Two-Year Outcomes of Anticoagulation for Acute Ischemic Stroke With Nonvalvular Atrial Fibrillation　- SAMURAI-NVAF Study.

BACKGROUND: We determined the 2-year long-term risk-benefit profile in patients with stroke or transient ischemic attack (TIA) receiving warfarin or direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry in Japan.Methods and Results:NVAF patients within 7 days after onset of ischemic stroke/TIA were enrolled in 18 stroke centers. Outcome measures included ischemic and bleeding events and death in the 2-year follow-up period. We enrolled 1,116 patients taking either warfarin (650 patients) or DOACs (466 patients) at acute hospital discharge. DOAC users were younger and had lower National Institutes of Health Stroke Scale, CHADS2and discharge modified Rankin Scale scores than warfarin users (P<0.0001 each). Incidences of stroke/systemic embolism (adjusted hazard ratio, 1.07; 95% CI, 0.66-1.72), all ischemic events (1.13; 0.72-1.75), and ischemic stroke/TIA (1.58; 0.95-2.62) were similar between groups. Risks of intracranial hemorrhage (0.32; 0.09-0.97) and death (0.41; 0.26-0.63) were significantly lower for DOAC users. Infection was the leading cause of death, accounting for 40% of deaths among warfarin users. CONCLUSIONS: Stroke/TIA patients receiving DOACs for secondary prevention were younger and had lower stroke severity and risk indices than those receiving warfarin. Estimated cumulative incidences of stroke and systemic embolism within 2 years were similar between warfarin and DOACs users, but those of death and intracranial hemorrhage were significantly lower among DOAC users.

Development of Interstitial Lung Disease after Initiation of Apixaban Anticoagulation Therapy.

BACKGROUND: Nonvitamin K antagonist oral anticoagulants may cause interstitial lung disease (ILD) similar to that seen for other cardiovascular drugs. The aim of this study was to determine trends and medical conditions associated with ILD in patients taking apixaban. METHODS: A single-center observational survey conducted between February 2013 and May 2015 examined patients who developed ILD after initiation of apixaban administration. RESULTS: Chest computed tomography showed that 4 (~.45%) out of approximately 870 apixaban users developed ILD. All patients were elderly Japanese men with decreased creatinine clearance who had nonvalvular atrial fibrillation. Three of the four were confirmed smokers, whereas three had a history of lung disease. Dyspnea occurred during the initial week after starting apixaban administration in 3 patients and at 90 days in 1 patient. All patients underwent methylprednisolone pulse therapy, with three requiring mechanical ventilation. Although 2 patients recovered, the other two died of respiratory failure. CONCLUSIONS: Development of ILD during anticoagulation with apixaban is not rare. When apixaban is administered in elderly high-risk patients, subjects need to be carefully monitored for respiratory symptoms. As drug-induced ILD is often reported in Japan, further studies that clarify if these types of cases are common in countries other than Japan will also need to be undertaken.

The Fornix May Play a Key Role in Korsakoff's Amnesia Secondary to Subcallosal Artery Infarction.

BACKGROUND: Subcallosal artery infarction injures the fornix and anterior corpus callosum and sometimes causes Korsakoff's amnesia. We hypothesized that Korsakoff's amnesia might be caused by fornix dysfunction rather than anterior corpus callosum dysfunction in subcallosal artery infarction. METHODS: A systematic review approach was applied to search PubMed and Google Scholar for articles to compare patients who had both bilateral fornix and corpus callosum infarction due to subcallosal artery territory ischemia (vascular event group; V group) with patients who had undergone anterior corpus callosotomy (callosotomy group; C group). RESULTS: The V group comprised 10 patients (mean age, 63 years; median, 69 years; standard deviation (SD), 14.5 years; 5 males, 5 females). The C group comprised 6 patients (mean age, 23.7 years; median, 20 years; SD, 7.3 years; 3 males, 3 females). Six of 10 patients (60%) with subcallosal artery infarction exhibited Korsakoff's amnesia. One patient showed neither confabulation nor amnesia. Conversely, no amnesia episodes were seen in any patients from the C group (p = 0.034). CONCLUSION: Fornix injury, rather than anterior corpus callosum injury, might be the major cause of Korsakoff's amnesia in patients with subcallosal artery infarction.

Feasibility of Mechanical Thrombectomy for Acute Ischemic Stroke Patients Aged 90 Years or Older Compared to Younger Patients.

Mechanical thrombectomy (MT) is a proven treatment for acute ischemic stroke (AIS). However, the efficacy of this treatment is uncertain for very elderly patients. This study aimed to investigate the safety and effectiveness of MT in 90 years or older patients compared with younger patients. We retrospectively reviewed AIS patients treated with MT between October 2018 and June 2020 in our institution. Patients were divided into two groups: aged ≥90 and <90 years. We compared the following factors: functional outcome at discharge, in-hospital death, successful recanalization, and complications. Multivariate logistic regression analysis for the good functional outcome was performed. In consideration of pre-stroke basic activities of very elderly patients, we defined the good functional outcome as modified Rankin Scale (mRS) 0-3. In all, 66 patients were included, and 19 patients (28%) were ≥90 years old. Pre-stoke mRS was higher in ≥90-year-old patients (p = 0.01). In ≥90-year-old patients, we achieved successful recanalization in 17 patients (90%), and only one patient experienced hemorrhagic complication related with the procedure. The good functional outcome (mRS: 0-3) at discharge were six patients (32%) in ≥90 years old versus 19 patients (40%) in <90 years old (p = 0.6). Three patients died in hospital in each group (16% versus 6%) (p = 0.3). Only the stroke severity was negatively related with the good functional outcome in a multivariate analysis. In conclusion, for ≥90-year-old patients compared with younger patients, MT is an equally feasible therapy. Patients should not be excluded from MT based on age alone.

A Young Patient with Emery-Dreifuss Muscular Dystrophy Treated with Endovascular Therapy for Cardioembolic Stroke: A Case Report.

We had a case of Emery-Dreifuss muscular dystrophy (EDMD) in an 18-year-old woman who underwent endovascular therapy for a cardioembolic stroke. At 5 years old, she showed a high creatine kinase level and atrial fibrillation on electrocardiography in our hospital. Finally, she was diagnosed as having EDMD by genetic screening that revealed mutations in the LMNA gene (c.810+1G>T). Before this event, she received no medications. At 18 years old, she was admitted to our hospital>8 hours after the onset of sudden consciousness disturbance. Neurological examination on admission revealed consciousness disturbance and right hemiplegia. Magnetic resonance imaging revealed a cerebral infarction in the left insular cortex and putamen with left internal carotid artery occlusion. We performed endovascular therapy and completely recanalized her left internal carotid artery. Thereafter, her neurological symptoms improved. She was subsequently transferred to a rehabilitation hospital. EDMD is a rare genetic muscular disease that mainly presents with contractures, weakness, and cardiac conduction abnormalities. Although patients with EDMD are young with low CHADS2 score, they have a disease-specific cardiovascular pathogenesis caused by a fatal risk factor. Therefore, we consider anticoagulant therapy necessary to prevent thrombotic events, even if the CHADS2 score is low, in patients with EDMD.

Three-month risk-benefit profile of anticoagulation after stroke with atrial fibrillation: The SAMURAI-Nonvalvular Atrial Fibrillation (NVAF) study.

AIMS: This study was performed to determine the short-term risk-benefit profiles of patients treated with oral anticoagulation for acute ischemic stroke or transient ischemic attack using a multicenter, prospective registry. METHODS: A total of 1137 patients (645 men, 77 ± 10 years old) with acute ischemic stroke/transient ischemic attack taking warfarin (662 patients) or non-vitamin K antagonist oral anticoagulants (dabigatran in 205, rivaroxaban in 245, apixaban in 25 patients) for nonvalvular atrial fibrillation who completed a three-month follow-up survey were studied. Choice of anticoagulants was not randomized. Primary outcome measures were stroke/systemic embolism and major bleeding. RESULTS: Both warfarin and non-vitamin K antagonist oral anticoagulants were initiated within four days after stroke/transient ischemic attack onset in the majority of cases. Non-vitamin K antagonist oral anticoagulant users had lower ischemia- and bleeding-risk indices (CHADS2, CHA2DS2-VASc, HAS-BLED) and milder strokes than warfarin users. The three-month cumulative rate of stroke/systemic embolism was 3.06% (95% CI 1.96%-4.74%) in warfarin users and 2.84% (1.65%-4.83%) in non-vitamin K antagonist oral anticoagulant users (adjusted HR 0.96, 95% CI 0.44-2.04). The rate of major bleeding was 2.61% (1.60%-4.22%) and 1.11% (0.14%-1.08%), respectively (HR 0.63, 0.19-1.78); that for intracranial hemorrhage was marginally significantly lower in non-vitamin K antagonist oral anticoagulant users (HR 0.17, 0.01-1.15). Major bleeding did not occur in non-vitamin K antagonist oral anticoagulant users with a CHADS2 score <4 or those with a discharge modified Rankin Scale score ≤2. CONCLUSIONS: Stroke or systemic embolism during the initial three-month anticoagulation period after stroke/transient ischemic attack was not frequent as compared to previous findings regardless of warfarin or non-vitamin K antagonist oral anticoagulants were used. Intracranial hemorrhage was relatively uncommon in non-vitamin K antagonist oral anticoagulant users, although treatment assignment was not randomized. Early initiation of non-vitamin K antagonist oral anticoagulants during the acute stage of stroke/transient ischemic attack in real-world clinical settings seems safe in bleeding-susceptible Japanese population.

Blood glucose levels during the initial 72 h and 3-month functional outcomes in acute intracerebral hemorrhage: the SAMURAI-ICH study.

PURPOSE: Prognostic values of blood glucose levels following admission remain unclear. We investigated associations between blood glucose levels during the initial 72 h and outcomes of acute ICH. METHODS: Participants comprised hyperacute ICH patients who received intravenous antihypertensive treatment. Blood glucose levels were measured on admission and at 24 and 72 h after starting treatment, along with hemoglobin (Hb)A1c level on admission. Associations with clinical outcomes of hematoma expansion (>33% increase), none to minimal disability (3-month modified Rankin Scale [mRS] 0-1) and bedridden or death (3-month mRS 5-6) were analyzed. RESULTS: Of the 176 patients (70 women; 65 ± 12 years), 30 (18%) showed hematoma expansion, and 33 (19%) had none to minimal disability and 15 (10%) were bedridden or died. On multivariate regression analysis, blood glucose at 24h (per 10mg/dl odds ratio [OR], 0.84; 95% confidence interval [CI], 0.69-0.98) and blood glucose at 72 h (OR, 0.75; 95%CI, 0.59-0.92) were inversely associated with none to minimal disability, and blood glucose at 24h (OR, 1.14; 95%CI, 1.00-1.30) was positively associated with bedridden or death. No parameters were associated with hematoma expansion. CONCLUSIONS: High blood glucose levels at 24 and 72 h were independently associated with poor functional outcomes 3 months after ICH. We need to investigate whether blood glucose control during the acute period ameliorates clinical outcomes.

THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6 mg/kg (THAWS) Trial.

RATIONALE: Because of lack of information regarding timing of stroke, patients who suffer stroke during sleep are generally ineligible for intravenous thrombolysis, although many of these patients could potentially recover with this treatment. Magnetic resonance image findings with positive diffusion-weighted imaging and no marked parenchymal hyperintensity on fluid-attenuated inversion recovery (negative pattern) can identify acute ischemic stroke patients within 4·5 h from symptom onset. AIMS: The THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6 mg/kg trial aims to determine the efficacy and safety of intravenous thrombolysis with alteplase at 0·6 mg/kg body weight, the approved dose for Japanese stroke patients, using magnetic resonance image-based selection in ischemic stroke patients with unclear time of symptom onset, and compare findings with standard treatment. DESIGN: This is an investigator-initiated, multicenter, prospective, randomized, open-treatment, blinded-end-point clinical trial. The design is similar to the Efficacy and Safety of MRI-based Thrombolysis in Wake-up Stroke trial. Patients with unclear-onset time of stroke symptoms beyond 4·5 h and within 12 h after the time of the last-known-well period and within 4·5 h after symptom recognition, who showed a negative fluid-attenuated inversion recovery pattern, are randomized to either intravenous thrombolysis or standard treatment. STUDY OUTCOMES: The primary efficacy end-point is modified Rankin Scale 0-1 at 90 days. The safety outcome measures are symptomatic intracranial hemorrhage at 22-36 h, and major bleeding and mortality at 90 days. DISCUSSION: This trial may help determine if low-dose alteplase at 0·6 mg/kg should be recommended as a routine clinical strategy for ischemic stroke patients with unclear-onset time.