Dual Antiplatelet Therapy With Cilostazol for Secondary Prevention in Lacunar Stroke: Subanalysis of the CSPS.com Trial.

BACKGROUND: The effectiveness of long-term dual antiplatelet therapy (DAPT) to prevent recurrent strokes in patients with lacunar stroke remains unclarified. Therefore, this study aimed to compare and to elucidate the safety and effectiveness of DAPT and single antiplatelet therapy (SAPT) in preventing recurrence in chronic lacunar stroke. METHODS: CSPS.com (Cilostazol Stroke Prevention Study for Antiplatelet Combination) was a prospective, multicenter, randomized controlled trial. In this prespecified subanalysis, 925 patients (mean age, 69.5 years; 69.4% men) with lacunar stroke were selected from 1884 patients with high-risk noncardioembolic stroke, enrolled in the CSPS.com trial after 8 to 180 days following stroke. Patients were randomly assigned to receive either SAPT or DAPT using cilostazol and were followed for 0.5 to 3.5 years. The primary efficacy outcome was the first recurrence of ischemic stroke. The safety outcomes were severe or life-threatening bleeding. RESULTS: The DAPT group receiving cilostazol and either aspirin or clopidogrel and SAPT group receiving aspirin or clopidogrel alone comprised 464 (50.2%) and 461 (49.8%) patients, respectively. Ischemic stroke occurred in 12 of 464 patients (1.84 per 100 patient-years) in the DAPT group and 31 of 461 patients (4.42 per 100 patient-years) in the SAPT group, during follow-up. After adjusting for multiple potential confounding factors, ischemic stroke risk was significantly lower in the DAPT group than in the SAPT group (hazard ratio, 0.43 [95% CI, 0.22-0.84]). The rate of severe or life-threatening hemorrhage did not differ significantly between the groups (2 patients [0.31 per 100 patient-years] versus 6 patients [0.86 per 100 patient-years] in the DAPT and SAPT groups, respectively; hazard ratio, 0.36 [95% CI, 0.07-1.81]). CONCLUSIONS: In patients with lacunar stroke, DAPT using cilostazol had significant benefits in reducing recurrent ischemic stroke incidence compared with SAPT without increasing the risk of severe or life-threatening bleeding. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000012180.

Dual Antiplatelet Therapy Using Cilostazol With Aspirin or Clopidogrel: Subanalysis of the CSPS.com Trial.

Background and Purpose: Although dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduces the recurrence of ischemic stroke while significantly increasing the bleeding events compared with monotherapy, the CSPS.com trial (Cilostazol Stroke Prevention Study combination) showed that DAPT using cilostazol was more effective without the bleeding risk. In the CSPS.com trial, aspirin or clopidogrel was used as the underlying antiplatelet drug. The effectiveness and safety of each combination were examined and clarified. Methods: In the CSPS.com trial, a multicenter, open-label, randomized controlled study, patients with high-risk, noncardioembolic ischemic stroke 8 to 180 days after onset treated with aspirin or clopidogrel alone at the discretion of the physician in charge were recruited. Patients were randomly assigned to receive either monotherapy or DAPT using cilostazol and followed for 0.5 to 3.5 years. The primary efficacy outcome was first recurrence of ischemic stroke. The safety outcome was severe or life-threatening bleeding. The analysis was based on the underlying antiplatelet agents. Results: A total of 763 patients taking aspirin and 1116 taking clopidogrel were included in the intention-to-treat analysis. Although the clopidogrel group had more risk factors than the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the 2 groups. In the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the DAPT group and the aspirin-monotherapy group. In the clopidogrel group, the primary end point occurred at a rate of 2.31 per 100 patient-years in the DAPT group and 5.19 per 100 patient-years in the clopidogrel-monotherapy group (hazard ratio, 0.447 [95% CI, 0.258­0.774]). Safety outcome did not differ significantly between groups (0.51 per 100 patient-years versus 0.71 per 100 patient-years, respectively; hazard ratio, 0.730 [95% CI, 0.206­2.588]). Conclusions: The combination of cilostazol and clopidogrel significantly reduced the recurrence of ischemic stroke without increasing the bleeding risk in noncardioembolic, high-risk patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000012180.

Inhibitory Effects of P2Y12 Receptor Antagonist on PAR1- and PAR4-AP-Induced Platelet Aggregation in Patients with Stroke or TIA.

OBJECTIVES: The inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-activating peptide (AP)-induced platelet aggregation have not been fully elucidated. The present study aimed to investigate the inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-AP-induced platelet aggregation using platelet-rich plasma (PRP) from individuals including patients with stroke or transient ischemic attack (TIA). MATERIALS AND METHODS: PRP was given to 10 healthy individuals pretreated in vitro with cangrelor, then stimulated with adenosine diphosphate (ADP), PAR4-AP, or PAR1-AP. Moreover, 20 patients were enrolled from 148 consecutive patients with acute ischemic stroke or TIA admitted to our institute between December 2017 and April 2019. PRP obtained from each patient before and >7 days after initiation of clopidogrel was similarly stimulated with these agonists. Platelet aggregation was measured using an automatic coagulation analyzer in all participants. RESULTS: In healthy individuals, ADP- and PAR4-AP-induced platelet aggregations were significantly inhibited depending on the cangrelor concentration in vitro, while PAR1-AP-induced platelet aggregation was slightly inhibited. In patients with stroke or TIA, clopidogrel inhibited ADP-induced platelet aggregation at all concentrations, and significantly inhibited PAR4-AP-induced platelet aggregation at 50 µmol/L of PAR4-AP (p<0.05), especially in 5 patients who showed high reactivity to PAR4-AP. PAR1-AP-induced platelet aggregation was also slightly inhibited. CONCLUSIONS: We showed significant inhibitory effects on PAR4-AP-induced platelet aggregation by clopidogrel in patients with stroke or TIA who had high reactivity to PAR4-AP.

Thrombin-induced platelet aggregation -effect of dabigatran using automated platelet aggregometry.

Dabigatran, a direct oral thrombin inhibitor, has two therapeutic effects: anticoagulation; and antiplatelet activity. In the clinical field, evaluation of the effect of dabigatran on thrombin-induced platelet aggregation is difficult because of fibrin clot formation and platelet aggregation. The aim of this study was to establish a new platelet aggregation method and to investigate the effects of dabigatran on thrombin-induced platelet aggregation. Platelet aggregation with thrombin was performed with automated light transmission aggregometry (CS2400; Sysmex, Kobe, Japan) in 40 healthy subjects. Thrombin-induced platelet aggregation was performed using thrombin and platelet-rich plasma (PRP), and thrombin-induced fibrin polymerization was inhibited by adding the peptide Gly-Pro-Arg-Pro (GPRP). The effect of dabigatran was then evaluated using the above method. Thrombin at < 0.2 U/mL did not induce platelet aggregation in most normal subjects. Median maximum aggregation percent (MA%) (25th-75th percentile) with 0.5 and 1.0 U/mL of thrombin was 87.0% (79.3-90.8%), and 90.2% (86.5-92.2%), respectively. The anti-platelet effects of dabigatran were then evaluated with these concentrations of thrombin. Dabigatran (final concentration, 2.5-1000 nM) inhibited platelet aggregation by 0.2-1.0 U/mL of thrombin in a concentration-dependent manner in vitro. Dabigatran showed potent inhibitory effects against platelet aggregation induced by 0.5 and 1.0 U/mL thrombin with half maximal inhibitory concentrations of 10.5 and 40.4 nM, respectively. A standard for thrombin-induced platelet aggregation was developed using the CS2400 in healthy subjects, and dabigatran was confirmed to inhibit thrombin-induced platelet aggregation in vitro with PRP.

Dashcam-captured moment of right hemispheric stroke.

A bus driver presented with neurological abnormalities following a driving mishap. He was diagnosed cardioembolic stroke. The bus was equipped with a dashboard camera that recorded the moment when the patient suffered the stroke. We reported the first case dashcam-captured images at the first sign of a right hemispheric stroke.

[Time-sparing screening method for mild cognitive impairment and early Alzheimer's disease: Self- and family reports using the TMIG index of competence].

AIM: To verify the clinical utility of instrumental activities of daily life evaluated using the Tokyo Metropolitan Institute of Gerontology index of competence (TMIG-IC) as a screening tool for patients with early-phase cognitive impairment, including mild cognitive impairment (MCI) and early Alzheimer's disease (AD). METHODS: We recruited healthy subjects from our community-based cohort and consecutive subjects with MCI and AD from our clinic. The TMIG-IC was investigated in all participants and their family members. The total and subscale scores were compared among all groups. We then statistically determined the accuracy of the differentiation of MCI and AD. RESULTS: We registered 187 normal controls (NC), 39 participants with MCI, 50 AD patients with functional assessment staging (FAST) 4, and 19 AD patients with ≥5 FAST. The family-report score was significantly lower in MCI patients than in others, followed by AD patients. The total score was able to differentiate MCI and AD with a sensitivity of 85.7% and a specificity of 90.9% (area under the curve [AUC]=0.913). Differentiation of MCI alone had a low accuracy (AUC=0.787). However, the AUC was 0.847 when only the items with inconsistent responses between self and family reports were used as indices. CONCLUSIONS: The TMIG-IC is a useful tool for evaluating the severity of AD, including early AD. These findings suggest that family-report scores can differentiate MCI and AD from cognitive normal aging with a sufficient degree of accuracy. It was also suggested that inconsistencies between self and family reports were higher when differentiating MCI than the self- and family-reports.

High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD): A Randomized Superiority Trial.

BACKGROUND: Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous "more versus less statins" trials. However, no clear evidence for more versus less statins has been established in an Asian population. METHODS: In this prospective, multicenter, randomized, open-label, blinded end point study, 13 054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) <120 mg/dL during a run-in period (pitavastatin 1 mg/d) were randomized in a 1-to-1 fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention. RESULTS: The mean age of the study population was 68 years, and 83% were male. The mean LDL-C level before enrollment was 93 mg/dL with 91% of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/dL than in the low-dose group (P<0.001). With a median follow-up of 3.9 years, high-dose as compared with low-dose pitavastatin significantly reduced the risk of the primary end point (266 patients [4.3%] and 334 patients [5.4%]; hazard ratio, 0.81; 95% confidence interval, 0.69-0.95; P=0.01) and the risk of the secondary composite end point (489 patients [7.9%] and 600 patients [9.7%]; hazard ratio, 0.83; 95% confidence interval, 0.73-0.93; P=0.002). High-dose pitavastatin also significantly reduced the risks of several other secondary end points such as all-cause death, myocardial infarction, and clinically indicated coronary revascularization. The results for the primary and the secondary composite end points were consistent across several prespecified subgroups, including the low (<95 mg/dL) baseline LDL-C subgroup. Serious adverse event rates were low in both groups. CONCLUSIONS: High-dose (4 mg/d) compared with low-dose (1 mg/d) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01042730.

[Study of encoding and storage in memorization among patients with Alzheimer's disease].

AIM: Memorization comprises three stages: encoding, storage, and retrieval. Using neuropsychological tests, we investigated the stage at which encoding and storage are retained in Alzheimer's disease (AD) patients with progressive memory disorder. METHODS: The target patients were an amnestic mild cognitive impairment (MCI) group (21 cases) and FAST 4 (37 cases), 5 (10 cases), and 6 (4 cases) AD groups. The neuropsychological tests performed were the Rivermead behavioral memory test and Wechsler memory scale-revised. These were carried out in the MCI group as well as in each AD stage group. We investigated the delayed recall (free recall and cued recall) based on the disease stage and raw score of the sub-items in delayed recognition. RESULTS: The MCI group had 48% (median 0 point) correct respondents (providing ≥1 correct answer) for free recall, whereas FAST 4 and 5 groups had ≤14% correct respondents. In the verbal paired associates II evaluated in cued recall, the MCI group had 90% correct respondents, and the FAST 4, 5, and 6 groups had rates of 51%, 60%, and 50%, respectively. For the pictures and photos in the delayed recognition tasks, there were no significant differences in the percentage of correct respondents between the MCI group (100%) and the FAST 4 and 5 groups (70%-90%). CONCLUSIONS: Given that retrieval is impossible if encoding and storage are impaired, we inferred that the encoding and retrieval abilities were retained even in moderately advanced AD.

Fingolimod induces BAFF and expands circulating transitional B cells without activating memory B cells and plasma cells in multiple sclerosis.

Patients with multiple sclerosis (MS) who are treated with fingolimod have an increased proportion of transitional B cells in the circulation, but the underlying mechanism is not known. We hypothesized that B cell-activating factor of the tumor necrosis factor family (BAFF) is involved in the process. Compared with healthy controls and untreated MS patients, fingolimod-treated MS patients had significantly higher serum concentrations of BAFF, which positively correlated with the proportions and the absolute numbers of transitional B cells in blood. Despite the elevated concentrations of BAFF in fingolimod-treated MS patients, serum levels of soluble transmembrane activator and calcium-modulating cyclophilin ligand interactor, and B cell maturation antigen were not elevated. Our results show that fingolimod induces BAFF in the circulation and expands transitional B cells, but does not activate memory B cells or plasma cells in MS, which is favorable for the treatment of this disease.

Evaluation of Intraplaque Neovascularization Using Superb Microvascular Imaging and Contrast-Enhanced Ultrasonography.

BACKGROUND: Several studies have shown a linkage between intraplaque neovascularization (IPN) and plaque instability. Although contrast-enhanced ultrasonography (CEUS) may help visualize IPN in the carotid artery, its benefits are limited in Japan, where there is no health insurance coverage for contrast agents in medical imaging. Superb microvascular imaging (SMI), however, enables the depiction of low-velocity blood flow. The current study compares the diagnostic accuracy of SMI and CEUS in the evaluation of IPN. METHODS: The SMI and CEUS video images were transferred to a workstation and then analyzed to determine whether intraplaque blood flow signals were detected with SMI and whether plaques were contrast-enhanced with carotid artery CEUS. The images generated were independently interpreted by 2 radiologic technologists and 1 neurologist. RESULTS: Intraplaque enhancement was observed in 19 patients using CEUS while intraplaque blood flow signals were observed in 12 patients using SMI. A 100% specificity was recorded for SMI (all 12 patients with SMI-detected intraplaque blood flow showed contrast-enhanced plaques), while its sensitivity was 63% (8 of the 15 patients with no SMI-detected intraplaque blood flow showed contrast-enhanced plaques on CEUS). CONCLUSIONS: The results of this study show that patients with SMI-detected blood flow will tend to have plaque enhancement using CEUS. This suggests that SMI, as a simpler, safer, and noninvasive technique, can facilitate the visualization of carotid artery IPN without the use of a contrast agent, as well as in the clinical evaluation of plaque instability.

Differential diagnosis of parkinsonism by a combined use of diffusion kurtosis imaging and quantitative susceptibility mapping.

PURPOSE: We investigated whether diffusion kurtosis imaging (DKI) and quantitative susceptibility mapping (QSM) could detect pathological changes that occur in Parkinson's disease (PD), multiple system atrophy with predominant parkinsonism (MSA-P) or predominant cerebellar ataxia (MSA-C), and progressive supranuclear palsy syndrome (PSPS) and thus be used for differential diagnosis that is often difficult. METHODS: Seventy patients (41 with PD, 6 with MSA-P, 7 with MSA-C, 16 with PSPS) and 20 healthy controls were examined using a 3.0 T MRI scanner. From DKI and QSM data, we automatically obtained mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) values of the midbrain tegmentum (MBT), pontine crossing tract (PCT), and superior/middle cerebellar peduncles (CPs), which were used to calculate diffusion MBT/PCT ratios (dMPRs) and diffusion superior/middle CP ratios (dCPRs), as well as MS (magnetic susceptibility) values of the anterior/posterior putamen (PUa and PUp) and globus pallidus (GP). RESULTS: dMPRs of MK were significantly decreased in PSPS and increased in MSA-C compared with the other groups, while dCPRs of MK showed significant differences only between MSA-C and PD, PSPS, or control. MS values were significantly increased in the PUp of MSA-P and in the PUa and GP of PSPS compared with those in PD. The combined use of MK-dMPR and MS-PUp showed sensitivities of 83-100% and specificities of 81-100% for discriminating among the disease groups, respectively. CONCLUSION: A quantitative assessment using DKI and QSM analyses, particularly MK-dMPR and MS-PUp values, can readily identify patients with parkinsonism.

Evaluation of the Efficacy and Safety of Direct Oral Anticoagulants in Japanese Patients-Analysis of Pharmaceuticals and Medical Devices Agency Data.

BACKGROUND: Two forms of direct oral anticoagulant (DOAC) have recently been introduced: direct thrombin inhibitors (DTI; e.g., dabigatran) and factor Xa inhibitors (FXa; e.g., rivaroxaban and apixaban). Despite the advantages of DOACs over warfarin with regard to cerebrovascular complications, those associated with DOACs have been reported with the increasing use of DOACs. Nevertheless, little is known about real-world comparative efficacy and safety of DOACs. METHODS: Cerebrovascular adverse events collected by the Pharmaceutical and Medical Devices Agency (PMDA) during 2014 were analyzed to describe and compare efficacy and safety among patients prescribed DTI and FXa. RESULTS: Thirty-six cerebrovascular events associated with DTI and 419 events with FXa were reported during 2014. Ratios of hemorrhagic to ischemic events were similar in both DTI (2.2) and FXa (1.9) groups, with hemorrhagic events exceeding ischemic events. Ratios of intracerebral hemorrhage to total hemorrhagic events in patients with FXa (0.84) were significantly higher than those taking DTI (0.48; P < .01), but ratios of subdural (epidural) hemorrhage in FXa (0.14) were significantly lower than in DTI (0.44; P < .01). Among patients developing cerebral infarction, ratios of embolic to total ischemic events among FXa (0.34) and DTI (0.31) were comparable, but no patients taking DTI developed atherothrombotic infarction, compared with patients taking FXa (ratio of atherothrombotic to total ischemic events = 0.15). CONCLUSIONS: The present study indicates that different drug effects on cerebrovascular events may exist between DTI and FXa. DTI may play important roles in reducing and preventing intracerebral hemorrhage and atherothrombotic events.

Characteristics of Anatomy and Function of the Left Atrial Appendage and Their Relationships in Patients with Cardioembolic Stroke: A 3-Dimensional Transesophageal Echocardiography Study.

BACKGROUND: Increasing attention is being paid to the left atrial appendage (LAA) in the context of risk stratification in cardioembolic stroke (CES) and the requirement for meticulous planning of percutaneous closure device implantation. However, detailed systematic assessment of the LAA remains limited. METHODS: This study evaluated the anatomy and function of LAA using 3-dimensional transesophageal echocardiography (3D-TEE) on 194 consecutive patients older than 50 years old hospitalized exclusively for CES. Patients were stratified into 3 groups on the basis of cardiac rhythm: (1) chronic atrial fibrillation (AF), n = 53; (2) paroxysmal AF, n = 26; and (3) no detected AF, n = 115. RESULTS: Significant differences between the groups were observed for anatomical (orifice area [OA], depth, diastolic volume) and functional parameters (ejection fraction [EF], flow velocity [FV]), as measured by 3D-TEE. The anatomical parameters were consistently the greatest, and functional parameters were the poorest, in the group with chronic AF. There were significant inverse correlations between them (r = -.33, P = .0003 for depth and EF; r = -.27, P = .0020 for depth and FV; r = -.22, P = .016 for OA and EF; and r = -.38, P < .0001 for OA and FV). CONCLUSIONS: LAA morphology and function were strongly affected by cardiac rhythm disturbances. Patients with chronic AF had the greatest LAA dimensions, areas, and volumes as well as the lowest LAA functions. An inverse correlation was observed between LAA size and function.

T1-Weighted Magnetic Resonance Carotid Plaque Imaging: a Comparison between Conventional and Fast Spin-Echo Techniques.

BACKGROUND: Magnetic resonance imaging is widely used to evaluate the intraplaque components of the cervical carotid artery. The non-gated T1-weighted spin-echo (SE) technique has been reported to have an excellent ability for discriminating stable and unstable plaques. However, the diagnostic performance of various SE-based techniques remains unclear. Hence, we compared plaque signals obtained by 3 kinds of SE-based methods with histological findings. METHODS: We prospectively examined 40 patients who underwent carotid endarterectomy by using 1.5-T scanners and obtained 2-dimensional (2D) conventional spin-echo (CSE), 2D fast spin-echo (FSE), and 3-dimensional (3D)-FSE images with identical repetition times. We calculated contrast ratios (CRs) of the plaques against adjacent muscles and compared these values with the pathological classification of the specimens. RESULTS: The CRs of type VII-VIII (calcific/fibrous), IV-V (lipid-rich/necrotic), and VI (complex/hemorrhagic) plaques were significantly different between all the methods (P <.001) and were discriminated from each other at sensitivities of 83%-100% and specificities of 94%-100%. The CRs of type IV-V plaques significantly differed between the methods (low to high, 2D-FSE, 2D-CSE, and 3D-FSE; P <.05); those of the type VI plaques were significantly lower with the 2D-FSE method than with the other methods (P <.01). CONCLUSIONS: The SE-based T1-weighted images can readily discriminate plaque characteristics with high sensitivities and specificities, although the signal intensity of unstable plaques was significantly high on the 3D-FSE images and significantly low on the 2D-FSE images.

Comparison of Three-Dimensional T1-Weighted Magnetic Resonance and Contrast-Enhanced Ultrasound Plaque Images for Severe Stenosis of the Cervical Carotid Artery.

BACKGROUND AND PURPOSE: Magnetic resonance (MR) and contrast-enhanced ultrasound assess characteristics and neovascularization, respectively, of the carotid plaque. The purpose of the present study was to clarify how findings of contrast-enhanced ultrasound plaque imaging are related to those of 3-dimensional (3D) fast spin echo (FSE) T1-weighted MR plaque imaging (WI) in severe stenosis (≥70%) of the cervical carotid artery. METHODS: Fifty-three patients underwent 3D FSE T1-WI and contrast-enhanced ultrasound. For each patient, the averaged contrast ratio on MR (CRMR) was calculated by dividing the averaged internal carotid artery plaque signal intensity by the sternocleidomastoid muscle signal intensity; maximally enhanced intensities on the intraplaque and lumen time-intensity curves were obtained from contrast-enhanced ultrasound data, and the ratio of the maximal intensity of the intraplaque curve to that of the lumen curve was calculated and defined as contrast effect (CEUS). RESULTS: A linear correlation (r = .702; P <.0001) was observed between CRMR and CEUS. Receiver operating characteristic curve analyses to evaluate the ability of the CEUS to differentiate each category of CRMR from the other 2 categories showed that the sensitivity was significantly lower for category II (1.30 ≤ CRMR ≤ 1.60) than for category I (CRMR < 1.30) or III (1.60 < CRMR). The CEUS was lower in plaques with higher CRMR than in those with lower CRMR in a subgroup of category III (P = .0196). CONCLUSION: Findings of contrast-enhanced ultrasound plaque imaging are related to those of 3D FSE T1-WI MR plaque imaging according to the life history of arterial plaque and its neovascularization.

Conceptual definition in the metamorphosing Parkinson's disease.

Two hundred years ago, James Parkinson wrote 'An Essay on the Shaking Palsy'. The discovery of Lewy bodies in the substantia nigra and dopamine deficiency in the nigro- striatal dopaminergic system have confirmed the disease concept of Parkinson's disease. Dopamine replacement therapy dramatically improves the clinical prognosis. However, variable nonmotor symptoms have been noticed by many clinical researches, which can deteriorate the quality of life. Visual hallucination, fall and dementia can prescribe the late stage prognosis. In addition, part of nonmotor symptoms can develop before motor symptoms appear. Nowadays, the prodromal stage of Parkinson's disease may be detected using with the research criteria. The disease concept of Parkinson's disease is still metamorphosing under the storage of the novel evidences.

Detection of changes in the periaqueductal gray matter of patients with episodic migraine using quantitative diffusion kurtosis imaging: preliminary findings.

INTRODUCTION: The periaqueductal gray matter (PAG) is considered to play an important role in generating migraine, but findings from imaging studies remain unclear. Therefore, we investigated whether diffusion kurtosis imaging (DKI) can detect changes in the PAG of migraine patients. METHODS: We obtained source images for DKI from 20 patients with episodic migraine and 20 healthy controls using a 3 T magnetic resonance imaging scanner. Mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) maps were generated, and the values of the PAG and other deep gray and white matter structures were automatically measured using an atlas-based region-of-interest analysis. The metrics of these structures were compared between the patients and controls. RESULTS: The MK and MD values of the PAG were significantly increased in the migraine patients compared with the controls (p < 0.05). The FA values were not significantly different. There were no significant differences in the metrics of the other structures between the patients and controls. The MK values of the PAG were significantly positively correlated with both age and the untreated period in the patient group under univariate analysis (r = 0.53 and 0.56, respectively; p < 0.05) but not multivariate analysis. CONCLUSIONS: DKI detected significant increases in the MK and MD values of the PAG in patients with migraine, which suggests that structural changes in the PAG are associated with the pathophysiological mechanisms of migraine.

Preoperative 3D FSE T1-Weighted MR Plaque Imaging for Severely Stenotic Cervical ICA: Accuracy of Predicting Emboli during Carotid Endarterectomy.

The aim of the present study was to determine whether preoperative three-dimensional (3D) fast spin-echo (FSE) T1-weighted magnetic resonance (MR) plaque imaging for severely stenotic cervical carotid arteries could accurately predict the development of artery-to-artery emboli during exposure of the carotid arteries in carotid endarterectomy (CEA). Seventy-five patients underwent preoperative MR plaque imaging and CEA under transcranial Doppler ultrasonography of the ipsilateral middle cerebral artery. On reformatted axial MR image slices showing the maximum plaque occupation rate (POR) and maximum plaque intensity for each patient, the contrast ratio (CR) was calculated by dividing the internal carotid artery plaque signal intensity by the sternocleidomastoid muscle signal intensity. For all patients, the area under the receiver operating characteristic curve (AUC)-used to discriminate between the presence and absence of microembolic signals-was significantly greater for the CR on the axial image with maximum plaque intensity (CRmax intensity) (0.941) than for that with the maximum POR (0.885) (p < 0.05). For 32 patients in whom both the maximum POR and the maximum plaque density were identified, the AUCs for the CR were 1.000. Preoperative 3D FSE T1-weighted MR plaque imaging accurately predicts the development of artery-to-artery emboli during exposure of the carotid arteries in CEA.

Intracranial Plaque Characterization in Patients with Acute Ischemic Stroke Using Pre- and Post-Contrast Three-Dimensional Magnetic Resonance Vessel Wall Imaging.

BACKGROUND: Magnetic resonance vessel wall imaging (VWI) techniques have been developed to assess atherosclerotic plaques in intracranial arteries, which are a cardinal cause of ischemic stroke. However, the clinical roles of plaque-related vulnerability and inflammation remain unclear. Hence, we evaluated plaque characteristics using VWI of the proximal middle cerebral artery (M1) in patients with acute ischemic stroke. METHODS: We prospectively examined 30 consecutive patients with acute noncardioembolic stroke in the M1 territory using pre-/postcontrast T1-weighted (T1W) three-dimensional (3D) VWI with a 3-Tesla scanner. The contrast ratio (CR) and contrast enhancement of the plaques were measured bilaterally at M1. RESULTS: Plaques were identified in the bilateral M1s of all patients, and no substantial stenosis existed. The M1 plaque CRs ipsilateral to the infarct (46.7%-67.9%) were significantly higher than the plaque CRs on the contralateral side (34.3%-69.4%), particularly in patients with lacunar infarcts (P <.01). In contrast, the occurrence of plaque enhancement was not different between the ipsilateral (20.0%) and contralateral (16.7%) sides. Further, the CRs in the nonlacunar group were significantly higher than the CRs in the lacunar group (P <.05), whereas enhanced plaques tended to be more frequent in the nonlacunar group, but this difference was not significant (P = .09). CONCLUSIONS: T1W 3D-VWI revealed that the signal intensity of M1 plaques was significantly higher in the affected side and in nonlacunar-type infarcts of patients with acute stroke, suggesting that unstable plaques in the M1 can cause stroke events presumably due to atherothrombotic mechanisms.

Early pathological alterations of lower lumbar cords detected by ultrahigh-field MRI in a mouse multiple sclerosis model.

Magnetic resonance imaging (MRI) is widely employed for the diagnosis of multiple sclerosis (MS). However, sometimes, the lesions found by MRI do not correlate with the neurological impairments observed in MS patients. We recently showed autoreactive T cells accumulate in the fifth lumbar cord (L5) to pass the blood-brain barrier and cause inflammation in the central nervous system of experimental autoimmune encephalomyelitis (EAE) mice, an MS model. We here investigated this early event using ultrahigh-field MRI. T2-weighted image signals, which conform to the water content, increased in L4 and L5 during the development of EAE. At the same time, the sizes of L4 and L5 changed. Moreover, angiographic images of MRI showed branch positions of the blood vessels in the lower lumbar cords were significantly altered. Interestingly, EAE mice showed occluded and thickened vessels, particularly during the peak phase, followed by reperfusion in the remission phase. Additionally, demyelination regions of some MS patients had increased lactic acid content, suggesting the presence of ischemic events. These results suggest that inflammation-mediated alterations in the lower lumbar cord change the homeostasis of the spinal cord and demonstrate that ultrahigh-field MRI enables the detection of previously invisible pathological alterations in EAE.