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.

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.

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.

Serum 1,5-Anhydroglucitol: Risk Factor of Acute Ischemic Stroke and Transient Ischemic Attack in Well-Controlled Diabetes.

BACKGROUND: Serum 1,5-anhydroglucitol (1,5-AG) levels are a measure that provides information on daily glycemic variations. We evaluated whether 1,5-AG could be a possible marker of acute ischemic stroke (AIS) or transient ischemic attacks (TIA) in patients with diabetes mellitus (DM). METHODS: We retrospectively reviewed electronic medical records of 5,294 AIS/TIA patients. Of the 5,294, 1,898 had diabetes and in 1,246, serum 1,5-AG levels were measured (group S). Group S was divided into 2 subgroups: hemoglobin A1c (HbA1c) <7% (S-low) and >7% (S-high). As controls, 394 outpatients with diabetes (group C) without AIS/TIA were likewise divided into subgroups, C-low and C-high according to HbA1c level. In each HbA1c subgroup, the association between serum 1,5-AG (≥14 vs. <14 µg/mL) and stroke was examined using multivariable logistic regression (MLR) with stepwise variable selection. In model 1, the OR and 95% CI was examined adjusted for age and gender. Known risk factors for stroke; hypertension, dyslipidemia, alcohol consumption, smoking, and estimated glomerular filtration rate were included in model 2. RESULTS: Overall, serum 1,5-AG levels were lower in group S than in group C. Serum 1,5-AG levels were low in subgroups S-high and C-high, showing no differences in mean values. However, mean serum 1,5-AG levels in S-low was statistically lower than that in C-low. MLR analysis showed that the OR for low (<14 µg/mL) 1,5-AG for stroke was statistically significant only in well-controlled diabetes (OR [95% CI] 2.19 [1.54-3.10]) in model 1 and (2.26 [1.56-3.28]) model 2. CONCLUSIONS: Low serum 1,5-AG levels could be a possible marker for AIS/TIA risk in patients with well-controlled DM.

Ischemic Stroke Mortality Is More Strongly Associated with Anemia on Admission Than with Underweight Status.

BACKGROUND: Underweight patients have recently been reported as a group with a high risk of poststroke death. Anemia also increases mortality rates in stroke patients. However, the causal associations between body weight and anemia resulting in stroke-related death remain unclear. We examined the association of weight status and hemoglobin levels with 3-month mortality after ischemic stroke. METHODS: The study enrolled all consecutive patients with acute ischemic stroke and no history of stroke admitted to our hospital between January 2010 and December 2013. The patients were categorized into 4 body mass index (BMI) categories (underweight, normal-weight, overweight, and obese). Anemia was evaluated according to the World Health Organization criteria (men, <13 g/dL; women, <12 g/dL). RESULTS: A total of 1733 acute ischemic stroke patients (149 underweight, BMI < 18.5 kg/m2; 1076 normal-weight, BMI = 18.5-24.9 kg/m2; 436 overweight, BMI = 25-29.9 kg/m2; and 72 obese, BMI > 30 kg/m2) were included. Death within 3 months occurred in 65 patients (underweight, 10.1%; normal-weight, 3.4%; overweight, 2.3%; and obese, 5.6%). Compared to nonanemic patients, those with anemia (n = 329, 19.0%) had lower BMI (21.8 kg/m2 versus 23.7 kg/m2, P <.001) and higher mortality rates (9.1% versus 2.5%, P <.001). Underweight status was associated with 3-month mortality after adjusting for age, sex, comorbidities, and initial stroke severity. However, in the models that included laboratory findings, it was anemia status (odds ratio, 2.81; 95% confidence interval, 1.46-5.43), not underweight status, that was independently associated with 3-month mortality. CONCLUSION: Anemia on admission was associated with stroke mortality independent of underweight status.

Vascular Risk Factors and Internal Jugular Venous Flow in Transient Global Amnesia: A Study of 165 Japanese Patients.

BACKGROUND: The etiology of transient global amnesia (TGA) remains unclear. We studied the pathophysiology of TGA in 165 Japanese patients. SUBJECTS AND METHODS: TGA was diagnosed in hospitalized patients from 2004 to 2015. We analyzed clinical characteristics, magnetic resonance imaging findings, and maximum intima-media thickness of the common carotid artery, and the reflux of internal jugular venous (IJV) flow by ultrasonography, and statistically compared patients with TGA with age-matched and sex-matched patients who have had a transient ischemic attack (TIA), small-vessel occlusion (SVO), and normal controls (each group, N = 165). RESULTS: Patients with TGA showed lower prevalence of vascular risk factors than patients with TIA and SVO did. Eleven patients (6.7%) had 2 episodes of TAG, but specific clinical variables could not be recognized in these patients. The maximum intima-media thickness was significantly thinner in TGA (1.1 ± .7 mm) than in SVO (1.6 ± .9 mm; P = .001). The percentages of cases whose IJV flow reflux was increased by Valsalva maneuver showed no difference (P = .573) between TGA (26.0 %) and SVO (29.4%). MR diffusion-weighted imaging yielded small hyperintense signals in the hippocampus in 64 of 90 (71.1%) patients between 24 and 72 hours. Potential precipitating specific factors or events before the attacks could be recognized in 40 cases (24.2%) of 165 patients. CONCLUSION: Arterial ischemia and IJV flow reflux might not contribute to TGA pathophysiology. The vulnerability of the hippocampus to physical or emotional stress might be suspected as an underlying mechanism in some patients with TGA.

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.

Brain Natriuretic Peptide and Particular Left Ventricle Segment Asynergy Associated with Cardioembolic Stroke from Old Myocardial Infarction.

BACKGROUND: It is important to determine the usage of anticoagulants by defining the actual risk of cardioembolic stroke in patients with old myocardial infarction. In the present study, we aimed to more precisely evaluate the risks of each segment associated with cardioembolic stroke using a 16-segment model. The usage of the plasma brain natriuretic peptide (BNP) associated with cardioembolic stroke was also evaluated in comparison with a left ventricle ejection fraction less than 40%. METHODS: There were a total of 190 ischemic stroke patients who had premorbid myocardial infarction. The study included a total of 143 ischemic stroke patients with old myocardial infarction who were available for evaluation and excluded patients with atrial fibrillation or acute myocardial infarction. Their left ventricle wall motion abnormality and the level of plasma BNP at their admission were analyzed. RESULTS: Hypertension and a plasma BNP level of 206.9 pg/mL or higher, determined from the receiver operating characteristic curve, were independently associated with cardioembolic stroke (χ(2) = 35.6, R(2) = .30, P < .001). Adjusting for these factors, statistically independent high risk was observed at the basal-inferior, basal-inferolateral, mid-anterior, mid-anteroseptal, apical-anterior, and apical-septal left ventricles. CONCLUSION: High plasma BNP levels and left ventricular wall motion abnormalities in the segments perfused with left anterior descending coronary artery or right coronary artery show a high risk for cardioembolic stroke in patients with old myocardial infarction. Considering these factors, it could be possible to more precisely define the risk of cardioembolic stroke and to perform appropriate antithrombotic treatments in old myocardial infarction patients.

Effects of Meteorological Conditions on the Risk of Ischemic Stroke Events in Patients Treated with Alteplase--HEWS-tPA.

BACKGROUND: Predicting a day that presents a high risk for the occurrence of ischemic stroke events may enable health professionals to prepare for emergency stroke therapy more properly. We evaluated the association between meteorological conditions and the frequency of ischemic stroke events in Japanese patients. METHODS: Ischemic stroke patients (n = 299) who were treated with alteplase at 9 stroke hospitals in 3 restricted areas were examined. The daily rates of ischemic stroke events were compared with the daily mean thermo-hydrological index (THI), the atmospheric pressure, and the daily changes of these variables for the 6 days preceding an ischemic stroke event using Poisson regression analysis. RESULTS: We trisected onset days based on the THI (low-temperature, intermediate-temperature, and high-temperature), atmospheric pressure (low-pressure, intermediate-pressure, and high-pressure), changes in THI for preceding 6 days from the previous day (cooler, unchanged-temperature, and warmer), and changes in atmospheric pressure (decreased-pressure, unchanged-pressure, and increased-pressure). The frequency of ischemic stroke was significantly higher on low-temperature or high-pressure days (risk ratio, 1.398, P = .022; risk ratio, 1.374, P = .039), on warmer-temperature days, and when atmospheric pressure varied from the day before (P < .05). There were significantly lower risks for ischemic stroke events on cooler-temperature days, and higher risks were associated with a variation in atmospheric pressure 3 days before the onset from 4 days before (P < .05). CONCLUSIONS: There were higher risks for ischemic stroke events associated with low ambient temperature, high atmospheric pressure, increased temperature, and varied atmospheric pressure. Also, atmospheric pressure variation 3 days before may be associated.

Multicenter Study of Intravenous Recombinant Tissue Plasminogen Activator Infusion around Hiroshima, Japan: The Hiroshima Acute Stroke Retrospective and Prospective Registry Study.

OBJECTIVE: Approximately 10 years have passed since intravenous (IV) recombinant tissue plasminogen activator therapy was approved in Japan. The aim of this retrospective study was to identify the effectiveness and safety of IV alteplase therapy with the Japanese original dose around Hiroshima via consideration of the patients' backgrounds, examination findings, and outcomes. METHODS: All consecutive patients with ischemic stroke who received IV alteplase therapy between October 2005 and October 2010 were registered. RESULTS: Four hundred twenty-nine patients with ischemic stroke (172 female [40.1%], mean age 73.7 ± 11.8 years) were registered. The proportion of patients over 75 years old was 51.5% (221 patients). The median National Institutes of Health Stroke Scale (NIHSS) scores at admission were 13 (interquartile range, 9-19), and the NIHSS scores 24 hours after alteplase infusion were 8 (interquartile range, 3-15). The proportion of intracerebral hemorrhage within the initial 36 hours was 20.2% (86 patients). After the multivariate regression analysis, a history of hypertension (odds ratio = 4.14; 95% confidence interval, 1.32-14.79; P = .01) and no recanalization (odds ratio = 10.10; 95% confidence interval, 3.03-39.33; P < .0001) were independently associated with a modified Rankin Scale (mRS) score of 2 or higher at 3 months. Patients over 75 years old were not significantly associated with an intracerebral hemorrhage within the initial 36 hours and an mRS score of 2 or higher at 3 months. CONCLUSIONS: The results of our study demonstrated that IV alteplase therapy with the Japanese original dose was effective and exhibited a safety profile similar to other studies. Moreover, we should not hesitate to IV alteplase therapy simply because of advanced age.

Safety evaluation of substituting clopidogrel for ticlopidine in Japanese patients with ischemic stroke--Hiroshima ticlopidine, clopidogrel safe exchange trial.

BACKGROUND: Clopidogrel is sometimes substituted for ticlopidine when cerebrovascular or cardiovascular patients develop hematologic abnormalities after ticlopidine treatment. However, the adverse event rate after the substitution to clopidogrel remains undetermined. Therefore, in this study, we aimed to define the risk of adverse events after substituting clopidogrel for ticlopidine without a washout period. METHODS: We prospectively enrolled patients older than 20 years who had a history of noncardioembolic strokes, including transient ischemic attacks, were treated with ticlopidine for at least 6 months. This study was conducted from August 26, 2008, when the first patient was enrolled, to January 16, 2012, the date of the last patient examination, at 8 active stroke centers in Hiroshima, Japan. We excluded patients who had severe disabilities, evidence of cardioembolic stroke, or history of a bleeding event. Each patient received clopidogrel (either 50 mg or 75 mg) once a day in place of ticlopidine without a washout period. Follow-up exams were scheduled within 12 months after the medication substitution. The primary end point of this study was adverse events of interest, including clinically significant reduced blood cell counts, hepatic dysfunction, bleeding, and other serious side effects. RESULTS: In this study, 110 patients were enrolled and analyzed in an intent-to-treat manner (modified intent to treat). Within the scheduled follow-up periods, 9 primary end point events were observed in separate patients. The primary end point events were observed at a rate of 8.4% per year (Kaplan-Meier method). At the time of enrolment, 16 patients met the exclusion criteria, of which 8 recovered from their abnormal hematologic results to the institutional normal limit after the substitution of ticlopidine for clopidogrel (57.4% per year). CONCLUSIONS: The adverse event rates after the substitution of ticlopidine for clopidogrel is similar to the adverse event rates of patients who were initially treated with clopidogrel. The substitution of clopidogrel for ticlopidine should be considered for patients who develop hematologic abnormalities from ticlopidine treatment.

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.

[Reversible cerebral vasoconstriction syndrome: a clinical study of 11 cases].

This study reports eleven cases of reversible cerebral vasospasm syndrome (RCVS). Of the 11 patients, two were males and nine were females, with the average age of 47.9 ± 14.1 years. Many of these patients were young. The rates of severe, intractable and pulsative headache, generalized convulsions, and motor hemiparesis were 64%, 27%, and 36%, respectively. As complications of intracerebral lesions in the early stage of disease onset, convexal subarachnoid hemorrhage, lobar intracerebral hemorrhage, and posterior reversible encephalopathy syndrome were observed in 63%, 9%, and 45% of cases, respectively. Cerebral infarction occurred in 45% of cases at around 1-3 weeks after onset. Improvement of cerebral vasoconstriction was recognized in several cases from about the first month of onset. The post-partum period, migraine, transfusion, rapid amelioration for anemia, renal failure, bathing, and cerebrovascular dissection were suspected as disease triggers. Abnormally high blood pressure at onset was confirmed in 55% of cases. It is important to analyze the pathophysiology of RCVS associated with these triggers from the viewpoint of the breakdown of the blood-brain barrier.

[Adult-Onset Neuronal Intranuclear Inclusion Disease in Two Female Siblings].

Neuronal intranuclear inclusion disease (NIID) in two adult siblings (both women, aged 76 and 68 years) is reported on here. The elder sister had a resting tremor and bradykinesia at age 66 years, and treatment with L-DOPA was initiated(L-3, 4-dihydroxyphenylalanine). Three years later, she showed a frozen gait that was associated with the medication wearing off. The clinical manifestations did not improve with the administration of antiparkinson drugs. Six years later, she showed impaired cognitive functions, which had occured gradually, and she began to take donepezil. At age 76, she was diagnosed with NIID based on a skin biopsy. The younger sister exhibited peculiar behaviors at age 62 years, and showed impaired cognitive function 4 years later. At age 68 years, she died because of an accident in the bath tub. In both cases, diffusion-weighted magnetic resonance imaging (DWI) showed high-intensity signals in the U fiber area of the corticomedullary junction. These signals began in the frontal lobe at the initial stages of the disease, and extended to the parietal and temporal lobes at later stages. High-intensity signal areas were detected in the deep white matter in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images in the elder sister. The histological examination via a skin biopsy was useful in diagnosing NIID. (Received August 18, 2016; Accepted December 8, 2016; Published March 1, 2017).

Potential multisystem degeneration in Asidan patients.

OBJECTIVE: To evaluate a potential multisystem involvement of neurodegeneration in Asidan, in addition to cerebellar ataxia and signs of motor neuron disease. METHODS: We compared the new Asidan patients and those identified in previous studies with Parkinson's disease (PD, n=21), and progressive supranuclear palsy (PSP, n=13) patients using 123I-2ß-Carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) dopamine transporter single photon emission computed tomography (DAT-SPECT) and 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy (Asidan, DAT: n=10; MIBG: n=15). RESULTS: Both the PD and PSP groups served as positive controls for DAT decline. The PD and PSP groups served as a positive and negative control, respectively, of MIBG decline in the early phase H/M ratio. Of the Asidan patients, 60.0% showed DAT decline without evident parkinsonian features and 6.7% showed impaired MIBG in only the delayed phase H/M ratio. Combined with a normal range of the early phase H/M ratio, this phenotype was newly named Declined DAT Without Evident Parkinsonism (DWEP). INTERPRETATION: The results of present study including DWEP suggest a wider spectrum of neurodegeneration for extrapyramidal and autonomic systems in Asidan patients than expected, involving cerebellar, motor system and cognitive functioning.

Ability of the Ankle Brachial Index and Brachial-Ankle Pulse Wave Velocity to Predict the 3-Month Outcome in Patients with Non-Cardioembolic Stroke.

AIM: Both the ankle brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) are surrogates for atherosclerosis. In this study, we aimed to evaluate the ability of ABI and baPWV to predict stroke outcome in patients with first-ever non-cardioembolic stroke. METHODS: This study included consecutive patients with first-ever non-cardioembolic stroke admitted within 1 week after onset to Ota Memorial Hospital between January 2011 and December 2013. Baseline characteristics and National Institutes of Health stroke scale scores at admission were noted. ABI and baPWV were evaluated within 5 days of admission. The patients were categorized according to ABI (cut-off 0.9) and baPWV (cut-off 1870 cm/s) determined using the receiver operation curve for poor outcome. Clinical outcomes were defined based on the modified Rankin scale (mRS) scores 3 months after stroke onset as good (0 and 1) or poor (2-6). RESULTS: A total of 861 patients were available for evaluation. ABI ＜0.9 and baPWV ＞1870 cm/s were associated with poor outcome in the univariate analysis (p＜0.001 and p＜0.001, respectively). After adjusting for factors that showed differences between groups, ABI ＜0.9 was associated with poor outcome. Among patients with ABI ≥ 0.9, higher baPWV showed a slight association with poor outcome after adjustment [odds ratio 1.46 (95% CI 0.95-2.27)]. CONCLUSION: Our study suggests that the stroke outcome can be predicted using ABI and to an extent using baPWV when ABI ≥ 0.9 in patients with non-cardioembolic stroke.

Cerebral venous sinus thrombosis in the patient with multiple sclerosis associated with congenital antithrombin deficiency.

We report the case of a 25-year-old man with multiple sclerosis (MS) who had severe headache and unconsciousness. He suffered from optic neuritis that had started at age 6. From the age of 12 years, he had suffered from multiple sclerosis (MS) cerebral lesions that relapsed three times over for 5 years. At age 25, he showed a new lesion in the cerebellar cortex, suggesting an exacerbation of the MS. However, magnetic resonance imaging findings the next day showed cerebral venous sinus thrombosis. His laboratory findings showed low antithrombin activity. Genetic analysis revealed a single-base substitution (C>T) at the codon 359 (Arg to STOP) in the 5th exon portion of the antithrombin gene, heterozygote. In the literature review, 17 cases of multiple sclerosis associated with cerebral venous sinus thrombosis, which occurred after the lumbar puncture and the treatment with high-dose methylpredonisolone in 11 of these cases. In our case, antithrombin deficiency, hyperhomocystinemia, infection, and lumbar puncture were suggested as the risk factors.

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.

Seizures after intracerebral hemorrhage; risk factor, recurrence, efficacy of antiepileptic drug.

OBJECTIVE: This study aimed to determine the risk factors for recurrent post stroke seizure (PSS) and the efficacy of anti-epileptic drugs (AED) in patients having intracerebral hemorrhage (ICH) with initial seizure. METHODS/SUBJECTS: A total of 1920 consecutive patients with ICH from 2004 to 2012 were investigated retrospectively. The relationships among the baseline clinical and radiological data, administration of AED, and incidence of initial and recurrent PSS were evaluated using multiple logistic regression analysis. RESULTS: Seizures occurred in 127 (6.6%) of the 1920 patients, displaying statistically significant relationships with cortical involvement of a cerebral lesion (P<0.001), non-hypertensive ICH (P<0.001), younger age (P<0.001), and severe neurological deficits (P<0.001). Early (4.3%) and late seizure (2.3%) had no significant relationship with the development of recurrent PSS. Larger volume of hematoma was the only independent factor associated with recurrence of PSS (OR 1.03; 95% CI 1.00-1.05; P=0.027). A Kaplan Meier survival analysis revealed that AED treatment had a poor association with recurrence of PSS (P=0.750). CONCLUSIONS: Larger volume of hematoma was predictive of recurrence of PSS. AED therapy had poor association with preventing the recurrence of PSS.

[Riluzole-induced interstitial pneumonia in a case with amyotrophic lateral sclerosis].

A 74-year-old woman was clinically diagnosed with possible amyotrophic lateral sclerosis (ALS) and was administered 100 mg/day of riluzole. After 2 months, she developed dyspnea and experienced gradual difficulty walking. Chest computed tomography revealed ground-glass opacity and consolidation in the lower lobes of both the lungs, thereby suggesting a diagnosis of interstitial pneumonia. Because the condition was suspected to be drug-induced, riluzole administration was discontinued and steroid (methylprednisolone) pulse therapy (1,000 mg/day, 3 days) was started. Her symptoms and radiological findings improved immediately. At 16 months later, she wanted to take riluzole again. She had the similar interstitial pneumonia on the 4(th) day of the re-administration. Drug (riluzole)-induced lymphocyte stimulation tests (DLST) were negative two times. The symptoms of interstitial pneumonia, a rare adverse effect of riluzole, are very similar to worsening symptoms of ALS; therefore, patients with ALS receiving riluzole therapy should be carefully monitored.