Clinical impact of body mass index on outcomes of ischemic and hemorrhagic strokes.

BACKGROUND AND AIM: To investigate the prognostic implication of body mass index (BMI) on clinical outcomes after acute ischemic and hemorrhagic stroke. METHODS: The subjects of the study included adult patients with available baseline body weight and height data who had suffered an acute stroke and were registered in the Japan Stroke Data Bank-a hospital-based, multicenter stroke registration database-between January 2006 and December 2020. The outcome measures included unfavorable outcomes defined as a modified Rankin Scale (mRS) score of 5-6 and favorable outcomes (mRS 0-2) at discharge, and in-hospital mortality. Mixed effects logistic regression analysis was conducted to determine the relationship between BMI categories (underweight, normal weight, overweight, class I obesity, class II obesity; <18.5, 18.5-23.0, 23.0-25.0, 25-30, ⩾30 kg/m2) and the outcomes, after adjustment for covariates. RESULTS: A total of 56,230 patients were assigned to one of the following groups: ischemic stroke (IS, n = 43,668), intracerebral hemorrhage (ICH, n = 9741), and subarachnoid hemorrhage (SAH, n = 2821). In the IS group, being underweight was associated with an increased likelihood of unfavorable outcomes (odds ratio, 1.47 (95% confidence interval (CI):1.31-1.65)) and in-hospital mortality (1.55 (1.31-1.83)) compared to outcomes in those with normal weight. Being overweight was associated with an increased likelihood of favorable outcomes (1.09 (1.01-1.18)). Similar associations were observed between underweight and these outcomes in specific IS subtypes (cardioembolic stroke, large artery stroke, and small-vessel occlusion). Patients with a BMI ⩾30.0 kg/m2 was associated with an increased likelihood of unfavorable outcomes (1.44 (1.01-2.17)) and in-hospital mortality (2.42 (1.26-4.65)) in large artery stroke. In patients with ICH, but not those with SAH, being underweight was associated with an increased likelihood of unfavorable outcomes (1.41 (1.01-1.99)). CONCLUSIONS: BMI substantially impacts functional outcomes following IS and ICH. Lower BMI consistently affected post-stroke disability and mortality, while higher BMI values similarly affected these outcomes after large artery stroke.

High brain natriuretic peptide level is associated with severe stroke in patients taking oral anticoagulants: A sub-analysis of the PASTA registry study.

BACKGROUND: Brain natriuretic peptides (BNP) are an important diagnostic and prognostic marker in patients with heart failure. However, the relationship between BNP levels and stroke severity in patients with atrial fibrillation (AF) remains unelucidated. In this study, we aimed to investigate the association between stroke severity at admission and BNP levels. METHODS: In this prospective observational study, we used data from 513 patients with AF and acute ischemic stroke treated with oral anticoagulants (OAC) registered in the Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants study. The patients were divided into two groups: high-BNP (≥200 pg/mL) and low-BNP level (<200 pg/mL) groups. We compared the clinical characteristics between the two groups and determined the effect of BNP levels on stroke severity on admission. RESULTS: Among the 513 enrolled patients, 248 (females, n = 30; median age, 82 years) and 265 (females, n = 76; median age, 71 years) were assigned to the high- and low-BNP level groups, respectively. The high-BNP level group had a higher proportion of patients with severe stroke (National Institutes of Health Stroke Scale score, ≥10) on admission (49.2% vs. 32.8%, p = 0.002) and major vessel occlusion (57.5% vs. 39.2%, p < 0.0001) than that had by the low-BNP level group. Multivariate analysis showed that high BNP level was independently associated with severe stroke on admission (odds ratio 1.07, 95% confidence interval 1.00-1.15; p = 0.0478). CONCLUSIONS: High BNP level compared with low BNP level was associated with severe stroke and major vessel occlusion, even before OAC treatment.

Temporal Changes in Cerebral Blood Flow during Migraine with Aura of Alternating Left and Right Homonymous Hemianopsia.

A 16-year-old boy presented with sudden left homonymous hemianopsia followed by right ocular and occipital pain. Arterial spin labeling (ASL), a non-contrast magnetic resonance imaging technique used to evaluate perfusion, showed a decrease in cerebral blood flow in the right occipital lobe. Three hours after admission, the patient experienced right homonymous hemianopsia and ocular-to-occipital pain on the contralateral side. ASL revealed a decreased cerebral blood flow in the left occipital lobe. We ultimately diagnosed the patient with first-time migraine with aura, in which cortical spreading depression was visualized as decreased cerebral blood flow using ASL.

Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes with Alteplase at 0.6 mg/kg in Clinical Practice: THAWS2 Study.

INTRODUCTION: The aim of this study was to determine the safety and efficacy of intravenous (IV) alteplase at 0.6 mg/kg for patients with acute wake-up or unclear-onset strokes in clinical practice. METHODS: This multicenter observational study enrolled acute ischemic stroke patients with last-known-well time >4.5 h who had mismatch between DWI and FLAIR and were treated with IV alteplase. The safety outcomes were symptomatic intracranial hemorrhage (sICH) after thrombolysis, all-cause deaths, and all adverse events. The efficacy outcomes were favorable outcome defined as an mRS score of 0-1 or recovery to the same mRS score as the premorbid score, complete independence defined as an mRS score of 0-1 at 90 days, and change in NIHSS at 24 h from baseline. RESULTS: Sixty-six patients (35 females; mean age, 74 ± 11 years; premorbid complete independence, 54 [82%]; median NIHSS on admission, 11) were enrolled at 15 hospitals. Two patients (3%) had sICH. Median NIHSS changed from 11 (IQR, 6.75-16.25) at baseline to 5 (3-12.25) at 24 h after alteplase initiation (change, -4.8 ± 8.1). At discharge, 31 patients (47%) had favorable outcome and 29 (44%) had complete independence. None died within 90 days. Twenty-three (35%) also underwent mechanical thrombectomy (no sICH, NIHSS change of -8.5 ± 7.3), of whom 11 (48%) were completely independent at discharge. CONCLUSIONS: In real-world clinical practice, IV alteplase for unclear-onset stroke patients with DWI-FLAIR mismatch provided safe and efficacious outcomes comparable to those in previous trials. Additional mechanical thrombectomy was performed safely in them.

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.

Cerebral Small Vessel Disease Burden for Bleeding Risk during Antithrombotic Therapy: Bleeding with Antithrombotic Therapy 2 Study.

OBJECTIVE: This study was undertaken to determine the excess risk of antithrombotic-related bleeding due to cerebral small vessel disease (SVD) burden. METHODS: In this observational, prospective cohort study, patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were enrolled from 52 hospitals across Japan between 2016 and 2019. Baseline multimodal magnetic resonance imaging acquired under prespecified conditions was assessed by a central diagnostic radiology committee to calculate total SVD score. The primary outcome was major bleeding. Secondary outcomes included bleeding at each site and ischemic events. RESULTS: Of the analyzed 5,250 patients (1,736 women; median age = 73 years, 9,933 patient-years of follow-up), antiplatelets and anticoagulants were administered at baseline in 3,948 and 1,565, respectively. Median SVD score was 2 (interquartile range = 1-3). Incidence rate of major bleeding was 0.39 (per 100 patinet-years) in score 0, 0.56 in score 1, 0.91 in score 2, 1.35 in score 3, and 2.24 in score 4 (adjusted hazard ratio [aHR] for score 4 vs 0 = 5.47, 95% confidence interval [CI] = 2.26-13.23), that of intracranial hemorrhage was 0.11, 0.33, 0.58, 0.99, and 1.06, respectively (aHR = 9.29, 95% CI = 1.99-43.35), and that of ischemic event was 1.82, 2.27, 3.04, 3.91, and 4.07, respectively (aHR = 1.76, 95% CI = 1.08-2.86). In addition, extracranial major bleeding (aHR = 3.43, 95% CI = 1.13-10.38) and gastrointestinal bleeding (aHR = 2.54, 95% CI = 1.02-6.35) significantly increased in SVD score 4 compared to score 0. INTERPRETATION: Total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting the broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy. ANN NEUROL 2024;95:774-787.

Resumption of oral anticoagulation in patients with non-valvular atrial fibrillation after intracerebral hemorrhage: A sub-analysis of the PASTA registry study.

PURPOSE: To investigate the rate and timing of oral anticoagulant (OAC) resumption and its safety in patients after intracerebral hemorrhage (ICH) in current clinical practice in Japan. METHODS: We conducted a sub-analysis of the PASTA registry, an observational, multicenter registry of 1043 patients with stroke receiving OACs in Japan, by including patients with ICH on OAC treatment for non-valvular atrial fibrillation (NVAF). The clinical characteristics of the patients in the resumption and non-resumption groups, rate and timing of OAC resumption, its safety, and switching of OACs after ICH were investigated. RESULTS: Of the 160 patients (women, n = 52; median age, 77 years) included, OACs were resumed in 108 (68%) at a median of 7 days (interquartile range, 4-11) after acute ICH onset. The non-resumption group had higher rates of hematoma expansion (21.2% vs. 7.4%; P = 0.0118) and modified Rankin Scale (mRS) scores at discharge (4 (Suda et al., 2019; Steiner et al., 2014 [3, 4]) vs. 4 (Suda et al., 2019; Steiner et al., 2014; Pasquini et al., 2014 [3-5]); P = 0.0302}. The resumption rate in the mRS 0-4 group was higher than that in the mRS 5 group (75.2% vs. 46.5%; P = 0.00006). The number of days to resumption after ICH onset was longer in the mRS 5 than that in the mRS 0-4 group (median 12 days vs. 7 days, P = 0.0065). There were no significant differences in new-onset ICH, symptomatic hematoma expansion, or gastrointestinal bleeding between groups (P > 0.05). CONCLUSIONS: Early resumption of OAC for NVAF in patients after ICH appeared to be safe. Expected functional outcomes at discharge were associated with OAC resumption and with the timing of resumption. REGISTRATION: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034958.

Association between Carotid Bifurcation Angle and Vulnerable Plaque Volume Using Black Blood Magnetic Resonance Imaging.

The morphology of the internal carotid artery (ICA) bifurcation is increasingly being recognized as the cause of atherosclerosis and vulnerable plaque leading to cerebral infarction. In this study, we investigated the relationship between carotid bifurcation angle and carotid plaque volume evaluated using black blood magnetic resonance imaging (BB-MRI). Among the 90 patients who underwent revascularization for atherosclerotic symptomatic carotid stenosis between April 2016 and October 2022 using BB-MRI, carotid plaque was evaluated in 57 patients. Relative overall signal intensity (roSI) was defined as the signal intensity of the plaque on T1-weighted images relative to the signal intensity of the sternocleidomastoid muscle in the same slice as the common carotid bifurcation. Regions showing roSI ≥ 1.0 were defined as plaque, and the plaque volume and relative plaque volume were measured from roSI ≥1.0 to ≥2.0 in 0.1 increments. We calculated the angles between the common carotid artery (CCA) and the ICA and between the CCA and the external carotid artery (ECA) on magnetic resonance angiography. We classified two groups according to carotid bifurcation angles based on the ICA angle: Group A = <35° and Group B = ≥35°. Compared with Group A (n = 42), Group B (n = 15) showed a greater relative plaque volume between roSI ≥ 1.3 and roSI ≥ 1.5. A significant correlation was identified between relative plaque volume with roSI ≥ 1.4 and ICA angle (p = 0.049). Vulnerable plaque was significantly more frequent in the group with an ICA angle of ≥35. Moreover, the ICA angle was significantly greater in patients with a roSI of ≥1.4.

JAK2 V617F Mutation and Large Cerebral Artery Disease in Patients with Myeloproliferative Neoplasms.

AIM: The aim of the present study was to clarify the association between the Janus kinase 2 (JAK2) V617F mutation and large cerebral artery disease (LCAD) in patients with myeloproliferative neoplasms (MPNs). METHODS: We retrospectively analysed patients diagnosed with MPNs between June 1992 and June 2022 who underwent brain magnetic resonance imaging. LCAD was defined as extracranial or intracranial large artery stenosis (≥ 50%) or occlusion on magnetic resonance angiography. RESULTS: A total of 86 patients (47 males; median age, 69 years old) were enrolled in this study. JAK2 V617F mutation was detected in 63 (73.3%) patients and LCAD in 35 (40.7%) patients. Univariate analysis showed that history of ischaemic stroke (LCAD, 62.9% vs. non-LCAD, 11.8%; P＜0.001), JAK2 V617F mutation (91.4% vs. 60.8%, P=0.002), and age ≥ 60 years (85.7% vs. 60.8%, P=0.016) were significantly associated with LCAD. Multiple logistic regression analysis showed that, in addition to ischaemic stroke, age ≥ 60 years and diabetes mellitus, JAK2 V617F mutation (odds ratio 29.2, 95% confidence interval 1.2-709.8, P=0.038) was independently associated with LCAD. LCAD was frequently observed in the intracranial carotid (14/35, 40.0%) and middle cerebral (13/35, 37.1%) arteries. CONCLUSIONS: This study revealed a significant association between the JAK2 V617F mutation and LCAD in patients with MPNs. This suggests that the JAK2 V617F mutation may promote cerebrovascular atherosclerosis and could be very important in determining therapeutic strategies for patients with not only JAK2 V617F-mutated MPNs but also LCAD-related stroke.

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.

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.

Heterogeneity of Stroke in Patients with Systemic Lupus Erythematosus.

Objective The underlying pathophysiology varies according to stroke subtype. However, stroke heterogeneity among patients with systemic lupus erythematosus (SLE) remains unstudied. We hypothesized that the contribution of SLE to stroke might vary according to its subtype and investigated the associations of SLE and various stroke subtypes. Methods Diagnostic codes and electronic medical records were used to identify 70 patients with SLE who developed acute cerebral infarction or intracerebral hemorrhaging at four tertiary referral hospitals between 2008 and 2018. Intracerebral hemorrhaging was classified as lobar or deep, while cerebral infarction was classified according to the SSS-TOAST criteria. Physician notes were used to identify SLE activity, and their prevalences were compared among stroke subtypes. Outcomes were collected from the patients' medical records. Results The most common stroke subtype in patients with SLE was that of undetermined causes (31%), followed by small artery occlusion (16%), cardioaortic embolism (13%), other causes (11%), lobar hemorrhaging (10%), deep hemorrhaging (10%), and large artery atherosclerosis (9%). Stroke onset occurred during a period of high SLE activity in 21 patients (30%). The proportion of patients with high SLE activity varied according to stroke subtype (p=0.039) and was highest for cerebral infarction with undetermined causes. Stroke recurrence or death was observed in 40% of patients within 5 years after the initial stroke onset. Conclusion The contributions of SLE to stroke varied significantly according to the stroke subtype. Given the unfavorable prognosis, close stroke subtype-specific observation by rheumatologists and stroke specialists is recommended after stroke events.

Remote ischemic conditioning for acute ischemic stroke part 2: Study protocol for a randomized controlled trial.

Background: Remote ischemic conditioning (RIC) refers to the application of repeated short periods of ischemia intended to protect remote areas against tissue damage during and after prolonged ischemia. Aim: We aim to evaluate the efficacy of RIC, determined by the modified Rankin Scale (mRS) score at 90 days after stroke onset. Design and methods: This study is an investigator-initiated, multicenter, prospective, randomized, open-label, parallel-group clinical trial. The sample size is 400, comprising 200 patients who will receive RIC and 200 controls. The patients will be divided into three groups according to their National Institutes of Health Stroke Scale score at enrollment: 5-9, mild; 10-14, moderate; 15-20, severe. The RIC protocol will be comprised of four cycles, each consisting of 5 min of blood pressure cuff inflation (at 200 mmHg or 50 mmHg above the systolic blood pressure) followed by 5 min of reperfusion, with the cuff placed on the thigh on the unaffected side. The control group will only undergo blood pressure measurements before and after the intervention period. This trial is registered with the UMIN Clinical Trial Registry (https://www.umin.ac.jp/: UMIN000046225). Study outcome: The primary outcome will be a good functional outcome as determined by the mRS score at 90 days after stroke onset, with a target mRS score of 0-1 in the mild group, 0-2 in the moderate group, and 0-3 in the severe group. Discussion: This trial may help determine whether RIC should be recommended as a routine clinical strategy for patients with ischemic stroke.

[COVID-19 Vaccine-Induced Thrombosis with Thrombocytopenia Syndrome].

Thrombosis with thrombocytopenia syndrome (TTS) induced by the coronavirus disease 2019 vaccine is characterized by thrombocytopenia and thrombosis. Positivity for the anti-platelet factor 4-antibody is related to TTS pathophysiology, similar to heparin-induced thrombocytopenia. Although TTS is very rare, with an incidence of almost 1/100,000 cases, physicians need to keep in mind this adverse reaction that can lead to serious symptoms and death. Prompt treatment should be initiated in cases of suspected TTS.

Short-term or long-term outcomes for stroke patients with cancer according to biological markers.

BACKGROUND: Although hypercoagulability using D-dimer levels may be a useful marker for predicting outcomes in ischemic stroke patients with cancer, other biological markers for predicting outcomes are unclear. We aimed to investigate the associations between several biological markers and short-term or long-term outcomes among ischemic stroke patients with cancer. METHODS: Consecutive acute ischemic stroke patients with cancer (n = 309) were registered. Biological markers such as hemoglobin, albumin, C-reactive protein and D-dimer levels were assessed. Stroke outcomes, namely, a 3-month modified Rankin Scale score indicating poor functional outcome (mRS score of 3-6) and 1-year survival, were assessed. RESULTS: Of the 277 patients who could be assessed for 3 months outcome, 131 patients (47.3%) had a poor outcome at 3 months. Multivariable analysis revealed that increased D-dimer levels and decreased albumin levels were independently associated with poor stroke outcomes (adjusted odds ratio [aOR]: 1.04, 95% confidence interval [CI]: 1.00-1.08, and aOR: 0.50, 95% CI: 0.31-0.80, respectively). Of 309 patients, 70 patients (22.7%) died during the follow-up period (median, 241 days). Multivariate Cox proportional hazard analyses showed that high D-dimer levels and hypoalbuminemia were independently associated with mortality (adjusted hazard ratio [aHR]: 2.65, 95% CI: 1.37-5.12, and aHR: 2.29, 95% CI: 1.21-4.49, respectively). The effect of each biological marker on mortality was notably observed among patients with active cancer but not among those with nonactive cancer. CONCLUSION: Low albumin levels were independently associated with short- and long-term outcomes, as were D-dimer levels, in acute ischemic stroke patients with cancer.

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.

An Older Thrombus Delays Reperfusion after Mechanical Thrombectomy for Ischemic Stroke.

BACKGROUND: Thrombosis is a dynamic process, and a thrombus undergoes physical and biochemical changes that may alter its response to reperfusion therapy. This study assessed whether thrombus age influenced reperfusion quality and outcomes after mechanical thrombectomy for cerebral embolism. METHODS: We retrospectively evaluated 185 stroke patients and thrombi that were collected during mechanical thrombectomy at three stroke centers. Thrombi were pathologically classified as fresh or older based on their granulocytes' nuclear morphology and organization. Thrombus components were quantified, and the extent of NETosis (the process of neutrophil extracellular trap formation) was assessed using the density of citrullinated histone H3-positive cells. Baseline patient characteristics, thrombus features, endovascular procedures, and functional outcomes were compared according to thrombus age. RESULTS: Fresh thrombi were acquired from 43 patients, and older thrombi were acquired from 142 patients. Older thrombi had a lower erythrocyte content (p < 0.001) and higher extent of NETosis (p = 0.006). Restricted mean survival time analysis revealed that older thrombi were associated with longer puncture-to-reperfusion times (difference: 15.6 minutes longer for older thrombi, p = 0.002). This association remained significant even after adjustment for erythrocyte content and the extent of NETosis (adjusted difference: 10.8 minutes, 95% confidence interval [CI]: 0.6-21.1 minutes, p = 0.039). Compared with fresh thrombi, older thrombi required more device passes before reperfusion (p < 0.001) and were associated with poorer functional outcomes (adjusted common odds ratio: 0.49; 95% CI: 0.24-0.99). CONCLUSION: An older thrombus delays reperfusion after mechanical thrombectomy for ischemic stroke. Adding therapies targeting thrombus maturation may improve the efficacy of mechanical thrombectomy.

Clinical characteristics and tumor markers in ischemic stroke patients with active cancer.

Cancer-associated ischemic stroke (CAS) refers to a hypercoagulation disorder related to malignant tumors, especially adenocarcinoma. Carbohydrate antigen (CA) 125 is a mucinous serum marker that might reflect hypercoagulation status, but the association between CA 125 and CAS is unclear across various types of cancer. The aim of this study was to investigate the associations among tumor markers, coagulation markers, and clinical factors in acute ischemic stroke (AIS) patients with active cancer. Consecutive AIS patients with active cancer (a diagnosis or ongoing active therapy for cancer within 6 months) were prospectively enrolled at four hospitals. D-dimer, C-reactive protein (CRP), carcinoembryonic antigen (CEA), CA19-9, and CA 125 levels were measured. Of 120 AIS patients with active cancer, 47 were diagnosed with CAS. CA 125 had the strongest correlations with D-dimer and CRP (ρ = 0.543, p < 0.001 and ρ = 0.452, p < 0.001, respectively). The areas under the receiver-operating characteristic curves for the diagnosis of CAS were 0.812 (95% CI 0.718-0.878) for CA 125, 0.714 (95% CI 0.602-0.801) for CEA, and 0.663 (95% CI 0.552-0.759) for CA 19-9. Multivariable analysis revealed that CA 125 levels in the highest quartile (OR 2.91, 95% CI 1.68-5.53), multiple lesions in multiple vascular territories observed on diffusion-weighted imaging, the absence of dyslipidemia, and the absence of atrial fibrillation were independently associated with CAS. Increased CA 125 levels, which indicate hypercoagulability, were useful for diagnosing CAS in AIS patients with active cancer.