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.

Revascularization to the ACA: effectiveness and variation of the STA-RAG-A3 bonnet bypass.

BACKGROUND: The effectiveness of bypass surgery in patients with atherothrombotic ischemia in the anterior cerebral artery (ACA) domain remains unclear. In this study, three cases with ischemia in the ACA territory underwent revascularization surgery using superficial temporal artery (STA)-radial artery graft (RAG)-A3 (pericallosal artery) bonnet bypass. Herein, we discuss the effectiveness and variations of this approach. METHODS: Among 182 consecutive patients with atherothrombotic ischemic stroke admitted to the NTT Medical Center, Tokyo, from April 2017 to May 2021, three patients with hemodynamic insufficiency in the extensive ACA territory beyond the recent infarct area were treated using STA-RAG-A3 bonnet bypass. RESULTS: One patient with bilateral severe cerebral blood flow (CBF) deficiency required additional A3-A3 and STA-middle cerebral artery single bypass in conjunction with STA-RAG-A3 bypass. There were no complications associated with the surgical procedure. The patients' hemodynamic study results and neurocognitive performances improved dramatically after surgery. CONCLUSION: Our results suggest the efficacy of STA-RAG-A3 bypass for atherothrombotic ACA ischemia. However, because the number of cases was too small to generalize our results, more cases and thorough pre- and postoperative hemodynamic studies are necessary to prove the validity of the approach.

Effect of Mechanical Thrombectomy Without vs With Intravenous Thrombolysis on Functional Outcome Among Patients With Acute Ischemic Stroke: The SKIP Randomized Clinical Trial.

IMPORTANCE: Whether intravenous thrombolysis is needed in combination with mechanical thrombectomy in patients with acute large vessel occlusion stroke is unclear. OBJECTIVE: To examine whether mechanical thrombectomy alone is noninferior to combined intravenous thrombolysis plus mechanical thrombectomy for favorable poststroke outcome. DESIGN, SETTING, AND PARTICIPANTS: Investigator-initiated, multicenter, randomized, open-label, noninferiority clinical trial in 204 patients with acute ischemic stroke due to large vessel occlusion enrolled at 23 hospital networks in Japan from January 1, 2017, to July 31, 2019, with final follow-up on October 31, 2019. INTERVENTIONS: Patients were randomly assigned to mechanical thrombectomy alone (n = 101) or combined intravenous thrombolysis (alteplase at a 0.6-mg/kg dose) plus mechanical thrombectomy (n = 103). MAIN OUTCOMES AND MEASURES: The primary efficacy end point was a favorable outcome defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 2 at 90 days, with a noninferiority margin odds ratio of 0.74, assessed using a 1-sided significance threshold of .025 (97.5% CI). There were 7 prespecified secondary efficacy end points, including mortality by day 90. There were 4 prespecified safety end points, including any intracerebral hemorrhage and symptomatic intracerebral hemorrhage within 36 hours. RESULTS: Among 204 patients (median age, 74 years; 62.7% men; median National Institutes of Health Stroke Scale score, 18), all patients completed the trial. Favorable outcome occurred in 60 patients (59.4%) in the mechanical thrombectomy alone group and 59 patients (57.3%) in the combined intravenous thrombolysis plus mechanical thrombectomy group, with no significant between-group difference (difference, 2.1% [1-sided 97.5% CI, -11.4% to ∞]; odds ratio, 1.09 [1-sided 97.5% CI, 0.63 to ∞]; P = .18 for noninferiority). Among the 7 secondary efficacy end points and 4 safety end points, 10 were not significantly different, including mortality at 90 days (8 [7.9%] vs 9 [8.7%]; difference, -0.8% [95% CI, -9.5% to 7.8%]; odds ratio, 0.90 [95% CI, 0.33 to 2.43]; P > .99). Any intracerebral hemorrhage was observed less frequently in the mechanical thrombectomy alone group than in the combined group (34 [33.7%] vs 52 [50.5%]; difference, -16.8% [95% CI, -32.1% to -1.6%]; odds ratio, 0.50 [95% CI, 0.28 to 0.88]; P = .02). Symptomatic intracerebral hemorrhage was not significantly different between groups (6 [5.9%] vs 8 [7.7%]; difference, -1.8% [95% CI, -9.7% to 6.1%]; odds ratio, 0.75 [95% CI, 0.25 to 2.24]; P = .78). CONCLUSIONS AND RELEVANCE: Among patients with acute large vessel occlusion stroke, mechanical thrombectomy alone, compared with combined intravenous thrombolysis plus mechanical thrombectomy, failed to demonstrate noninferiority regarding favorable functional outcome. However, the wide confidence intervals around the effect estimate also did not allow a conclusion of inferiority. TRIAL REGISTRATION: umin.ac.jp/ctr Identifier: UMIN000021488.

Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Associated With a Novel In-Frame Mutation in the NOTCH3 Gene in a Japanese Patient.

Here, we report a case involving a 67-year-old Japanese woman with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) associated with a novel in-frame complex rearrangement in the NOTCH3 gene. The patient had gradually developed cognitive impairment since the occurrence of an ischemic stroke at the age of 53 years. Her mother had a history of stroke and dementia. Fluid-attenuated inversion recovery magnetic resonance imaging of the brain showed hyperintense lesions in the bilateral temporal poles, external capsules, and periventricular white matter accompanied by multiple cerebral microbleeds on T2*-weighted gradient-echo imaging. A novel in-frame mutation (c.598_610delinsAGAACCC) resulting in the loss of Cys201 in the fifth epidermal growth factor-like repeat of NOTCH3 was identified; this led to a diagnosis of CADASIL. In summary, we report a novel pathogenic mutation (NOTCH3 c.598_610delinsAGAACCC; p.Pro200_Ser204delinsArgThrPro) associated with CADASIL. Further investigations should elucidate the genotype-phenotype correlations in patients with this in-frame complex rearrangement.

Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants: The PASTA Registry - Study Design and Characteristics.

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

Anticoagulants, Reperfusion Therapy, and Outcomes in Ischemic Stroke Patients With Non-Valvular Atrial Fibrillation　- A Single-Center, 6-Year Experience of 546 Consecutive Patients.

BACKGROUND: This study investigated changes in anticoagulant use, treatment, and functional outcomes in acute ischemic stroke (AIS) patients with non-valvular atrial fibrillation (NVAF) over a 6-year period. Methods and Results: Patients with AIS and NVAF admitted to our department from April 2011 to March 2017 were analyzed retrospectively. Patients were divided into 3 groups based on the time of the initial visit (Periods 1-3, corresponding to April 2011-March 2013, April 2013-March 2015, and April 2015-March 2017, respectively). Associations between prescribed medication prior to event and stroke severity, reperfusion therapy, and outcomes were assessed. There was no significant change in the rate of insufficient warfarin and inappropriately lowered doses of direct oral anticoagulant (DOAC) treatment over time. The number of patients receiving prior DOAC treatment increased, but neurological severity on admission was milder than in the other 2 groups. The rate of reperfusion therapy increased from 19.9% (Period 1) to 42.7% (Period 3) for moderate-to-severe stroke patients. Multivariate logistic regression analysis revealed that reperfusion therapy was independently positively associated with good functional outcomes, but negatively associated with mortality (odds ratios [95% confidence intervals] 7.14 [3.34-15.29] and 0.13 [0.008-0.69], respectively). CONCLUSIONS: Inappropriate anticoagulant use for stroke patients with NVAF did not decrease over time. An increase in reperfusion therapy was a strong factor in improved functional outcomes and mortality.

Insufficient Warfarin Therapy Is Associated With Higher Severity of Stroke Than No Anticoagulation in Patients With Atrial Fibrillation and Acute Anterior-Circulation Stroke.

BACKGROUND: Insufficient anticoagulant intensity on admission is common in stroke patients with atrial fibrillation (AF) on vitamin K antagonist (VKA) therapy. Nevertheless, the effects of VKA under-treatment on stroke severity or arterial occlusion are not well known. The aim of the present study was to investigate the relationship between insufficient VKA therapy and stroke severity, or the site of arterial occlusion in patients with acute ischemic stroke (AIS) and AF.Methods and Results:From March 2011 through July 2016, 446 consecutive patients with AF and AIS were recruited. Of the 446 patients, 364 (167 women; median age, 79 years; IQR, 71-86 years) with anterior-circulation stroke were assessed to investigate the effects of insufficient VKA. Of these, 281 were on no anticoagulant, 53 were undertreated with a VKA, and 30 were sufficiently treated with VKA on admission (PT-INR ≥2.0 for patients <70 years and PT-INR ≥1.6 for ≥70 years old). On multivariate analysis, insufficient VKA was independently associated with severe stroke (i.e., initial NIHSS score ≥10; OR, 2.70, P=0.022) and higher prevalence of proximal artery occlusion (OR, 1.91; P=0.039) compared with no anticoagulant therapy. CONCLUSIONS: Insufficient VKA therapy on admission was associated with higher severity of stroke and higher prevalence of proximal artery occlusion in patients with AF and acute anterior-circulation stroke compared with no anticoagulant medication.

In Hyperacute Recanalization Therapy, Early Hospital Arrival Improves Outcome in Patients with Large Artery Occlusion.

BACKGROUND: It is unknown whether the effect of onset---to-door (OTD) time on clinical outcomes differs between -patients with and without large artery occlusion (LAO) who undergo hyperacute recanalization therapy. METHODS: Hyperacute recanalization therapy includes intravenous thrombolysis tissue-plasminogen activator (tPA), and endovascular therapy (EVT). Favorable clinical outcome was defined as modified Rankin Scale of ≤2 at discharge. RESULTS: Among 164 patients, 117 (71%) patients received tPA, 86 (52%) received EVT, and 39 (24%) received tPA and EVT. One hundred and fifteen patients (70%) were classified into the LAO group and 49 (30%) into the non-LAO group. In the total cohort, multivariate regression analysis showed OTD time (OR 0.809 [95% CI 0.693-0.944], p = 0.007) was an independent factor related to the favorable outcome. Similarly, among patients with LAO, OTD was an independent negative factor for the favorable outcome (0.779 [0.646-0.940], p = 0.009). On the contrary, OTD was not associated with the favorable outcome (1.5 [0.7-2.5] vs. 1.7 [1.1-3.2], p = 0.155) in patients without LAO. This was confirmed with multivariate regression analysis, which did not show OTD to be an independent factor for the favorable outcome (0.900 [0.656-1.236], p = 0.516). CONCLUSION: The effect of early hospital arrival on clinical outcome differed between patients with and without LAO.

Thrombus Reformation in the Pulmonary Vein Stump Confirmed 16 Months After Cerebral Embolism on the Day After Left Upper Lobectomy for Lung Cancer.

Cerebral embolism is a very serious complication after lung cancer surgery. In such cases, cerebral embolism is caused by a thrombus formed in the pulmonary vein stump. Most such cases have been reported to occur within 10 days after left upper lobectomy. The patients were treated with anticoagulation therapy to prevent the recurrence of cerebral embolism, and recurrence or thrombus reformation has not been reported to the best of our knowledge. We present a 68-year-old man with a cerebral embolism detected on the day after left upper pulmonary lobectomy for lung cancer. The patient was treated with unfractionated heparin and his neurological symptoms improved. Heparin treatment was subsequently changed to aspirin for the prevention of recurrence; however, thrombus formation in the vein stump was asymptomatically confirmed 16 months after the surgery by contrast-enhanced computed tomography. This is the first case to our knowledge of thrombus reformation in the pulmonary vein stump after a cerebral embolism associated with lung cancer surgery. In our case, anticoagulation therapy was not continued to prevent recurrence, and antiplatelet therapy was performed instead, which might be associated with the thrombus reformation.

Low Free Triiodothyronine at Admission Predicts Poststroke Infection.

BACKGROUND: Poststroke infection (PSI) is common and is usually associated with a severe prognosis. We investigated the association between PSI and thyroid hormones, which are critical to immune regulation, in patients with acute stroke. METHODS: We retrospectively enrolled 520 consecutive patients with acute ischemic stroke (326 men; age, 71.9 ± 13.2 years) admitted to our department between September 2014 and June 2016. The impact of serum thyroid hormone levels measured at admission (thyroid-stimulating hormone [TSH], free triiodothyronine [FT3], and free thyroxine [FT4]) on the PSI was evaluated using multivariate logistic regression analysis. RESULTS: We diagnosed 107 patients (20.6%; pneumonia, 65; urinary tract infection, 19; others, 23) with PSIs. While age (P <.001), body mass index (P = .0012), preadmission modified Rankin scale score (P = .0001), National Institutes of Health Stroke Scale score on admission (P <.001), admission FT3 level (P <.001), atrial fibrillation (P <.001), and ischemic heart disease (P = .0451) were significantly associated with PSI, we found no relationship among TSH levels, FT4 levels, and PSI occurrence. After multivariate adjustment, patients with PSIs were more frequently in the Q1 quartile (≤2.25 pg/mL) than in the Q2 (2.26-2.55 pg/mL; P = .0251), Q3 (2.56-2.89 pg/mL; P = .0007), or Q4 (≥2.90 pg/mL; P = .0010) quartiles of FT3 levels. Moreover, low FT3 levels (<2.29 pg/mL) were independently associated with PSI occurrence (P = .0013). CONCLUSIONS: Low FT3 levels at admission are independently associated with PSI occurrence.

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.

High urinary albumin/creatinine ratio at admission predicts poor functional outcome in patients with acute ischaemic stroke.

AIM: Albuminuria and a low estimated glomerular filtration rate (eGFR) are widely recognized indices of kidney dysfunction and have been linked to cardiovascular events, including stroke. We evaluated albuminuria, measured using the urinary albumin/creatinine ratio (UACR), and the eGFR in the acute phase of ischaemic stroke, and investigated the clinical characteristics of ischaemic stroke patients with and those without kidney dysfunction. METHODS: The study included 422 consecutive patients admitted between June 2010 and May 2012. General blood and urine examinations were performed at admission. Kidney dysfunction was defined as a low eGFR (<60 mL/min per 1.73 m2 ), high albuminuria (≥30 mg/g creatinine), or both. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) at admission and the modified Rankin scale (mRS) at discharge. A poor outcome was defined as a mRS score of 3-5 or death. The impacts of the eGFR and UACR on outcomes at discharge were evaluated using multiple logistic regression analysis. RESULTS: Kidney dysfunction was diagnosed in 278 of the 422 patients (65.9%). The eGFR was significantly lower and UACR was significantly higher in patients with a poor outcome than in those with a good outcome. In multivariate analyses performed after adjusting for confounding factors, UACR >31.2 mg/g creatinine (OR, 2.58; 95% CI, 1.52-4.43; P = 0.0005) was independently associated with a poor outcome, while a low eGFR was not associated. CONCLUSIONS: A high UACR at admission may predict a poor outcome at discharge in patients with acute ischaemic stroke.

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.

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.

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.

Safety of Antithrombotic Therapy within 24 Hours after Recombinant Tissue-Plasminogen Activator Treatment for Large-Artery Atherosclerosis Stroke: Insights from Emergent PTA/CAS Cases.

BACKGROUND: Antithrombotic therapy (AT) should generally be avoided within 24 hours after recombinant tissue-plasminogen activator (rt-PA) treatment but should be considered in patients with large-artery atherosclerosis (LAA) who undergo concomitant emergent endovascular treatment (EVT). The aim of the present study was to assess the safety of AT within 24 hours after rt-PA treatment in patients with hyperacute ischemic stroke due to LAA who received concomitant EVT. METHODS: From January 2013 through July 2019, consecutive patients with acute ischemic cerebrovascular disease due to LAA who were admitted within 6 hours from symptom onset were recruited. The patients were classified into six groups based on the reperfusion treatment and early (within 24 hours) AT from rt-PA treatment. Safety outcomes were compared among the groups. RESULTS: A total of 155 patients (35 women [23%], median age 74 [IQR 66-79] years; NIHSS score 3 [1-10]) were included in the present study. Of these, 73 (47%) received no reperfusion therapy, 24 (15%) received rt-PA treatment and early AT, seven (6%) received rt-PA without early AT, 26 (17%) received EVT only, six (4%) received both rt-PA and EVT without early AT, and 19 (12%) received rt-PA and EVT with early AT. AT was administered a median of 3.9 (1.6-8.0) hours after rt-PA in patients with rt-PA+EVT with early AT. AT within 24 hours after rt-PA and EVT treatment did not increase hemorrhagic complications (p > 0.05 for all). CONCLUSION: In this retrospective analyses, early AT administration for patients with hyperacute stroke due to LAA treated with rt-PA plus EVT did not increase hemorrhagic events.

The randomized study of enteral nutrition with rapid versus conventional administration in acute stroke patients; the protocol of rapid EN trial.

Rationale: Enteral nutrition is beneficial for stroke patients with oral intake difficulties. However, it is time consuming and may interfere with routine medical care. Therefore, there is a clinical benefit if enteral nutrition can be safely administered in a short time. Although our retrospective study showed the safety of rapid administration, it remains unclear whether rapid administration of enteral nutrition is as safe as conventional administration. Aim: The randomized study of Enteral Nutrition with Rapid versus conventional administration in acute stroke patients (Rapid EN trial) aims to clarify the safety of rapid feeding of enteral nutrition compared with conventional feeding. Methods and design: This is an investigator-initiated, multicenter, prospective, randomized, open-label, blinded end-point clinical trial. Eligible criteria include acute stroke patients who have difficulty with oral intake defined as severe altered consciousness (Japan Coma Scale 10-300) or modified water swallowing test <4. The target enrollment is 700 patients, with 350 patients receiving rapid enteral nutrition at a rate of 100 mL in 5 min (Rapid EN group) and 350 patients receiving conventional enteral nutrition at a rate of 100 mL in 30 min (Conventional EN group). Study outcome: The primary outcome is the incidence of one or more complications of vomiting or diarrhea or pneumonia within 7 days would be non-inferior in the rapid EN group compared to the conventional EN group. Secondary outcomes were total time spent on enteral nutrition within 7 days from enteral nutrition, the incidence of vomiting, diarrhea and pneumonia within 3 or 7 days, and the rate of favorable clinical outcome. Discussion: Since no previous reports have focused on the speed of administration, we felt it was necessary to prove the safety of rapid administration. If this study shows positive results, it will not only benefit patients, but also reduce the burden of medical care. We believe this study is novel and will be useful in clinical practice. Clinical trial registration: https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000046610 Identifier UMIN000046610.

Low serum n-3 polyunsaturated fatty acid/n-6 polyunsaturated fatty acid ratio predicts neurological deterioration in Japanese patients with acute ischemic stroke.

BACKGROUND: Epidemiological and clinical trials have shown that n-3 polyunsaturated fatty acids (PUFAs) reduce the incidence of coronary heart disease or stroke. However, the association between PUFAs and acute-phase stroke has not yet been thoroughly studied. We investigated the impact of serum PUFAs on early neurological deterioration (END) in patients with acute ischemic stroke. METHODS: In this retrospective study, we enrolled 281 Japanese patients (mean age: 75 ± 13 years; 165 males) with acute ischemic stroke diagnosed within 24 h of onset. General blood examinations, including PUFAs (n-3 PUFAs: eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA, and n-6 PUFAs: arachidonic acid, AA), were performed on admission. Other risk factors and comorbidities were also examined. END was defined as a ≥2-point increase in the National Institutes of Health Stroke Scale (NIHSS) score within a 72-hour period. Statistical significance between the END and non-END group was assessed using Wilcoxon rank sum tests or Student's t tests for categorical variables. Multiple logistic regression analyses were performed to identify predictors of END. RESULTS: END was observed in 75 patients (26.7%). Diabetes mellitus (p = 0.003), high-sensitivity C-reactive protein (hs-CRP) level (p < 0.001), prior stroke (p = 0.035), ischemic heart disease (p = 0.029), EPA/AA ratio (p = 0.003), DHA/AA ratio (p = 0.002), EPA+DHA/AA ratio (p = 0.002), diagnosis of small vessel disease (p = 0.004) and admission NIHSS score (p < 0.001) were significantly associated with END. We used separate multiple logistic regression analyses for the EPA/AA, DHA/AA and EPA+DHA/AA ratios, because EPA and DHA are considered covariant factors (r = 0.544; p < 0.0001). Multiple logistic regression analyses showed that END was positively associated with diabetes mellitus, hs-CRP level and NIHSS score on admission, and negatively associated with the EPA/AA ratio (odds ratio, OR: 0.18; 95% confidence interval, CI: 0.05-0.58; p = 0.003), DHA/AA ratio (OR: 0.045; 95% CI: 0.006-0.30; p = 0.001), EPA+DHA/AA ratio (OR: 0.45; 95% CI: 0.26-0.74; p = 0.002) and diagnosis of small vessel disease. CONCLUSIONS: Our data suggest that a low serum n-3 PUFA/n-6 PUFA ratio on admission may predict neurological deterioration in Japanese patients with acute ischemic stroke. Large-scale prospective studies are further required to clarify the role of PUFAs in the acute phase of ischemic stroke.

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.