[Evaluation of cerebral hemodynamics using arterial spin labeling perfusion MR imaging in a patient with cervical internal carotid artery vasospasm].

57-year-old woman with sequelae of cerebral infarction was admitted to our hospital because her left-sided hemiparesis was worsened. The right internal carotid artery (ICA) was not visualized by carotid duplex sonography and brain MRA. Arterial spin labeling (ASL) perfusion MR images showed reduced signals in the bilateral ICA territories at post labeling delay 1,525 ms. Her neurological symptoms improved on the day after hospitalization. On day 3, the bilateral ICAs were well visualized on MRA, while cerebral perfusion in the ICA territories appeared to be normalized on ASL. We diagnosed cervical ICA vasospasm, based on the findings of cervical MRA and cerebral angiography. Three months later, the recurrence of ICA vasospasm occurred. ASL was useful for the serial non-invasive evaluation of cerebral hemodynamics from the onset to improvement in a patient with ICA vasospasm.

A Case of Huge Scrotal Hematoma during Mechanical Thrombectomy.

Objective: We report a case of huge scrotal hematoma during emergency mechanical thrombectomy. Case Presentation: An 85-year-old man presented with sudden aphasia and right-sided hemiplegia. He was diagnosed with cerebral infarction due to left M1 occlusion and underwent an emergency mechanical thrombectomy. The treatment was completed with full recanalization, but when replacing the long sheath in the right femoral artery with a short sheath, the patient flexed his leg. The sheath could not be replaced, resulting in a massive scrotal hematoma. Shortly after, the patient went into cardiopulmonary arrest but recovered spontaneous circulation after cardiopulmonary resuscitation. The puncture site was treated hemostatically with manual compression, and the scrotal hematoma was not enlarged. He was transferred to another hospital with a modified Rankin Scale score of 5. Conclusion: Scrotal hematoma is a rare but potentially fatal puncture site complication that should be considered during neuro-endovascular treatment.

Multiple Thrombectomies for Cerebral and Coronary Artery Occlusion in Trousseau Syndrome.

Objective: Trousseau syndrome (TS) is a condition of systemic thrombosis generally associated with an underlying malignancy. An ischemic stroke is a representative thrombotic event. Thrombectomy is a useful procedure for the treatment of cerebral large vessel occlusion, and anticoagulation therapy is the main preventive treatment for TS. This case report describes a woman with terminal pancreatic tumor presenting with repeated occlusions of cerebral and coronary arteries necessitating multiple thrombectomies. Case Presentation: A 67-year-old woman was admitted to our hospital with severe right hemiplegia and global aphasia. MRI revealed left M1 occlusion; therefore, a thrombectomy was performed. Her symptoms recovered completely. Body contrast CT revealed pancreatic cancer with multiple metastases, and she was diagnosed with TS. On day 4 after thrombectomy, the same neurological symptoms occurred and re-occlusion of the left M1 was confirmed. Endothelial injury was suspected, and thrombectomy was repeated. Despite continuing anticoagulation therapy, the coronary artery was occluded and she underwent percutaneous coronary intervention on day 13. To treat the primary pancreatic lesion, she was transferred to the Surgery unit on day 20. Conclusion: Hypercoagulability associated with TS and endothelial damage due to rough procedure resulted in repeated vessel occlusions in this case. Careful thrombectomy and anticoagulation therapy with strict monitoring are needed in TS patients.

Left Atrial Size and Ischemic Events after Ischemic Stroke or Transient Ischemic Attack in Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: The present study aimed to clarify the association between left atrial (LA) size and ischemic events after ischemic stroke or transient ischemic attack (TIA) in patients with nonvalvular atrial fibrillation (NVAF). METHODS: Acute ischemic stroke or TIA patients with NVAF were enrolled. LA size was classified into normal LA size, mild LA enlargement (LAE), moderate LAE, and severe LAE. The ischemic event was defined as ischemic stroke, TIA, carotid endarterectomy, carotid artery stenting, acute coronary syndrome or percutaneous coronary intervention, systemic embolism, aortic aneurysm rupture or dissection, peripheral artery disease requiring hospitalization, or venous thromboembolism. RESULTS: A total of 1,043 patients (mean age, 78 years; 450 women) including 1,002 ischemic stroke and 41 TIA were analyzed. Of these, 351 patients (34%) had normal LA size, 298 (29%) had mild LAE, 198 (19%) had moderate LAE, and the remaining 196 (19%) had severe LAE. The median follow-up duration was 2.0 years (interquartile range, 0.9-2.1). During follow-up, 117 patients (11%) developed at least one ischemic event. The incidence rate of total ischemic events increased with increasing LA size. Severe LAE was independently associated with increased risk of ischemic events compared with normal LA size (multivariable-adjusted hazard ratio, 1.75; 95% confidence interval, 1.02-3.00). CONCLUSION: Severe LAE was associated with increased risk of ischemic events after ischemic stroke or TIA in patients with NVAF.

Comparison of pseudocontinuous arterial spin labeling perfusion MR images and time-of-flight MR angiography in the detection of periictal hyperperfusion.

BACKGROUND: Magnetic resonance imaging (MRI), including perfusion MRI with three-dimensional pseudocontinuous arterial spin labeling (ASL) and diffusion-weighted imaging (DWI), are applied in the periictal (including ictal and postictal) detection of circulatory and metabolic consequences associated with epilepsy. Our previous report revealed that periictal hyperperfusion can firstly be detected on ASL, and cortical hyperintensity of cytotoxic edema secondarily obtained on DWI from an epileptically activated cortex. Although magnetic resonance angiography (MRA) using three-dimensional time-of-flight is widely used to evaluate arterial circulation, few MRA studies have investigated the detection of periictal hyperperfusion. METHODS: To compare the ability of ASL and MRA to detect the periictal hyperperfusion on visual inspection, we retrospectively selected 23 patients who underwent ASL and MRA examination on both periictal and interictal periods. Patients were divided into the following three groups according to periictal ASL/DWI findings: positive ASL and DWI findings (n = 13, ASL+/DWI+ group), positive ASL and negative DWI findings (n = 5, ASL+/DWI- group), and negative ASL and DWI findings (n = 5, ASL-/DWI- group). RESULTS: Periictal hyperperfusion on MRA was detected in 6 out of 13 patients (46.2%) in the ASL+/DWI+ group, but not in all patients in the ASL+/DWI- and ASL-/DWI- groups. Furthermore, in 5 out of these 6 patients, the diagnosis of periictal MRA hyperperfusion could not be made without referring to interictal MRA and/or periictal ASL findings, because the periictal MRA findings were so minute. CONCLUSION: The minimum requirement for the development of periictal MRA hyperperfusion is that its epileptic event is intense enough to induce the uncoupling between metabolism and circulation, with the induction of glutamate excitotoxity, and severe cytotoxic edema on DWI. ASL is vastly superior to MRA in the detection of periictal hyperperfusion.

Ischemic Stroke despite Oral Anticoagulant Therapy in Patients with Atrial Fibrillation.

OBJECTIVE: It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed. METHODS: We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OACprior ) with those without prior oral anticoagulation (OACnaive ). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OACchanged ) with those who continued the same anticoagulation as secondary prevention (OACunchanged ). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71-84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2-12]). The median CHA2 DS2 -Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OACprior (n = 1,195) and OACnaive (n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OACprior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OACchanged (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OACunchanged (n = 585). INTERPRETATION: Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA2 DS2 -Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group. ANN NEUROL 2020.

Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation.

OBJECTIVE: We compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia. METHODS: We conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia (<3 months before starting oral anticoagulation) and a minimum follow-up of 3 months. We analyzed the association between type of anticoagulation (DOAC versus VKA) with the composite primary endpoint (recurrent ischemic stroke [AIS], intracerebral hemorrhage [ICH], or mortality) using mixed-effects Cox proportional hazards regression models; we calculated adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs). RESULTS: We included 4,912 patients (median age, 78 years [interquartile range {IQR}, 71-84]; 2,331 [47.5%] women; median National Institute of Health Stroke Severity Scale at onset, 5 [IQR, 2-12]); 2,256 (45.9%) patients received VKAs and 2,656 (54.1%) DOACs. Median time from index event to starting oral anticoagulation was 5 days (IQR, 2-14) for VKAs and 5 days (IQR, 2-11) for DOACs (p = 0.53). There were 262 acute ischemic strokes (AISs; 4.4%/year), 71 intracranial hemorrrhages (ICHs; 1.2%/year), and 439 deaths (7.4%/year) during the total follow-up of 5,970 patient-years. Compared to VKAs, DOAC treatment was associated with reduced risks of the composite endpoint (HR, 0.82; 95% CI, 0.67-1.00; p = 0.05) and ICH (HR, 0.42; 95% CI, 0.24-0.71; p < 0.01); we found no differences for the risk of recurrent AIS (HR, 0.91; 95% CI, 0.70-1.19; p = 0.5) and mortality (HR, 0.83; 95% CI, 0.68-1.03; p = 0.09). INTERPRETATION: DOAC treatment commenced early after recent cerebral ischemia related to AF was associated with reduced risk of poor clinical outcomes compared to VKA, mainly attributed to lower risks of ICH. ANN NEUROL 2019;85:823-834.

Subtraction of arterial spin-labeling magnetic resonance perfusion images acquired at dual post-labeling delay: Potential for evaluating cerebral hyperperfusion syndrome following carotid endarterectomy.

Arterial spin-labeling magnetic resonance perfusion imaging is a promising tool for the diagnosis of cerebral hyperperfusion syndrome after carotid endarterectomy. However, arterial spin-labeling with a single post-labeling delay has been reported to show a higher incidence of increased arterial spin-labeling signals in the bilateral hemisphere, probably due to a shortening of the arterial transit time or an arterial transit artifact caused by intravascular stagnant magnetically-labeled spin. To overcome these shortcomings, we used two post-labeling delay settings (1.0 and 1.5 s) in 8 patients who had undergone carotid endarterectomy. In addition, we created a subtraction image between the mean perfusion maps at post-labeling delays of 1.0 and 1.5 s. This also decreased arterial transit artifacts, as these appeared in nearly the same configuration in both post-labeling delay settings. In all eight cases examined, increased arterial spin-labeling signals were observed bilaterally on both dual post-labeling delay settings. Subtraction images revealed that these increased signals were attributable to arterial transit artifacts in seven cases. However, in one patient who developed clinical symptoms, the subtraction method demonstrated post-carotid endarterectomy hyperperfusion. This preliminary study demonstrates that the subtraction method might decrease arterial transit artifacts and yield a map that can better represent true perfusion, thus enabling the detection of post-carotid endarterectomy hyperperfusion.

Prior Anticoagulation and Short- or Long-Term Clinical Outcomes in Ischemic Stroke or Transient Ischemic Attack Patients With Nonvalvular Atrial Fibrillation.

Background We aimed to clarify associations between prior anticoagulation and short- or long-term clinical outcomes in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Methods and Results A total of 1189 ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation who were hospitalized within 7 days after onset were analyzed. Of these, 813 patients (68.4%) received no prior anticoagulation, 310 (26.1%) received prior warfarin treatment with an international normalized ratio ( INR ) <2 on admission, 28 (2.4%) received prior warfarin treatment with an INR ≥2 on admission, and the remaining 38 (3.2%) received prior direct oral anticoagulant treatment. Prior warfarin treatment was associated with a lower risk of death or disability at 3 months compared with no prior anticoagulation ( INR <2: adjusted odds ratio: 0.58; 95% CI, 0.42-0.81; P=0.001; INR ≥2: adjusted odds ratio: 0.40; 95% CI, 0.16-0.97; P=0.043) but was not associated with a lower risk of death or disability at 2 years. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years compared with no prior anticoagulation (adjusted hazard ratio: 2.94; 95% CI, 1.20-6.15; P=0.021). Conclusions Prior warfarin treatment was associated with a lower risk of death or disability at 3 months but was not associated with a lower risk of death or disability at 2 years in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01581502.

Hemodynamic state of periictal hyperperfusion revealed by arterial spin-labeling perfusion MR images with dual postlabeling delay.

BACKGROUND: Magnetic resonance imaging (MRI), including perfusion MRI with arterial spin labeling (ASL) and diffusion-weighted imaging (DWI), are applied in the periictal detection of circulatory and metabolic consequences associated with epilepsy. Although previous report revealed that prolonged ictal hyperperfusion on ASL can be firstly detected and cortical hyperintensity of cytotoxic edema on DWI secondarily obtained from an epileptically activated cortex, the hemodynamic state of the periictal hyperperfusion has not been fully demonstrated. METHODS STUDY-1: We retrospectively analyzed the relationship between seizure manifestations and the development of periictal MRI findings, in Case 1 with symptomatic partial epilepsy, who underwent repeated periictal ASL/DWI examination for three epileptic ictuses (one examination for each ictus). Study-2: We evaluated the hemodynamic state of periictal hyperperfusion with the ASL technique using a dual postlabeling delay (PLD) of 1.5 and 2.5 s in nine patients, according to the presence or absence of the localized epileptogenic lesion (EL) on conventional 3 T-MRI, who were divided into Group EL+ (six patients) and Group EL- (three patients). RESULTS: Study-1 confirmed that the stratified representation of the periictal MRI findings depends on the time interval between the ictal cessation and MRI examination in addition to the magnitude and duration of the epileptic activity. In Study-2, two types of periictal hyperperfusion were noted. In all six Group EL+ patients, periictal ASL findings showed "fast flow type". Markedly increased ASL signals were noted at the epileptically activated cortex, having a tight topographical relationship with EL, on ASL with a PLD of 1.5 s, which is decreased on ASL with a PLD of 2.5 s. In all three Group EL- patients, periictal ASL findings showed "gradual flow type", which is characterized by gradual signal increase of the epileptically activated cortex on ASL with a PLD of 1.5 and 2.5 s. CONCLUSION: We confirmed that ASL hyperperfusion is superior to DWI in the periictal detection of epileptic events. ASL with dual PLD offers the ability to document two types of hemodynamics of periictal hyperperfusion.

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.

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.

Associations between Pre-Admission Risk Scores and Two-Year Clinical Outcomes in Ischemic Stroke or Transient Ischemic Attack Patients with Non-Valvular Atrial Fibrillation.

BACKGROUND: We aimed to clarify associations between pre-admission risk scores (CHADS2, CHA2DS2-VASc, and HAS-BLED) and 2-year clinical outcomes in ischemic stroke or transient ischemic attack (TIA) patients with non-valvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry. METHODS: From 18 Japanese stroke centers, ischemic stroke or TIA patients with NVAF hospitalized within 7 days after onset were enrolled. Outcome measures were defined as death/disability (modified Rankin Scale score ≥3) at 2 years, 2-year mortality, and ischemic or hemorrhagic events within 2 years. RESULTS: A total of 1,192 patients with NVAF (527 women; mean age, 78 ± 10 years), including 1,141 ischemic stroke and 51 TIA, were analyzed. Rates of death/disability, mortality, and ischemic or hemorrhagic events increased significantly with increasing pre-admission CHADS2 (p for trend <0.001 for death/disability and mortality, p for trend = 0.024 for events), CHA2DS2-VASc (p for trend <0.001 for all), and HAS-BLED (p for trend = 0.004 for death/disability, p for trend <0.001 for mortality, p for trend = 0.024 for events) scores. Pre-admission CHADS2 (OR per 1 point, 1.52; 95% CI 1.35-1.71; p <0.001 for death/disability; hazard ratio (HR) per 1 point, 1.23; 95% CI 1.12-1.35; p <0.001 for mortality; HR per 1 point, 1.14; 95% CI 1.02-1.26; p = 0.016 for events), CHA2DS2-VASc (1.55, 1.41-1.72, p < 0.001; 1.21, 1.12-1.30, p < 0.001; 1.17, 1.07-1.27, p < 0.001; respectively), and HAS-BLED (1.33, 1.17-1.52, p < 0.001; 1.23, 1.10-1.38, p < 0.001; 1.18, 1.05-1.34, p = 0.008; respectively) scores were independently associated with all outcome measures. CONCLUSIONS: In ischemic stroke or TIA patients with NVAF, all pre-admission risk scores were independently associated with death/disability at 2 years and 2-year mortality, as well as ischemic or hemorrhagic events within 2 years.

[Ruptured Dissecting Aneurysm of the Fenestrated Vertebral Artery:A Case Report].

Fenestration of a vertebral artery(VA)is a rare anomaly that has occasionally been associated with the formation of saccular aneurysms, whereas dissection of a limb of the fenestrated artery is an extremely rare occurrence. We report the case of a ruptured dissecting aneurysm of a fenestrated VA. A 56-year-old man presented with acute-onset headache followed by respiratory failure. Computed tomography(CT)revealed diffuse subarachnoid hemorrhage, and CT angiography(CTA)demonstrated fenestration of the left VA and a fusiform aneurysm of the dorsolateral limb of the fenestrated VA. CT after injection of contrast medium revealed dissection of a limb of the fenestrated VA. A comparison of the 3-dimensional digital subtraction angiogram obtained 2 days later with the initial CTA showed that the dissecting aneurysm had shrunk. Coil embolization of the dissecting limb of the fenestrated VA was achieved, and the patient was discharged without neurologic deficit. Further advancements in neuroimaging modalities will provide more opportunities to treat dissecting aneurysms of fenestrated VAs. The relevant clinical characteristics of VA fenestration and the treatment options for a dissecting aneurysm of a limb of the fenestrated VA are also discussed in this report.

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.

Optimal perioperative management of antithrombotic agents in patients with chronic subdural hematoma.

OBJECTIVE: The use of antithrombotic agents such as anticoagulants and antiplatelet agents is widespread, and the opportunities to treat patients with chronic subdural hematoma (CSDH) under antithrombotic therapy are growing. However, whether antithrombotic therapy contributes to postoperative complications and recurrences of CSDH and how these agents should be managed in the surgical treatment of CSDH remains unclear. METHODS: We retrospectively analyzed 150 consecutive patients with CSDH who underwent neurosurgical interventions at Kyushu Rosai Hospital from 2011 to 2015 and followed them for more than 3 months. RESULTS: Of the 150 study patients, 44 received antithrombotic therapy. All anticoagulants and 76% of the antiplatelet agents were discontinued before surgical treatment of CSDH and resumed within 1 week except in 4 patients whose treatment was terminated and 7 patients who developed postoperative complications or underwent reoperations before resumption of these agents. Postoperative hemorrhagic complications associated with surgical treatment of CSDH occurred in 8 patients (5.3%), and there was no significant difference in the incidence of these complications between patients with and without antithrombotic therapy (6.8% vs. 4.7%, respectively; p=0.90). Postoperative thromboembolic complications occurred in 5 patients (5.4%), including 4 patients with antithrombotic therapy; these complications developed before resumption of antithrombotic agents in 2 patients. There was a significant difference in the incidence of postoperative thromboembolic complications between patients with and without antithrombotic therapy (9.1% vs. 0.9%, respectively; p=0.04). There were no significant differences in the incidence of radiographic deterioration or reoperation of ipsilateral or contralateral hematomas between patients with and without antithrombotic therapy after surgical treatment of unilateral CSDH. CONCLUSION: A history of antithrombotic therapy was significantly correlated with the incidence of postoperative thromboembolic complications in patients with CSDH. Antithrombotic agents should be resumed as soon as possible when no hemorrhagic complication is confirmed after neurosurgical intervention for CSDH.

Higher Risk of Ischemic Events in Secondary Prevention for Patients With Persistent Than Those With Paroxysmal Atrial Fibrillation.

BACKGROUND AND PURPOSE: The discrimination between paroxysmal and sustained (persistent or permanent) atrial fibrillation (AF) has not been considered in the approach to secondary stroke prevention. We aimed to assess the differences in clinical outcomes between mostly anticoagulated patients with sustained and paroxysmal AF who had previous ischemic stroke or transient ischemic attack. METHODS: Using data from 1192 nonvalvular AF patients with acute ischemic stroke or transient ischemic attack who were registered in the SAMURAI-NVAF study (Stroke Management With Urgent Risk-Factor Assessment and Improvement-Nonvalvular AF; a prospective, multicenter, observational study), we divided patients into those with paroxysmal AF and those with sustained AF. We compared clinical outcomes between the 2 groups. RESULTS: The median follow-up period was 1.8 (interquartile range, 0.93-2.0) years. Of the 1192 patients, 758 (336 women; 77.9±9.9 years old) and 434 (191 women; 77.3±10.0 years old) were assigned to the sustained AF group and paroxysmal AF groups, respectively. After adjusting for sex, age, previous anticoagulation, and initial National Institutes of Health Stroke Scale score, sustained AF was negatively associated with 3-month independence (multivariable-adjusted odds ratio, 0.61; 95% confidence interval, 0.43-0.87; P=0.006). The annual rate of stroke or systemic embolism was 8.3 and 4.6 per 100 person-years, respectively (multivariable-adjusted hazard ratio, 1.95; 95% confidence interval, 1.26-3.14) and that of major bleeding events was 3.4 and 3.1, respectively (hazard ratio, 1.13; 95% confidence interval, 0.63-2.08). CONCLUSIONS: Among patients with previous ischemic stroke or transient ischemic attack, those with sustained AF had a higher risk of stroke or systemic embolism compared with those with paroxysmal AF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01581502.

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.

Optimal Peak Systolic Velocity Thresholds for Predicting Internal Carotid Artery Stenosis Greater than or Equal to 50%, 60%, 70%, and 80%.

BACKGROUND: We aimed to determine the optimal peak systolic velocity (PSV) thresholds for predicting ≥50%, ≥60%, ≥70%, and ≥80% internal carotid artery (ICA) stenosis. METHODS: Patients who underwent both carotid ultrasonography and cerebral angiography during hospitalization were consecutively and retrospectively enrolled. The degree of ICA stenosis was calculated using the North American Symptomatic Carotid Endarterectomy Trial method on cerebral angiography. The optimal PSV thresholds for predicting ≥50%, ≥60%, ≥70%, and ≥80% ICA stenosis were determined using receiver operating characteristic curves and the Youden index. RESULTS: A total of 127 ICAs were analyzed. The optimal PSV thresholds for predicting ≥50%, ≥60%, ≥70%, and ≥80% ICA stenosis were 130 cm/s (sensitivity, 95%; specificity, 85%; positive predictive value [PPV], 75%; negative predictive value [NPV], 97%; overall accuracy, 88%), 160 cm/s (sensitivity, 91%; specificity, 94%; PPV, 83%; NPV, 97%; overall accuracy, 93%), 200 cm/s (sensitivity, 96%; specificity, 95%; PPV, 83%; NPV, 99%; overall accuracy, 95%), and 270 cm/s (sensitivity, 89%; specificity, 94%; PPV, 74%; NPV, 98%; overall accuracy, 94%), respectively. CONCLUSIONS: The optimal PSV thresholds for predicting ≥50%, ≥60%, ≥70%, and ≥80% ICA stenosis were 130 cm/s, 160 cm/s, 200 cm/s, and 270 cm/s, respectively. All of them had high diagnostic accuracies.

Impact of renal function deterioration on adverse events during anticoagulation therapy using non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

Renal function is crucial for patients with non-valvular atrial fibrillation (NVAF) using non-vitamin K antagonist oral anticoagulants (NOAC). The incidence of renal function deterioration during anticoagulation therapy and its impact of adverse events are unknown. In 807 consecutive NVAF patients treated with NOAC and with estimated creatinine clearance (eCCr) ≥ 50 ml/min (mean age 68 ± 11 years, mean CHADS2 score = 1.8 ± 1.4, CHA2DS2-VASc score = 2.8 ± 1.8, HAS-BLED score = 1.7 ± 1.1), we analyzed the time course of renal function and clinical outcomes, and compared these with the data of general Japanese inhabitants from the Suita Study (n = 2140). Of the 807 patients, 751 (93 %) maintained eCCr ≥ 50 ml/min (group A) whereas the remaining 56 (7 %) fell into the eCCr < 50 ml/min (group B) during the 382 ± 288 days of follow-up. Multivariate logistic regression analysis revealed that advanced age, lower body weight, and congestive heart failure were independent predictors for renal function deterioration in patients with eCCr ≥ 50 ml/min at baseline. Major and/or minor bleedings were more commonly observed in group B than in group A (21 vs. 8 %; P = 0.0004). The CHADS2, CHA2DS2-VASc, and HAS-BLED scores were also significant predictors of renal function deterioration (P < 0.0001). The incidences of renal function deterioration were 1.4, 3.4, 10.5 and 11.7 % in patients with CHADS2 score of 0, 1, 2 and ≥3, respectively. As to CHA2DS2-VASc score, renal function deterioration occurred in 0, 1.7, 9.8 and 15.0 % with a score of 0, 1-2, 3-4 and ≥5, respectively. In the Suita Study of the general population, on the other hand, 122 of 2140 participants with eCCr ≥ 50 ml/min at baseline (5.7 %) fell into the eCCr < 50 ml/min during about 2 years. The incidence of renal function deterioration increased with the CHADS2 score in the general population as well as in our patients. Renal function deterioration was not uncommon and was associated with more frequent adverse events including major bleeding in NVAF patients with anticoagulation therapy. CHADS2, CHA2DS2-VASc, and HAS-BLED scores may be useful as an index of predicting renal function deterioration.