Anti-Xa Activity and Event Risk in Patients With Direct Factor Xa Inhibitors Initiated Early After Stroke.

BACKGROUND: Measuring anti-Xa activity (AXA) has been reported as useful for predicting future risk of hemorrhagic and ischemic events in stroke patients taking direct factor Xa inhibitors. We evaluated AXA levels of rivaroxaban or apixaban in acute stroke patients with non-valvular atrial fibrillation. Methods and Results: This was a single-center, prospective, observational study. Consecutive patients with acute ischemic stroke or transient ischemic attack who were admitted within 7 days of onset and started taking rivaroxaban or apixaban for NVAF between January 2012 and April 2017 were enrolled. AXA was measured at 2 time points: just before (AXAtrough) and 4 h after (AXApeak) taking rivaroxaban or apixaban on the 2nd day or later of administration. Of 156 patients taking rivaroxaban, hemorrhagic events occurred in 13. Patients with hemorrhagic events had higher AXApeak than those without [median (interquartile range): 1.93 (1.11-3.75) vs. 1.35 (0.80-2.00) IU/mL; P<0.01]. Multivariable-adjusted Cox models showed that AXApeak was independently related to the incidence of hemorrhagic events. Of 169 patients taking apixaban, hemorrhagic events occurred in 11. Patients with hemorrhagic events had higher AXAtrough [2.78 (1.90-3.53) vs. 1.42 (0.93-2.08) IU/mL, P<0.01] and AXApeak [4.05 (3.44-4.72) vs. 2.43 (1.79-3.35) IU/mL, P<0.01] than those without. Both AXAtrough and AXApeak were independently related to the incidence of hemorrhagic events. CONCLUSIONS: In these patients who started rivaroxaban or apixaban early after stroke, AXA levels in the early period were related to future hemorrhagic events.

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 future perspective of acute thrombolytic therapy for acute ischemic stroke].

Intravenous (IV) thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) is the evidence-based treatment for acute ischemic stroke patients, and its position as the standard therapy remains unchanged even though newer clinical evidences of the endovascular therapies emerged. In Japan, IV rt-PA was approved in 2005. One of the problems is the limited therapeutic time range, but it was extended from 3 hours to 4.5 hours after stroke onset in 2012 based on the pooled-data analysis of the major clinical trials. There are also candidates for IV rt-PA therapy among the wake-up and unclear-onset stroke patients. The next challenge is to identify the appropriate thrombolytic targets using the penumbral imaging techniques. The optimal strategies might be established by the ongoing clinical trials in the future.

Predictions of charged charmoniumlike structures with hidden-charm and open-strange channels.

We propose the initial single chiral particle emission mechanism, with which the hidden-charm dikaon decays of higher charmonia and charmoniumlike states are studied. Calculating the distributions of differential decay width, we obtain the line shape of the J/ψK(+) invariant mass spectrum of ψ(i)→J/ψK(+)K(-), where ψ(i)=ψ(4415), Y(4660), and ψ(4790). Our numerical results show that there exist enhancement structures with both hidden-charm and open-strange channels, which are near the D̄(s)(*)/D(*)D̄(s) and D(*)D̄(s)(*)/D̄(*)D(s)(*) thresholds. These charged charmoniumlike structures predicted in this Letter can be accessible in future experiments, especially BESIII, BelleII, and SuperB.

Interictal epileptiform discharges as a predictive biomarker for recurrence of poststroke epilepsy.

Poststroke epilepsy is a major ischaemic/haemorrhagic stroke complication. Seizure recurrence risk estimation and early therapeutic intervention are critical, given the association of poststroke epilepsy with worse functional outcomes, quality of life and greater mortality. Several studies have reported risk factors for seizure recurrence; however, in poststroke epilepsy, the role of EEG in predicting the risk of seizures remains unclear. This multicentre observational study aimed to clarify whether EEG findings constitute a risk factor for seizure recurrence in patients with poststroke epilepsy. Patients with poststroke epilepsy were recruited from the PROgnosis of POst-Stroke Epilepsy study, an observational multicentre cohort study. The enrolled patients with poststroke epilepsy were those admitted at selected hospitals between November 2014 and June 2017. All patients underwent EEG during the interictal period during admission to each hospital and were monitored for seizure recurrence over 1 year. Board-certified neurologists or epileptologists evaluated all EEG findings. We investigated the relationship between EEG findings and seizure recurrence. Among 187 patients with poststroke epilepsy (65 were women with a median age of 75 years) admitted to the lead hospital, 48 (25.7%) had interictal epileptiform discharges on EEG. During the follow-up period (median, 397 days; interquartile range, 337-450 days), interictal epileptiform discharges were positively correlated with seizure recurrence (hazard ratio, 3.82; 95% confidence interval, 2.09-6.97; P < 0.01). The correlation remained significant even after adjusting for age, sex, severity of stroke, type of stroke and generation of antiseizure medications. We detected periodic discharges in 39 patients (20.9%), and spiky/sharp periodic discharges were marginally associated with seizure recurrence (hazard ratio, 1.85; 95% confidence interval, 0.93-3.69; P = 0.08). Analysis of a validation cohort comprising 187 patients with poststroke epilepsy from seven other hospitals corroborated the association between interictal epileptiform discharges and seizure recurrence. We verified that interictal epileptiform discharges are a risk factor for seizure recurrence in patients with poststroke epilepsy. Routine EEG may facilitate the estimation of seizure recurrence risk and the development of therapeutic regimens for poststroke epilepsy.

Impact of Seizure Recurrence on 1-Year Functional Outcome and Mortality in Patients With Poststroke Epilepsy.

BACKGROUND AND OBJECTIVES: The functional outcome and mortality of patients with poststroke epilepsy (PSE) have not been assessed in a prospective study. Previous reports have suggested that patients with PSE may suffer from prolonged functional deterioration after a seizure. In this study, we prospectively investigated the functional outcome and mortality of patients with PSE and analyzed the effect of seizure recurrence on the outcomes. METHODS: This is part of the Prognosis of Post-Stroke Epilepsy study, a multicenter, prospective observational cohort study, where 392 patients with PSE (at least 1 unprovoked seizure more than 7 days after the onset of the last symptomatic stroke) were followed for at least 1 year at 8 hospitals in Japan. This study included only PSE patients with a first-ever seizure and assessed their functional decline and mortality at 1 year. Functional decline was defined as an increase in modified Rankin Scale (mRS) score at 1 year compared with baseline, excluding death. The associations between the seizure recurrence and the outcomes were analyzed statistically. RESULTS: A total of 211 patients (median age of 75 years; median mRS score of 3) were identified. At 1 year, 50 patients (23.7%) experienced seizure recurrence. Regarding outcomes, 25 patients (11.8%) demonstrated functional decline and 20 (9.5%) had died. Most patients died of pneumonia or cardiac disease (7 patients each), and no known causes of death were directly related to recurrent seizures. Seizure recurrence was significantly associated with functional decline (odds ratio [OR] 2.96, 95% CI 1.25-7.03, p = 0.01), even after adjusting for potential confounders (adjusted OR 3.26, 95% CI 1.27-8.36, p = 0.01), but not with mortality (OR 0.79, 95% CI 0.25-2.48, p = 0.68). Moreover, there was a significant trend where patients with more recurrent seizures were more likely to have functional decline (8.7%, 20.6%, and 28.6% in none, 1, and 2 or more recurrent seizures, respectively; p = 0.006). DISCUSSION: One-year functional outcome and mortality of patients with PSE were poor. Seizure recurrence was significantly associated with functional outcome, but not with mortality. Further studies are needed to ascertain whether early and adequate antiseizure treatment can prevent the functional deterioration of patients with PSE.

Prestroke glycemic control is associated with the functional outcome in acute ischemic stroke: the Fukuoka Stroke Registry.

BACKGROUND AND PURPOSE: Diabetes mellitus is an established risk factor for stroke. However, it is uncertain whether prestroke glycemic control (PSGC) status affects clinical outcomes of acute ischemic stroke. The aim of this study was to elucidate the association between PSGC status and neurological or functional outcomes in patients with acute ischemic stroke. METHODS: From the Fukuoka Stroke Registry (FSR), a multicenter stroke registry in Japan, 3627 patients with first-ever ischemic stroke within 24 hours after onset were included in the present analysis. The patients were categorized into 4 groups based on their PSGC status: excellent (hemoglobin [Hb] A1c on admission<6.2%), good (6.2-6.8%), fair (6.9-8.3%) and poor (≥8.4%). Study outcomes were neurological improvement (≥4 points decrease in the National Institutes of Health Stroke Scale [NIHSS] score during hospitalization or 0 points on NIHSS score at discharge), neurological deterioration (≥1 point increase in NIHSS score) and poor functional outcome (death or dependency at discharge, modified Rankin Scale 2-6). RESULTS: The age- and sex-adjusted ORs for neurological improvement were lower, and those for neurological deterioration and a poor functional outcome were higher in patients with poorer PSGC status. After adjusting for multiple confounding factors, these trends were unchanged (all probability values for trends were <0.002). These findings were comparable in patients with noncardioembolic and cardioembolic infarctions. CONCLUSIONS: In ischemic stroke patients, HbA1c on admission was an independent significant predictor for neurological and functional outcomes.

Validation of automated quantitation of myocardial perfusion and fatty acid metabolism abnormalities on SPECT images.

BACKGROUND: Myocardial perfusion and fatty acid imaging have played important roles in the risk stratification of patients with coronary artery disease (CAD). However, visual image assessment requires considerable experience and training. Therefore, an automated program has been developed that can quantify perfusion and fatty acid uptake on myocardial single emission computed tomography (SPECT). The present study aimed to validate the automated quantitative program. METHODS AND RESULTS: A total of 50 patients were studied with known or suspected CAD who underwent stress ²°¹Thallium (²°¹Tl) and resting ¹²³I-labelled ß-methyl iodophenyl pentadecanoic acid (BMIPP) SPECT. The SPECT images were quantified in 17 segments visually and using our Heart Score View software. Values were compared with those in a normal Japanese database and calculated summed stress (SSS), summed rest (SRS), summed difference (SDS), and summed BMIPP scores for each modality. Summed scores obtained using standard visual analysis and Heart Score View significantly correlated (²°¹Tl: SSS: r=0.934; SRS: r=0.827; SDS: r=0.743 summed BMIPP score: r=0.913) (each P<0.001) and Bland-Altman analysis revealed good agreement between the 2 approaches. CONCLUSIONS: Correlations between scores determined using Heart Score View software and standard visual interpretation were linear for both perfusion and fatty acid images. Thus, our new automated program might be useful for the risk stratification of patients with CAD in the clinical setting.

Antiseizure medications for post-stroke epilepsy: A real-world prospective cohort study.

BACKGROUND AND PURPOSE: The management of post-stroke epilepsy (PSE) should ideally include prevention of both seizure and adverse effects; however, an optimal antiseizure medications (ASM) regimen has yet been established. The purpose of this study is to assess seizure recurrence, retention, and tolerability of older-generation and newer-generation ASM for PSE. METHODS: This prospective multicenter cohort study (PROgnosis of Post-Stroke Epilepsy [PROPOSE] study) was conducted from November 2014 to September 2019 at eight hospitals. A total of 372 patients admitted and treated with ASM at discharge were recruited. Due to the non-interventional nature of the study, ASM regimen was not adjusted and followed standard hospital practices. The primary outcome was seizure recurrence in patients receiving older-generation and newer-generation ASM. The secondary outcomes were the retention and tolerability of ASM regimens. RESULTS: Of the 372 PSE patients with ASM at discharge (median [IQR] age, 73 [64-81] years; 139 women [37.4%]), 36 were treated with older-generation, 286 with newer-generation, and 50 with mixed-generation ASM. In older- and newer-generation ASM groups (n = 322), 98 patients (30.4%) had recurrent seizures and 91 patients (28.3%) switched ASM regimen during the follow-up (371 [347-420] days). Seizure recurrence was lower in newer-generation, compared with the older-generation, ASM (hazard ratio [HR], 0.42, 95%CI 0.27-0.70; p = .0013). ASM regimen withdrawal and change of dosages were lower in newer-generation ASM (HR, 0.34, 95% CI 0.21-0.56, p < .0001). CONCLUSIONS: Newer-generation ASM possess advantages over older-generation ASM for secondary prophylaxis of post-stroke seizures in clinical practice.

[A case of pneumococcal meningitis with reversible arterial stenosis].

A 72-year-old male was diagnosed pneumococcal meningitis and we started treatment with antibacterial drugs and corticosteroids. On the 6th day, his consciousness level decreased. On the 7th day DWI of MRI showed a new infarction in bilateral cerebellar, and MRA showed multiple arterial stenosis. On the 12th day, CT angiography showed expansion of cerebral infarction and progress of diffuse stenosis. After that the stenosis improved over time, it disappeared on the 39th day. These results suggest that vasospasm is involved in the pathology of vascular stenosis.

Concentrations of dabigatran administered after acute ischemic stroke.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate the anticoagulation intensity of dabigatran for acute ischemic stroke patients and hemorrhagic/ischemic events after early initiation of dabigatran. METHODS: Acute ischemic stroke/transient ischemic attack (TIA) patients admitted to our hospital who started dabigatran from January 2012 to December 2017 were studied. Blood samples were drawn just before (0 h) and 4 h after dabigatran at a median of 5 days after starting dabigatran to measure dabigatran concentrations (C0h, C4h) based on the thrombin clotting time assay (Hemoclot®). RESULTS: Of the 70 patients (54 men, 69 ± 9 y), 14 started dabigatran after a TIA, and 56 started it after an ischemic stroke a median of 5 days after onset. C0h, C4h was 82.5 ± 58.0, 143.1 ± 98.2 ng/dl (150 mg BID, 35 patients) and 50.6 ± 40.9, 91.2 ± 64.7 ng/ml (110 mg BID, 35 patients). During a median follow-up of 382 (IQR 109-688) days of all 70 patients, five had clinical events. Three patients had bleeding events, two with nasal bleeding (C0h, C4h: 50, 80 ng/ml, C0h, C4h: 91, 173 ng/ml) and one with GI bleeding (C0h, C4h: 5, 5 ng/ml). Two patients had ischemic events, one with ischemic stroke (C0h, C4h: 10, 50 ng/ml) and another with acute myocardial infarction (C0h, C4h: 40, 40 ng/ml). CONCLUSIONS: There was no obvious relationship between dabigatran concentration and hemorrhagic/ischemic events in this study. Larger sample study will be needed to examine the relationship between the concentration and events in clinical practice.

Rivaroxaban concentrations in acute stroke patients with different dosage forms.

BACKGROUND: The crushed-tablet rivaroxaban concentration has been previously reported to be lower than the non-crushed concentration. However, the rivaroxaban concentration of fine granules has not yet been investigated. The anticoagulation intensity of rivaroxaban with fine granules, tablets, and crushed tablets was compared in acute stroke patients to assess the efficacy of each form. METHODS AND FINDINGS: Hospitalized patients over 75 years old with acute stroke who started taking rivaroxaban from April 2012 to September 2017 were included. Blood samples were drawn just before and 4 hours after taking rivaroxaban on a median of 5 days after treatment initiation for concentration measurements (C0h, C4h) based on an anti-factor Xa chromogenic assay. Of 114 patients (49 female, 83±5 years old), 97 had ischemic strokes, 9 had transient ischemic attacks, and 8 had intracerebral hemorrhages. Rivaroxaban was administered a median of 7 days after onset. Of these, 38 patients were given the 15 mg dose, and 76 were given the 10 mg dose. In the 15 mg dose group, C0h was significantly higher in the fine granule group than in the crushed tablet group, with no significant difference compared to the tablet group [C0h: 27.6±6.8 vs 4.0±4.1 (P = 0.01) vs. 33.3±25.2 ng/ml, (P = 0.51), respectively], as was C4h [223.0±66.6 vs 103.0±79.5 (P = 0.02) vs. 229.5±121.6 ng/ml (P = 0.88)]. In the 10 mg dose group, C0h was significantly higher in the fine granule group than in the crushed tablet group and comparable to that in the tablet group [23.2±7.9 vs 7.5±6.2 (P<0.01) vs 19.0±15.8 ng/ml, (P = 0.35)], as was C4h [150.7±85.4 vs 85.1±46.8 (P<0.01) vs 189.8±92.7 ng/ml (P = 0.18)]. CONCLUSIONS: The rivaroxaban concentration with fine granules was consistent with that in the tablet group and higher than that in the crushed tablet group.

Usefulness of Transesophageal Echocardiography for Predicting Covert Paroxysmal Atrial Fibrillation in Patients with Embolic Stroke of Undetermined Source.

BACKGROUND: Covert paroxysmal atrial fibrillation (CPAF) is a major cause of embolic stroke of undetermined source (ESUS). However, detecting PAF during hospitalization in these patients is difficult. OBJECTIVES: This study aimed to determine whether findings of transesophageal echocardiography (TEE) during hospitalization are associated with later detection of PAF in patients with ESUS. METHOD: We retrospectively studied 348 patients with ESUS who were admitted to our hospital within 1 week of onset. These patients met the criteria of ESUS, underwent TEE during hospitalization, and were followed up for at least 1 year. RESULTS: We found PAF in 35 (10.0%) patients. In patients with PAF, spontaneous echo contrast (SEC) and low left atrial appendage flow (LAAF) by TEE and enlargement of the left atrial dimension (LAD) by transthoracic echocardiography were identified more frequently compared with those who did not have PAF. In multivariate analysis, SEC and an LAD ≥42 mm were independently associated with later detection of PAF (p < 0.05). An association of LAAF <46.9 cm/s and PAF was marginal (p = 0.09). The specificity of the combined finding of SEC and/or LAAF with that of LAD increased up to 90%, while that of LAD alone was 70%. CONCLUSIONS: The findings of TEE during hospitalization may be useful for identifying patients at increased risk of CPAF in patients with ESUS.

Outcome Prediction in Acute Stroke Patients by Continuous Glucose Monitoring.

BACKGROUND: The purpose of this study was to examine the relationships between glucose parameters obtained by continuous glucose monitoring and clinical outcomes in acute stroke patients. METHODS AND RESULTS: Consecutive patients with acute ischemic stroke or intracerebral hemorrhage within 24 hours after onset were included. A continuous glucose monitoring device (iPro2) was attached for the initial 72 hours after emergent admission. Eight glucose parameters were obtained from continuous glucose monitoring: maximum, minimum, mean, and SD of blood glucose levels, as well as area under the curve more than 8 mmol/L of blood glucose, distribution time more than 8 mmol/L of blood glucose, coefficient of variation (%CV), and presence of time less than 4 mmol/L over 72 hours. The primary outcome measure was death or dependency at 3 months (modified Rankin Scale score ≥3). One hundred patients with acute ischemic stroke (n=58) or intracerebral hemorrhage (n=42) were included. Blood glucose levels varied between 5.2±1.4 and 11.4±3.2 mmol/L over 72 hours, with area under the curve more than 8 mmol/L of blood glucose of 0.7±1.4 min×mmol/L, distribution time more than 8 mmol/L of blood glucose of 31.7±32.7%, coefficient of variation of 15.5±5.4%, and presence of hypoglycemia in 20% of overall patients. Mean glucose level (adjusted odds ratio, 1.60, 95% confidence interval, 1.12-2.28/1 mmol/L), area under the curve more than 8 mmol/L of blood glucose (2.13, 1.12-4.02/1 min×mmol/L), and distribution time more than 8 mmol/L of blood glucose (1.25, 1.05-1.50/10%) were related to death or dependency for overall patients, as well as for acute ischemic stroke patients (2.05, 1.15-3.65; 2.38, 1.04-5.44; 1.85, 1.10-3.10, respectively). CONCLUSIONS: High mean glucose levels, distribution time more than 8 mmol/L of blood glucose, and areas under the curve more than 8 mmol/L of blood glucose during the initial 72 hours of acute stroke were associated with death or dependency at 3 months.

Assessment of lower limb ischemia with measurement of skin perfusion pressure in patients on hemodialysis.

Measurement of skin perfusion pressure (SPP) using laser Doppler has become available for the assessment of peripheral arterial disease. We studied whether measurements of SPP can be used to identify hemodialyzed patients with peripheral arterial disease by comparing it with measurements of the ankle brachial pressure index (ABI). The ABI at rest and the SPP in the foot were measured in 59 Japanese hemodialyzed patients (118 limbs). Twenty-one patients had diabetes mellitus. Five had intermittent claudication; however, 20 patients were accompanied by other exertional leg symptoms. The SPP could not be measured in three limbs because of involuntary movement due to previous stroke or restless leg syndrome. The SPP was correlated with the ABI. Depending upon these results of the ABI, the 114 limbs from which both the ABI and the SPP could measured were divided into three groups: (A) ABI > or = 1.3, (B) 0.9 < or = ABI < 1.3, and (C) ABI < 0.9. The average SPP of group C was significantly decreased among the three groups. All subjects of the three groups were divided into an extra two groups according to the presence of diabetes (non-diabetes groups, -I; diabetes groups, -II). The average SPP of group B-II was significantly decreased compared with those of group B-I. The SPP measurement is a noninvasive, useful screening method for limb ischemia that can be applied to exercise tolerance limited patients. The SPP measurements are expected to be useful for the evaluation of limb ischemia in hemodialyzed patients at risk.

Risk factors for post-stroke seizure recurrence after the first episode.

PURPOSE: Seizure is a common complication after stroke. However, the clinical characteristics, treatment, and recurrence rates in patients with the first episode of post-stroke seizure remain unclarified. The aim of this study was to identify the predictors of seizure recurrence in those patients. METHOD: We retrospectively identified patients admitted to our hospital between July 2010 and June 2014 and followed-up until June 2015 because of the first episode of post-stroke seizure. We classified post-stroke seizure as early (within one week after stroke) or late (in the second week or later). We compared the baseline clinical characteristics and treatment between the groups and investigated the factors that determined seizure recurrence by Cox proportional hazards model. RESULTS: A total of 153 patients (84 men; mean age, 73.7±12.3years; 73 hemorrhagic and 80 ischemic strokes; 63 early and 90 late seizure) were included. Compared with the late seizure group, the early seizure group more frequently manifested with status epilepticus; tended to less often undergo stereotactic aspiration of hematoma; and less frequently used anti-epileptic drugs. During the observation period (median 364days, IQR 124-680days), 40 patients were lost to follow-up; subsequently, 113 patients were included in the analysis. The early seizure group had lower survival and seizure recurrence rates than the late seizure group. The factors significantly associated with seizure recurrence were presence of status epilepticus in the early group (HR 4.75, 95% CI 1.28-17.62) and younger age in the late seizure group (HR 0.95, 95% CI 0.93-0.99). CONCLUSIONS: In patients with post-stroke seizure, status epilepticus and younger age were the predictors of recurrence after early and late seizure, respectively.

Prothrombin complex concentrate administration for bleeding associated with non-vitamin K antagonist oral anticoagulants: The SAMURAI-NVAF study.

BACKGROUND: Antidotes appropriate for non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) are not yet in widespread clinical use. Efficacy of prothrombin complex concentrate (PCC) in NOAC-associated bleeding remains unclarified. METHODS: Ten NOAC users (4 women, median 74years old) who developed major bleeding and received PCC were prospectively enrolled. Eight single-center NOAC users (0 women, median 74years old) with intracerebral hemorrhage, who over the same period did not receive PCC, were studied for comparison. RESULTS: Of the 10 PCC-treated patients, 8 developed intracerebral hemorrhage, 1 developed subdural hematoma, and another developed gastrointestinal bleeding. The median size of intracerebral hemorrhage was 8mL, relatively lower than the reported size for patients without NOACs. Patients received a median of 1000IU or 16IU/kg of PCC. Before and 1h after PCC administration, the median PT-INR changed from 1.41 to 1.09 (p<0.05) and median aPTT changed from 35.4 to 38.0s (p=0.39). Five patients developed intracranial hematoma expansion and 4 required surgical hematoma evacuation. No symptomatic thrombotic events occurred in either group, no participants died, and 2 participants from each group were independent. CONCLUSIONS: Ten NOAC users developed major bleeding and were given relatively low doses of PCC. The effect of PCC on early cessation of bleeding was unclear, while the therapy did not trigger thromboembolic complications.

Subarachnoid hemorrhage not due to ruptured aneurysm in moyamoya disease.

A patient with moyamoya disease presenting with subarachnoid hemorrhage (SAH) is reported. A 38-year-old Japanese woman developed a sudden onset headache and nausea during hospitalization for a cerebral infarct in the right frontal lobe. CT scan showed SAH in the left frontal sulci. Cerebral angiogram showed stenosis of the distal bilateral internal carotid arteries with moyamoya vessels, and significant transdural anastamoses from the left external carotid artery to cortical arteries on the left frontal cortex. The patient was kept normotensive and underwent a right-sided surgical revascularization procedure, remaining well for three years. SAH not due to ruptured aneurysm in moyamoya disease is rare. The cause of the SAH was thought to be disruption of the transdural anastomotic vessels. Recognition of these fragile vessels in moyamoya disease is essential.

Intracranial subdural hematomas with elevated rivaroxaban concentration and subsequently detected spinal subdural hematoma: A case report.

A 79-year-old lean man with a height of 157cm and weight of 42kg (body mass index, 17.2kg/m(2)) receiving rivaroxaban developed an intracranial subdural hematoma and was treated conservatively. Because he had a reduced creatinine clearance of 44mL/min, his dosage of rivaroxaban was reduced from 15 to 10mg daily according to official Japanese prescribing information. However, he developed bilateral intracranial subdural hematomas 2weeks later. Plasma rivaroxaban concentration on anti-factor Xa chromogenic assay was elevated at 301ng/mL, suggesting excessive accumulation. He underwent burr hole drainage and resumed anticoagulation with warfarin. Subsequently, he developed a lumbosacral hematoma. He was treated conservatively and discharged without neurological sequelae. The main cause of the increased concentration of rivaroxaban was believed to be his older age and low body weight. The etiology of the spinal hematoma was suspected to be the migration of intracranial hematoma to the spinal subdural space.