankin Scale score of 0-1, a modified Rankin Scale score of 0-2 at 3 months was observed in 15 of the 19 patients (79%) treated with the Penumbra 5MAX ACE and in 8 of the 16 (50%) who were not (P = .072). CONCLUSION: Acute revascularization therapy using the Penumbra 5MAX ACE can achieve rapid successful recanalization and tend to improve clinical outcomes.

Multiple Cerebral Infarctions in a Patient with Adenomyosis on Hormone Replacement Therapy: A Case Report.

A 59-year-old woman was admitted to our hospital because of repeated episodes of bilateral hand weakness. She had a 10-year history of combined estrogen-progestin therapy for menopausal symptoms. Magnetic resonance imaging on admission showed multiple hyperintense lesions in bilateral cerebral and cerebellar cortices on diffusion-weighted imaging. Transesophageal echocardiography showed thrombus formation on the aortic valve and moderate aortic insufficiency. Laboratory test demonstrated elevated CA125 (334.8 U/mL) and D-dimer (7.0 µg/mL) levels. Trousseau's syndrome (cancer-related hypercoagulation) was considered, but various examinations showed only uterine adenomyosis and no evidence of cancer. Multiple cerebral infarctions were considered to be caused by Trousseau's syndrome-like condition associated with uterine adenomyosis. CA125 and coagulation markers should be measured in adenomyosis patients treated with hormone replacement therapy, because a mucinous tumor and coagulation markers may be good markers for the risk of thromboembolism in such patients.

Spontaneous Bilateral Cervical Internal Carotid and Vertebral Artery Dissection in a Japanese Patient without Collagen Vascular Disease with Special Reference to Single-Nucleotide Polymorphisms.

Spontaneous cervical artery dissection (sCAD) is a major cause of ischemic stroke in young adults. Frequently, sCAD involves multiple neck arteries, accounting for 13%-28% of the total sCAD cases. However, little is known about factors related to multiple sCAD. In this case, a 52-year-old man was admitted due to headache without aura. There was a personal history of migraine with aura and a family history of similar symptoms. The patient's younger brother had a left vertebral artery (VA) dissecting aneurysm and underwent endovascular occlusion of his parent artery at the age of 48. Magnetic resonance imaging of our admitted patient showed hyperintensities in the right internal carotid artery (ICA) without acute infarction, and magnetic resonance angiography revealed a narrowing of the right ICA. Angiography was then performed, which showed a trace of dissection of the left ICA and both VAs as well as the right ICA. The patient did not fulfill any major criteria of collagen vascular disease such as Ehlers-Danlos syndrome type IV or Loeys-Dietz syndrome. The data in our patient are quite similar to those reported in patients with single-nucleotide polymorphism (SNP) of PHACTR1. Obtaining the patient's informed consent, we analyzed a common SNP variation in the rs9349379[G] allele (PHACTR1), which has been reported to be associated with a lower risk of sCAD.

Thrombolysis, Complete Recanalization, Diffusion Reversal, and Luxury Perfusion in Hyperacute Stroke.

A 59-year old man was admitted to our stroke care unit 1.8 hours after onset of cardioembolic stroke. Administration of issue-plasminogen activator achieved complete recanalization, and his lesion on diffusion-weighted imaging (DWI) disappeared and single photon emission computed tomography showed luxury perfusion. DWI reversal and luxury perfusion were sometimes observed in hyperacute stroke patients, especially timely reperfusion was achieved. However, the relationships between DWI reversal and luxury perfusion were not well known. Transient DWI reversal may be associated with luxury perfusion in patients treated with t-PA, via early complete recanalization achieved by thrombolysis.

Successful treatment of cerebral venous thrombosis associated with ulcerative colitis.

Thromboembolic complications, such as deep venous thrombosis and pulmonary embolism, are well described in patients with inflammatory bowel disease, but cerebral venous thrombosis (CVT) is a rare but potentially devastating complication. The authors describe the case of a 36-year-old Japanese man presenting with CVT associated with ulcerative colitis (UC) that was successfully treated with a combination of continuous anticoagulant and pulse steroid therapy. Our observations suggest that aggressive therapy for inducing acute UC remission is vitally important for CVT associated with UC.

Safety of recanalization therapy in patients with acute ischemic stroke on direct oral anticoagulants: A sub-analysis of PASTA registry study.

BACKGROUND: The safety of intravenous recombinant tissue plasminogen activator (rtPA) and mechanical thrombectomy (MT) in patients treated with direct oral anticoagulants (DOACs) before stroke has not been fully investigated. Therefore, we aimed to investigate the safety of recanalization therapy in patients receiving DOACs. METHODS: We assessed data from a prospective multicenter registry of patients with stroke, including those with acute ischemic stroke (AIS) treated with rtPA and/or MT who were administered DOACs. We evaluated the safety of recanalization considering the DOACs dosage and interval between the last DOAC intake and recanalization. RESULTS: The final analysis included 108 patients (women, n = 54; median age, 81 years; DOAC overdose, n = 7; appropriate dose, n = 74; and inappropriate low dose, n = 27). The rate of any ICH differed significantly among overdose-, appropriate dose-, and inappropriate-low dose DOACs groups (71.4, 23.0, and 33.3%, respectively; P = 0.0121), whereas no significant difference was observed in respect of symptomatic ICH (P = 0.6895). Multivariate analysis showed that the National Institutes of Health Stroke Scale score on admission (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.01-1.11; P = 0.0267) and overdose-DOAC (OR: 8.40, 95% CI: 1.24-56.88; P = 0.0291) were independently associated with any ICH. No relationship was observed between the timing of the last DOAC intake and occurrence of ICH in patients treated with rtPA and/or MT (all P > 0.05). CONCLUSION: Recanalization therapy during DOAC treatment may be safe in selected patients with AIS, if it is performed >4 h after the last DOAC intake and the patient is not overdosed with DOACs. REGISTRATION: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034958.

Vitamin K antagonists but not non-vitamin K antagonists in addition on antiplatelet therapy should be associated with increase of hematoma volume and mortality in patients with intracerebral hemorrhage: A sub-analysis of PASTA registry study.

BACKGROUND AND PURPOSE: Prior concomitant use of vitamin K antagonists (VKAs) and antiplatelet (AP) therapy increase the hematoma volume and mortality compared with VKA monotherapy in patients with intracranial hemorrhage (ICH). However, the prior concomitant use of non-vitamin K oral antagonists (NOACs) and AP has not been clarified. METHODS: We conducted a PASTA registry study, which was an observational, multicenter, registry of 1043 patients with stroke receiving oral anticoagulants (OACs) in Japan. In the present study, ICH from the PASTA registry was used to analyze the clinical characteristics including mortality among the four groups (NOAC, VKA, NOAC and AP, and VKA and AP) using univariate and multivariate analyses. RESULTS: Among the 216 patients with ICH, 118 (54.6%), 27 (12.5%), 55 (25.5%), 16 (7.4%) were taking NOAC monotherapy, NOAC and AP, VKA, and VKA and AP, respectively. In-hospital mortality rates were the highest in VKA and AP (31.3%) than in NOACs (11.9%), NOACs and AP (7.4%), and VKA (7.3%). Multivariate logistic regression analysis demonstrated that the concomitant use of VKA and AP (odds ratio [OR], 20.57; 95% confidence interval [CI], 1.75-241.75, p = 0.0162), initial National Institutes of Health Stroke Scale score (OR, 1.21; 95%CI, 1.10-1.37, p < 0.0001), hematoma volume (OR, 1.41; 95%CI, 1.10-1.90, p = 0.066), and systolic blood pressure (OR, 1.31; 95%CI, 1.00-1.75, p = 0.0422) were independently associated with in-hospital mortality. CONCLUSIONS: Although VKA in addition to AP therapy could increase the in-hospital mortality, NOAC and AP did not increase the hematoma volume, stroke severity, or mortality compared to NOAC monotherapy.

Sustained atrial fibrillation is related to a higher severity of stroke in patients taking direct oral anticoagulants.

BACKGROUND: Atrial fibrillation (AF) includes paroxysmal and sustained (persistent or permanent) AF, and both forms are considered risk factors for ischemic stroke. This study aimed to investigate the differences in stroke severity at admission between patients with paroxysmal AF and sustained AF when treated with direct oral anticoagulants (DOACs). METHODS: Using data from DOAC-treated 300 nonvalvular patients with AF and acute anterior circulation stroke who were registered in the Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants study, patients were divided into two groups, namely, paroxysmal AF and sustained AF. We compared the clinical characteristics between the two groups and determined the effect of these two types of AF on stroke severity on admission. RESULTS: Of 300 patients, 246 (males, n = 149; median age, 80 years) and 54 (males, n = 32; median age, 78 years) were assigned to the sustained AF and paroxysmal AF groups, respectively. The sustained AF group had a higher proportion of severe stroke (National Institutes of Health Stroke Scale score, >20) on admission (22.0% vs. 5.7%, p = 0.006) and internal carotid artery occlusion (11.4% vs. 1.9%, p = 0.03) compared to the paroxysmal AF group. Multivariate analysis showed that sustained AF was independently associated with severe stroke on admission (odds ratio 4.31, 95% confidence interval 1.24-15.0, p = 0.02). CONCLUSIONS: Sustained AF was associated with a higher severity of stroke accompanied with major vessel occlusion than paroxysmal AF, even prior to DOACs treatment. Registration https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034958.

Prior direct oral anticoagulant dosage and outcomes in patients with acute ischemic stroke and non-valvular atrial fibrillation: A sub-analysis of PASTA registry study.

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Selecting a low dose DOAC might be associated with poor functional outcomes in patients without renal dysfunction.

Characteristics of Ischemic Versus Hemorrhagic Stroke in Patients Receiving Oral Anticoagulants: Results of the PASTA Study.

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 p>0.05), between IS/TIA and ICH among both NOAC and VKA users. Cerebral microbleeds (CMBs) [odds ratio (OR), 4.77; p<0.0001] 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; p<0.0001) 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.

Nicergoline increases serum substance P levels in patients with an ischaemic stroke.

BACKGROUND: Aspiration pneumonia is one of the most important complications following ischaemic stroke, and a leading cause of mortality in stroke patients. This is particularly prevalent in patients with involvement of the basal ganglia, which may be due to impaired neurotransmission through lack of production of substance P. METHODS: Consecutive patients in the chronic stage, 1-3 months after cerebral ischaemic infarction, were assessed for basal ganglia involvement by magnetic resonance imaging. The patients were randomised to 4 weeks of treatment with (n = 25) or without (n = 25) nicergoline (15 mg t.i.d.). Serum concentration of substance P was measured by radioimmunoassay. RESULTS: At entry to the study, mean concentration of substance P was significantly (p < 0.001) lower in patients with bilateral basal ganglia lesions than in patients with no or unilateral basal ganglia involvement. Nicergoline administration caused a significant (p = 0.021) increase from baseline in mean substance P concentration. No significant change was seen in the nicergoline-untreated patients (p = 0.626). Among the patients who received nicergoline, 11 patients had bilateral basal ganglia involvement and there was no significant mean change in substance P in these patients, whereas there was a significant increase (p = 0.032) in the 14 nicergoline-treated patients with no or unilateral basal ganglia involvement. CONCLUSIONS: The present study suggests a possible effect of nicergoline to increase substance P level in ischaemic stroke patients with partial damage to basal ganglia, who have a decreased swallowing response and consequent risk of aspiration pneumonia. Further trials of nicergoline treatment in patients at risk for aspiration pneumonia are warranted.

Reducing door-to-reperfusion time in acute stroke endovascular therapy using magnetic resonance imaging as a screening modality.

BACKGROUND: The feasibility of performing MRI first for patients with suspected hyperacute stroke in real-world practice has not been fully examined. Moreover, most past studies of reducing door-to-reperfusion time (DRT) in endovascular treatment (EVT) were conducted using CT. The aim of this study was to evaluate the feasibility of an MRI-first policy and to examine the effects of a quality improvement (QI) process for reducing DRT using MRI. METHODS: From January 2013 to December 2018, consecutive patients with acute stroke who came to hospital directly and were treated with emergent EVT were prospectively enrolled into the present study. In principle, MRI was performed first for patients with suspected acute stroke. A step-by-step QI process for decreasing DRT was adopted during this period. Time metrics for EVT were compared between specific time periods. RESULTS: A total of 180 patients (71 women; median age 76 years (range 69-64); National Institutes of Health Stroke Scale score 17 (range 10-23)) were included in the present study. More patients in the late phase were managed with the MRI-first policy (p<0.001). DRT (199 min in Phase 1, 135 min in Phase 2, 129 min in Phase 3, and 121 min in Phase 4, p<0.001) was significantly reduced across the phases. The percentage of patients with DRT <120 min increased significantly across time periods (p<0.001). Symptomatic intracerebral hemorrhage did not increase across phases (p=0.575). CONCLUSION: An MRI-first policy was feasible, and DRT decreased considerably with a step-by-step QI process. This process may be applicable to other hospitals.

HTRA1-Related Cerebral Small Vessel Disease: A Review of the Literature.

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is clinically characterized by early-onset dementia, stroke, spondylosis deformans, and alopecia. In CARASIL cases, brain magnetic resonance imaging reveals severe white matter hyperintensities (WMHs), lacunar infarctions, and microbleeds. CARASIL is caused by a homozygous mutation in high-temperature requirement A serine peptidase 1 (HTRA1). Recently, it was reported that several heterozygous mutations in HTRA1 also cause cerebral small vessel disease (CSVD). Although patients with heterozygous HTRA1-related CSVD (symptomatic carriers) are reported to have a milder form of CARASIL, little is known about the clinical and genetic differences between the two diseases. Given this gap in the literature, we collected clinical information on HTRA1-related CSVD from a review of the literature to help clarify the differences between symptomatic carriers and CARASIL and the features of both diseases. Forty-six symptomatic carriers and 28 patients with CARASIL were investigated. Twenty-eight mutations in symptomatic carriers and 22 mutations in CARASIL were identified. Missense mutations in symptomatic carriers are more frequently identified in the linker or loop 3 (L3)/loop D (LD) domains, which are critical sites in activating protease activity. The ages at onset of neurological symptoms/signs were significantly higher in symptomatic carriers than in CARASIL, and the frequency of characteristic extraneurological findings and confluent WMHs were significantly higher in CARASIL than in symptomatic carriers. As previously reported, heterozygous HTRA1-related CSVD has a milder clinical presentation of CARASIL. It seems that haploinsufficiency can cause CSVD among symptomatic carriers according to the several patients with heterozygous nonsense/frameshift mutations. However, the differing locations of mutations found in the two diseases indicate that distinct molecular mechanisms influence the development of CSVD in patients with HTRA1-related CSVD. These findings further support continued careful examination of the pathogenicity of mutations located outside the linker or LD/L3 domain in symptomatic carriers.