Hiroyuki Takayoshi

Validation of a new mass screening tool for cognitive impairment: Cognitive Assessment for Dementia, iPad version

Background We have developed a new screening test for dementia that runs on an iPad and can be used for mass screening, known as the Cognitive Assessment for Dementia, iPad version (CADi). The CADi consists of items involving immediate recognition memory for three words, semantic memory, categorization of six objects, subtraction, backward repetition of digits, cube rotation, pyramid rotation, trail making A, trail making B, and delayed recognition memory for three words. The present study examined the reliability and validity of the CADi. Methods CADi evaluations were conducted for patients with dementia, healthy subjects selected from a brain checkup system, and community-dwelling elderly people participating in health checkups. Results CADi scores were lower for dementia patients than for healthy elderly individuals and correlated significantly with Mini-Mental State Examination scores. Cronbach’s alpha values for the CADi were acceptable (over 0.7), and test–retest reliability was confirmed via a significant correlation between scores separated by a one-year interval. Conclusion These results suggest that the CADi is a useful tool for mass screening of dementia in Japanese populations.

Distinctive Patterns of Three-Dimensional Arterial Spin-Labeled Perfusion Magnetic Resonance Imaging in Subtypes of Acute Ischemic Stroke

BACKGROUND Ischemic penumbra in acute ischemic stroke (AIS) can be evaluated using arterial spin-labeled (ASL) perfusion magnetic resonance imaging (MRI). We used three-dimensional ASL-MRI to examine patients with different stroke subtypes and the clinical utility of the method within 24 hours of AIS onset. SUBJECTS AND METHODS The 55 male and 48 female patients (mean age, 79.0 years) underwent diffusion-weighted imaging (DWI), fluid-attenuated inversion recovery imaging, magnetic resonance angiography, and pulsed continuous ASL perfusion imaging to determine stroke subtype, hypoperfused ASL area, and neurological deficit severity (National Institutes of Health Stroke Scale). Arterial transit artifacts, indicative of occlusive regions or collateral flow, and other stroke indices were compared. RESULTS ASL hypoperfusion was detected in 3 of 9 patients with transient ischemic attack (TIA), 2 of 27 patients with lacunar infarction (LI), 19 of 31 patients with atherothrombotic infarction (AT), and 30 of 36 patients with cardiogenic embolic infarction (CE). ASL abnormalities were significantly less frequent in LI than in AT and CE, and more frequent in CE than in TIA. ASL abnormalities were more prevalent in patients with medium-to-large DWI-assessed lesions than in those with small lesions on DWI. Patients with medium-sized lesions following AT and CE had a high frequency of diffusion-perfusion mismatch. In 4 of the 5 patients who underwent intravenous thrombolytic therapy, ASL hypoperfusion and diffusion-perfusion mismatch were improved and the occluded arteries were recanalized. CONCLUSIONS ASL perfusion studies may provide useful clinical information allowing diffusion-perfusion mismatch detection and treatment selection in AIS patients, depending on stroke subtype.

A Prospective Study of Asymptomatic Intracranial Atherosclerotic Stenosis in Neurologically Normal Volunteers in a Japanese Cohort.

Atherosclerotic stenosis of major intracranial arteries is a leading cause of ischemic stroke in Asia. However, the long-term prognosis of asymptomatic intracranial atherosclerotic stenosis (ICAS) in healthy volunteers has not been fully examined. Here, we conducted a longitudinal study to examine the prognosis of healthy volunteers with asymptomatic ICAS and to determine the risk factors for ICAS, including asymptomatic brain parenchymal lesions. We studied 2,807 healthy Japanese volunteers with no history of stroke (mean age, 62.0 years). They were followed for a mean interval of 64.5 months. The degree of ICAS and the presence of asymptomatic brain lesions were assessed by using magnetic resonance imaging. Asymptomatic ICAS was detected in 166 volunteers (5.9%) at the initial examination. Moderate and mild stenoses were observed in 1.5 and 4.4% of patients, respectively. Significant risk factors for ICAS were older age and a history of hypertension and/or dyslipidemia. During follow-up, ischemic stroke developed in 32 volunteers. Seven strokes occurred in the ICAS group, whose stroke incidence rate was higher than that in the non-ICAS group (0.78 vs. 0.18% per year). According to a Cox regression analysis, asymptomatic ICAS was an independent risk factor for future ischemic stroke after adjustment for age. Furthermore, after asymptomatic brain lesions were taken into account, ICAS was still a significant risk factor for stroke onset. In conclusion, even mild to moderate asymptomatic ICAS was a significant risk factor for future stroke, independent of asymptomatic brain lesions, in a healthy Japanese population. Mild to moderate ICAS might be a therapeutic target for stroke prevention.

Metabolic syndrome is associated with incidence of deep cerebral microbleeds

Metabolic syndrome (MetS) has been associated with silent brain lesions; however, there are no data on the relationship between MetS and the incidence of cerebral microbleeds (CMBs) in Asian populations. The aim of this study was to evaluate the longitudinal association between MetS and incidence of CMBs in the Japanese population. We performed a prospective cohort study involving 684 Japanese participants (mean age, 61.7 years) with a mean 6.5 ± 3.4 years follow-up. All participants underwent 1.5 T magnetic resonance imaging, and CMBs were classified by their locations. Logistic regression analyses were performed to examine the relationship of MetS and its components with the incidence of CMBs. MetS was observed in 7.5% of the study population. Forty-nine (7.2%) subjects (36 had new deep or infratentorial CMBs, 13 had new strictly lobar CMBs) developed new CMBs during the follow-up period. In multivariable analysis, MetS was significantly associated with the incidence of deep or infratentorial CMBs (odds ratio, 4.03; 95% confidence interval, 1.72–9.41), and the elevated blood pressure component was most robustly associated with the incidence of deep or infratentorial CMBs (odds ratio, 5.16; 95% confidence interval, 2.02–13.2). Increased body mass index was also associated with incidence of deep or infratentorial CMBs (odds ratio, 2.45; 95% confidence interval, 1.06–5.67). The present study showed that MetS predicts incidence of CMBs in the deep brain regions and high blood pressure is the most important among the MetS components.

Analysis of Recurrent Stroke Volume and Prognosis between Warfarin and Four Non–Vitamin K Antagonist Oral Anticoagulants' Administration for Secondary Prevention of Stroke

OBJECTIVE We investigated recurrent stroke volume with nonvalvular atrial fibrillation (NVAF) patients treated with non-vitamin K antagonist oral anticoagulants (NOACs) about clinical backgrounds and number of recurrent stroke. METHODS We administered 4 NOACs, dabigatran, rivaroxaban, apixaban, and edoxaban in 101 postcardioembolic strokes with NVAF. In a retrospective study, we measured recurrent stroke volume with magnetic resonance imaging volumetric software and compared them between 10 vitamin K anticoagulant (VKA: warfarin) cases and 13 NOAC cases under anticoagulant therapy. RESULTS Of 101 cases, 31 were started with a VKA and switched to NOACs after 10 recurrent strokes. Other 70 cases were directly started with NOACs and 13 cases with NOACs as first anticoagulants had recurrent stroke. The frequency of recurrent stroke during anticoagulant therapy is not different between the VKA group and the 3 NOACs group. Recurrent stroke volume is significantly larger in the VKA group (26.4 cm3) than in the NOACs group (1.2 cm3). CONCLUSIONS Secondary prevention with NOACs after stroke might be more beneficial than a VKA by reducing recurrent infarct volume.

Retrospective Analysis of Argatroban in 353 Patients with Acute Noncardioembolic Stroke

BACKGROUND Argatroban is a thrombin inhibitor agent for acute noncardioembolic ischemic stroke in Japan. We studied the prognosis in patients with acute stroke treated by argatroban in comparison with the control group with ozagrel in our hospital. SUBJECTS AND METHODS A total of 513 patients with acute noncardioembolic ischemic stroke were enrolled retrospectively from our hospital database. Of all patients with stroke, 353 were administered with argatroban. The other 160 control patients were administered with ozagrel. The patients were examined as to their stroke types, the neurological severity according to the National Institutes of Health Stroke Scale (NIHSS), and clinical outcomes on discharge were determined according to the modified Rankin Scale (mRS). RESULTS A total of 353 patients with acute noncardioembolic stroke, including 138 with lacunar infarction (LIs) and 215 with atherothrombotic infarction (ATI) showed functional recovery by argatroban, but the effectiveness of argatroban was not superior to ozagrel therapy defined by the control group. A total of 255 patients with ATI who were treated with both argatroban and ozagrel showed improvement by 1 point. We could not find any significant difference between argatroban and ozagrel in the 2 stroke subtypes, LI and ATI. We also found that combination therapy of argatroban and edaravone was not superior to argatroban monotherapy in clinical outcome. CONCLUSIONS Argatroban therapy was not superior to control with ozagrel therapy in acute noncardioembolic ischemic stroke, including LI and ATI, regardless of the use of edaravone.

Do Event-Related Evoked Potentials Reflect Apathy Tendency and Motivation?

Apathy is a mental state of diminished motivation. Although the reward system as the foundation of the motivation in the human brain has been studied extensively with neuroimaging techniques, the electrophysiological correlates of motivation and apathy have not been fully explored. Thus, in 14 healthy volunteers, we examined whether event-related evoked potentials (ERP) obtained during a simple number discrimination task with/without rewards reflected apathy tendency and a reward-dependent tendency, which were assessed separately using the apathy scale and the temperament and character inventory (TCI). Participants were asked to judge the size of a number, and received feedback based on their performance in each trial. The P3 amplitudes related to the feedback stimuli increased only in the reward condition. Furthermore, the P2 amplitudes related to the negative feedback stimuli in the reward condition had a positive correlation with the reward-dependent tendency in TCI, whereas the P3 amplitudes related to the positive feedback stimuli had a negative correlation with the apathy score. Our result suggests that the P2 and P3 ERPs to reward-related feedback stimuli are modulated in a distinctive manner by the motivational reward dependence and apathy tendency, and thus the current paradigm may be useful for investigating the brain activity associated with motivation.

The clinical significance of arterial transit artifact on arterial spin labeling in patients with acute ischemic stroke

Arterial spin labeling (ASL) is a noninvasive magnetic resonance imaging (MRI) technique used to assess brain perfusion quantitatively in humans. Many studies have reported the safety and utility of ASL in acute ischemic stroke (AIS); however, few reports have investigated the clinical significance of arterial transit artifact (ATA) in AIS. In this report, we focus on the utility of ATA in AIS.

Analysis of Recurrent Stroke Volume Between VKA (Vitamin K Antagonist) and Three NOACs (Non-Vitamin K Antagonist Oral Anticoagulants) Under Oral Anticoagulant Therapy

Objective: We investigated recurrent stroke volume with nonvalvular atrial fibrillation (NVAF) patients treated with non-vitamin K antagonist oral anticoagulants (NOACs) about clinical backgrounds and number of recurrent stroke. Methods: We administered three NOACs, dabigatran, rivaroxaban and apixaban in 84 post cardioembolic stroke with NVAF. In retrospective study, we measured recurrent stroke volume with MRI volumetry soft and compared them between 7 vitamin K anticoagulant (VKA: warfarin) cases and 10 NOACs cases under anticoagulant therapy. Results: Of 84 cases, 27 cases were started with VKA and switched to NOACs after 7 recurrent stroke. Other 57 cases were directly started with NOACs and 10 cases with NOACs as first anticoagulants had recurrent stroke. The frequency of recurrent stroke during anticoagulant therapy are not different among VKA group and three NOACs group. Recurrent stroke volume is significantly larger in VKA group (27.4 cm3) than in NOACs group (3.3cm3). Conclusions: Secondary prevention with NOACs after stroke might be more beneficial by reducing recurrent infarct volume than VKA.

[A case of Guillain-Barre syndrome in the oldest].

We herein describe the case of a 90-year-old man. He had been treated for type II diabetes mellitus for over twenty years. One day he noticed weakness in the bilateral upper limbs. The next morning the symptoms extended to the bilateral lower limbs. As a result, he was admitted to Shimane University Hospital. MRI showed mild compression of the cervical spinal cord, but it did not account for his neurological symptoms. Because his quadriplegia progressed, we examined the cerebrospinal fluid with albuminocytologic dissociation. A nerve conduction study showed an axonal neuropathy pattern. We diagnosed Guillain-Barre syndrome and started intravenous immunoglobulin (IVIg) therapy 5 mg/kg on the fifth day after admission. All deep tendon reflexes were absent during the treatment. He was able to get up one week later and could walk by himself two weeks later. Guillain-Barre syndrome is a treatable disease and this disorder should be taken into consideration even if an elderly person presents with quadriplegia.