Changes in Whole-Blood microRNA Profiles during the Onset and Treatment Process of Cerebral Infarction: A Human Study.

Circulating miRNA species are promising symptom markers for various diseases, including cardiovascular disease. However, studies regarding their role in the treatment process are limited, especially concerning cerebral infarction. This study aimed to extract miRNA markers to investigate whether they reflect both onset and treatment process of cerebral infarction. A total of 22 patients (P-group) and 22 control subjects (C-group) were examined for their whole-blood miRNA profiles using DNA GeneChip™ miRNA 4.0 Array, with six patients examined after treatment (T-group). A total of 64 miRNAs were found to be differentially expressed between the C- and P-groups. Out of 64 miRNAs, the expression levels of two miRNAs correlated with hypertension. A total of 155 miRNAs were differentially expressed between the P- and T-groups. Five common miRNAs were found among the 64 and 155 miRNAs identified. Importantly, these common miRNAs were inversely regulated in each comparison (e.g., C < P > T), including miR-505-5p, which was previously reported to be upregulated in aortic stenosis patients. Our previous study using rat cerebral infarction models detected the downregulation of an apoptosis repressor, WDR26, which was repressed by one of the five miRNAs. Our results provide novel information regarding the miRNA-based diagnosis of cerebral infarction in humans. In particular, the five common miRNAs could be useful makers for the onset and the treatment process. Trial registration: This study was registered in the UMIN Clinical Trials Registry (UMIN000038321).

Early Cognitive Impairment after Minor Stroke: Associated Factors and Functional Outcome.

OBJECTIVES: Evaluation of cognitive status is not performed routinely in the acute stroke setting. This study aimed to evaluate the frequency of early cognitive impairment in patients with minor ischemic stroke, analyze the factors associated with early cognitive impairment, and assess functional outcomes. METHODS: In this prospective study, 112 consecutive patients with acute minor ischemic stroke were enrolled. Neuroimages were assessed for semiquantitative evaluation of brain atrophy and small vessel disease (SVD) markers. Cognitive performance was measured within 5 days of onset using Montreal Cognitive Assessment (MoCA) scores. Functional outcome analyses were adjusted for demographic variables, premorbid cognitive status, education level, vascular risk factors, neuroimaging characteristics, stroke severity, and MoCA scores. RESULTS: The median MoCA score was 22, and 63% of patients had cognitive impairment. Factors independently associated with cognitive impairment were education (odds ratios [OR], .79; confidence intervals [CI], .63-.99), smoking (OR, .26; 95%CI, .073-.89), and temporal horn atrophy (OR, 4.73; 95% CI, 1.66-13.49). Factors independently associated with poor functional outcome were total MoCA score (OR, .78; 95%CI, .62-.95) and the sum of 4 MoCA subscores (visuospatial/executive, attention, language, and orientation; OR, .72; 95%CI, .53-.92). The cutoff value of the sum of 4 MoCA subscores for predicting poor outcome was 13 points with 76.5% sensitivity and 81.1% specificity. CONCLUSIONS: Early cognitive impairment was common after minor ischemic stroke and was associated with preexisting temporal horn atrophy but not SVD markers. The sum of 4 MoCA subscores was useful in predicting the functional outcome.

Early Cognitive Assessment Following Acute Stroke: Feasibility and Comparison between Mini-Mental State Examination and Montreal Cognitive Assessment.

OBJECTIVES: Cognitive assessment is not performed routinely in the acute stroke setting. We investigated factors associated with cognitive impairment and the differences between the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores in patients with acute stroke. METHODS: In this prospective study, 881 consecutive patients (median age, 73 years) with acute stroke were enrolled. Clinical characteristics, such as education, vascular risk factors, premorbid cognitive status using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), and stroke severity, were assessed. Cognitive performance was measured using MMSE and MoCA within 5 days of stroke onset. RESULTS: Both MMSE and MoCA were feasible in 621 (70.5%) patients. Factors independently associated with nonfeasibility were age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.02-1.08), IQCODE score (OR: 1.02; 95%CI: 1.00-1.04), and National Institutes of Health Stroke Scale (NIHSS) score (OR, 1.16; 95%CI, 1.12-1.20). Impaired MoCA (with a cut-off <26/30) performance was observed in 544 of 621 (87.6%) patients. Factors independently associated with cognitive impairment were age (OR: 1.06; 95%CI: 1.03-1.10) and NIHSS score (OR: 1.34; 95%CI: 1.14-1.57). Eighty percent of patients with normal MMSE scores had an impaired MoCA score (MMSE-MoCA mismatch). The differences were highest in the visuospatial (94.8% versus 65.3%; P < .0001), recall (76.6% versus 35.6%; P < .0001), abstraction (82.5% versus 49.8%; P < .0001), and language (72.3% versus 65.9%; P < .0001) domains between the normal MMSE and MoCA group and MMSE-MoCA mismatch group. CONCLUSIONS: The MoCA can be particularly useful in patients with cognitive deficits undetectable on the MMSE in the acute stroke phase.

Safety of Anticoagulant Therapy Including Direct Oral Anticoagulants in Patients With Acute Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Because the efficacy and safety of anticoagulant therapy in patients with acute intracerebral hemorrhage (ICH) are not fully known, present study aimed to elucidate the current status and the safety of anticoagulant therapy, mainly direct oral anticoagulants (DOACs), for acute ICH and anticoagulant-indicated patients. Methods and Results: From September 2014 through March 2017, consecutive patients with acute (<7 days from onset), spontaneous ICH were retrospectively enrolled from a prospective registry. Whether to start anticoagulation was at the attending physicians' discretion, and thromboembolic or hemorrhagic events during hospitalization were analyzed. A total of 236 patients (80 women [34%]; median age 69 [interquartile range 61-79] years; National Institutes of Health stroke scale score 7 [3-16]) were enrolled. Of them, 47 patients (20%) had an indication for anticoagulant therapy (33 had atrial fibrillation, 14 developed deep vein thrombosis), and 41 of 47 patients (87%) were actually treated with anticoagulant therapy (DOACs were used in 34 patients) after a median of 7 days from ICH onset. There was neither hematoma expansion nor excessive hemorrhagic complications during hospitalization after starting anticoagulant therapy. CONCLUSIONS: Anticoagulant therapy was conducted for approximately 90% of anticoagulation-indicated patients after a median of 7 days from ICH onset. The predominant anticoagulant medications were DOACs. Anticoagulant therapy started from the acute phase of ICH should be safe.

Characteristics of Acute Spontaneous Intracerebral Hemorrhage in Patients Receiving Oral Anticoagulants.

OBJECTIVE: We investigated the precise clinical and radiologic characteristics of intracerebral hemorrhage associated with direct oral anticoagulant use. METHODS: Patients with acute spontaneous intracerebral hemorrhage admitted to our department from September 2014 to November 2017 were retrospectively analyzed. Clinical and neuroradiological characteristics of patients with direct oral anticoagulant-related intracerebral hemorrhage, and effects of prior treatment on the severity at admission and on outcome at discharge were assessed. RESULTS: Of the 301 enrolled patients (103 women; median age 68 years), 261 received no oral anticoagulants (86.8%), 20 received warfarin (6.6%), and 20 received direct oral anticoagulants (DOACs) (6.6%). Median initial National Institutes of Health Stroke Scale scores differed significantly among the groups (P = .0283). Systolic blood pressure (P = .0031) and estimated glomerular filtration rate (P = .0019) were significantly lower in the oral anticoagulant-related intracerebral hemorrhage group than in other groups. Total small vessel disease scores were significantly higher in the oral anticoagulant-related intracerebral hemorrhage group than in the warfarin group (P = .0413). Multivariate analysis revealed that prior oral anticoagulant treatment (odds ratio: 0.21, 95% confidence interval: 0.05-0.96, P = .0445) was independently negatively associated with moderate-to-severe neurological severity (stroke scale score ≥10) after adjusting for intracerebral hemorrhage location and various risk factors. There were significant differences in hematoma volume in the basal ganglia (P = .0366). CONCLUSIONS: DOAC-related intracerebral hemorrhage may occur particularly in patients with a high risk of bleeding; however, they had a milder initial neurological severity than those with warfarin-related intracerebral hemorrhage, possibly due to relatively smaller hematoma volume, especially in the basal ganglia.

Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants: The PASTA Registry - Study Design and Characteristics.

OBJECTIVES: The management of atrial fibrillation and deep venous thrombosis has evolved with the development of direct oral anticoagulants (DOAC), and oral anticoagulant (OAC) might influence the development or clinical course in both ischemic and hemorrhagic stroke. However, detailed data on the differences between the effects of the prior prescription of warfarin and DOAC on the clinical characteristics, neuroradiologic findings, and outcome of stroke are limited. DESIGN: The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke (ischemic stroke, transient ischemic attack, and intracerebral hemorrhage) patients receiving OAC in Japan. This study is designed to collect data on clinical background characteristics, drug adherence, drug dosage, neurological severity at admission and discharge, infarct or hematoma size, acute therapy including recanalization therapy or reverse drug therapy, and timing of OAC re-initiation. Patient enrollment started in April 2016 and the target patient number is 1000 patients. CONCLUSIONS: The PASTA prospective registry should identify the status of stroke patients taking OAC in the current clinical practice in Japan.

Anticoagulants, Reperfusion Therapy, and Outcomes in Ischemic Stroke Patients With Non-Valvular Atrial Fibrillation　- A Single-Center, 6-Year Experience of 546 Consecutive Patients.

BACKGROUND: This study investigated changes in anticoagulant use, treatment, and functional outcomes in acute ischemic stroke (AIS) patients with non-valvular atrial fibrillation (NVAF) over a 6-year period. Methods and Results: Patients with AIS and NVAF admitted to our department from April 2011 to March 2017 were analyzed retrospectively. Patients were divided into 3 groups based on the time of the initial visit (Periods 1-3, corresponding to April 2011-March 2013, April 2013-March 2015, and April 2015-March 2017, respectively). Associations between prescribed medication prior to event and stroke severity, reperfusion therapy, and outcomes were assessed. There was no significant change in the rate of insufficient warfarin and inappropriately lowered doses of direct oral anticoagulant (DOAC) treatment over time. The number of patients receiving prior DOAC treatment increased, but neurological severity on admission was milder than in the other 2 groups. The rate of reperfusion therapy increased from 19.9% (Period 1) to 42.7% (Period 3) for moderate-to-severe stroke patients. Multivariate logistic regression analysis revealed that reperfusion therapy was independently positively associated with good functional outcomes, but negatively associated with mortality (odds ratios [95% confidence intervals] 7.14 [3.34-15.29] and 0.13 [0.008-0.69], respectively). CONCLUSIONS: Inappropriate anticoagulant use for stroke patients with NVAF did not decrease over time. An increase in reperfusion therapy was a strong factor in improved functional outcomes and mortality.

Insufficient Warfarin Therapy Is Associated With Higher Severity of Stroke Than No Anticoagulation in Patients With Atrial Fibrillation and Acute Anterior-Circulation Stroke.

BACKGROUND: Insufficient anticoagulant intensity on admission is common in stroke patients with atrial fibrillation (AF) on vitamin K antagonist (VKA) therapy. Nevertheless, the effects of VKA under-treatment on stroke severity or arterial occlusion are not well known. The aim of the present study was to investigate the relationship between insufficient VKA therapy and stroke severity, or the site of arterial occlusion in patients with acute ischemic stroke (AIS) and AF.Methods and Results:From March 2011 through July 2016, 446 consecutive patients with AF and AIS were recruited. Of the 446 patients, 364 (167 women; median age, 79 years; IQR, 71-86 years) with anterior-circulation stroke were assessed to investigate the effects of insufficient VKA. Of these, 281 were on no anticoagulant, 53 were undertreated with a VKA, and 30 were sufficiently treated with VKA on admission (PT-INR ≥2.0 for patients <70 years and PT-INR ≥1.6 for ≥70 years old). On multivariate analysis, insufficient VKA was independently associated with severe stroke (i.e., initial NIHSS score ≥10; OR, 2.70, P=0.022) and higher prevalence of proximal artery occlusion (OR, 1.91; P=0.039) compared with no anticoagulant therapy. CONCLUSIONS: Insufficient VKA therapy on admission was associated with higher severity of stroke and higher prevalence of proximal artery occlusion in patients with AF and acute anterior-circulation stroke compared with no anticoagulant medication.

In Hyperacute Recanalization Therapy, Early Hospital Arrival Improves Outcome in Patients with Large Artery Occlusion.

BACKGROUND: It is unknown whether the effect of onset---to-door (OTD) time on clinical outcomes differs between -patients with and without large artery occlusion (LAO) who undergo hyperacute recanalization therapy. METHODS: Hyperacute recanalization therapy includes intravenous thrombolysis tissue-plasminogen activator (tPA), and endovascular therapy (EVT). Favorable clinical outcome was defined as modified Rankin Scale of ≤2 at discharge. RESULTS: Among 164 patients, 117 (71%) patients received tPA, 86 (52%) received EVT, and 39 (24%) received tPA and EVT. One hundred and fifteen patients (70%) were classified into the LAO group and 49 (30%) into the non-LAO group. In the total cohort, multivariate regression analysis showed OTD time (OR 0.809 [95% CI 0.693-0.944], p = 0.007) was an independent factor related to the favorable outcome. Similarly, among patients with LAO, OTD was an independent negative factor for the favorable outcome (0.779 [0.646-0.940], p = 0.009). On the contrary, OTD was not associated with the favorable outcome (1.5 [0.7-2.5] vs. 1.7 [1.1-3.2], p = 0.155) in patients without LAO. This was confirmed with multivariate regression analysis, which did not show OTD to be an independent factor for the favorable outcome (0.900 [0.656-1.236], p = 0.516). CONCLUSION: The effect of early hospital arrival on clinical outcome differed between patients with and without LAO.

Acute Poststroke Depression Is Associated with Thalamic Lesions and Clinical Outcomes: A Case-Control Study.

BACKGROUND: We investigated the role of acute-phase stroke lesions and patient characteristics in poststroke depression (PSD) and its effect on the clinical outcome. PATIENTS AND METHODS: Five and 30 days after admission, 175 patients self-reported their depressive symptoms on the Patient Health Questionnaire-9. We compared the clinical characteristics and outcomes in patients with (n = 41) and without PSD (n = 134). Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS); the modified Rankin Scale (mRS) was used to determine the functional outcome. RESULTS: There was no significant difference between patients with and without PSD in the age, gender ratio, lesion side, and the history of hypertension, diabetes mellitus, alcohol and tobacco use, and previous stroke. Thalamic lesions were significantly associated with PSD (P = .03), although there was no significant difference in both the NIHSS score and the final mRS score of patients with thalamic lesions. Backward stepwise logistic regression analysis showed that a higher NIHSS score and thalamic lesions were independent predictors of PSD. Total hospitalization was significantly longer in patients with PSD. At the time of admission, the NIHSS score was significantly higher in patients who developed moderate to severe PSD than in those with mild PSD or without PSD. CONCLUSIONS: PSD in the acute phase was associated with thalamic lesions and severe stroke. Hospitalization was significantly longer in patients with PSD and their functional disability was more severe, suggesting that PSD played a role in the unsatisfactory results of poststroke rehabilitation.

Low Free Triiodothyronine Predicts 3-Month Poor Outcome After Acute Stroke.

BACKGROUND AND PURPOSE: The association between thyroid hormone levels and long-term clinical outcome in patients with acute stroke has not yet been thoroughly studied. The purpose of the present study was to test the hypothesis that thyroid hormone levels are associated with 3-month functional outcome and mortality after acute stroke. METHODS: We retrospectively analyzed 702 consecutive patients with acute stroke (251 women; median age, 73 years) who were admitted to our department. General blood tests, including thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were performed on admission. Neurological severity was evaluated using National Institutes of Health Stroke Scale (NIHSS) scores on admission and modified Rankin Scale (mRS) scores at 3 months after stroke onset. Poor outcome was defined as an mRS score of 3-5 or death. The impact of thyroid function on 3-month outcome was evaluated using multiple logistic regression analysis. RESULTS: Poor functional outcome was observed in 295 patients (42.0%). Age (P < .0001), female sex (P < .0001), admission NIHSS score (P < .0001), smoking (P = .0026), arterial fibrillation (P = .0002), preadmission mRS (P < .0001), estimated glomerular filtration rate (P = .0307), and ischemic heart disease (P = .0285) were significantly associated with poor functional outcome, but no relationship between FT4, TSH, and poor functional outcome was found. A multivariate logistic regression analysis showed that low FT3 values (<2.00 pg/mL) were independently associated with poor functional outcome (odds ratio [OR], 3.16; 95% confidence interval [CI], 1.60-6.24) and mortality (OR, 2.55; 95% CI, 1.33-4.91) at 3 months after stroke onset. CONCLUSIONS: Our data suggest that a low FT3 value upon admission is associated with a poor 3-month functional outcome and mortality in patients with acute stroke.

Low Free Triiodothyronine at Admission Predicts Poststroke Infection.

BACKGROUND: Poststroke infection (PSI) is common and is usually associated with a severe prognosis. We investigated the association between PSI and thyroid hormones, which are critical to immune regulation, in patients with acute stroke. METHODS: We retrospectively enrolled 520 consecutive patients with acute ischemic stroke (326 men; age, 71.9 ± 13.2 years) admitted to our department between September 2014 and June 2016. The impact of serum thyroid hormone levels measured at admission (thyroid-stimulating hormone [TSH], free triiodothyronine [FT3], and free thyroxine [FT4]) on the PSI was evaluated using multivariate logistic regression analysis. RESULTS: We diagnosed 107 patients (20.6%; pneumonia, 65; urinary tract infection, 19; others, 23) with PSIs. While age (P <.001), body mass index (P = .0012), preadmission modified Rankin scale score (P = .0001), National Institutes of Health Stroke Scale score on admission (P <.001), admission FT3 level (P <.001), atrial fibrillation (P <.001), and ischemic heart disease (P = .0451) were significantly associated with PSI, we found no relationship among TSH levels, FT4 levels, and PSI occurrence. After multivariate adjustment, patients with PSIs were more frequently in the Q1 quartile (≤2.25 pg/mL) than in the Q2 (2.26-2.55 pg/mL; P = .0251), Q3 (2.56-2.89 pg/mL; P = .0007), or Q4 (≥2.90 pg/mL; P = .0010) quartiles of FT3 levels. Moreover, low FT3 levels (<2.29 pg/mL) were independently associated with PSI occurrence (P = .0013). CONCLUSIONS: Low FT3 levels at admission are independently associated with PSI occurrence.

Adenosine A1 receptors measured with 11 C-MPDX PET in early Parkinson's disease.

Adenosine A1 receptors (A1 Rs) interact negatively with dopamine D1 receptors (D1 Rs) in neurons of the basal ganglia's direct pathway, while adenosine A2A receptors (A2A Rs) negatively interact with dopamine D2 receptors (D2 Rs) in indirect-pathway neurons. The aim of this study was to investigate the cerebral density of A1 Rs in Parkinson's disease (PD) in its early stages, using PET scans with the radioligand 8-dicyclopropylmethyl-1-11 C-methyl-3-propylxanthine (11 C-MPDX). We studied 10 drug-naïve patients with early PD. Each patient was also examined for dopamine transporters (DATs) and D2 Rs by PET using 11 C-2-ß-carbomethoxy-3-ß-(4-fluorophenyl)-tropane (11 C-CFT) and 11 C-raclopride (11 C-RAC), respectively. Ten elderly, healthy volunteers were recruited as controls for 11 C-MPDX PET scanning and eight elderly volunteers were recruited as controls for 11 C-CFT and 11 C-RAC PET scanning. The PET scans revealed a decrease in the uptake ratio index (URI) of 11 C-CFT and an increase in the URI of 11 C-RAC in patients. In the temporal lobe, the binding potential for 11 C-MPDX was higher in the patient group than in healthy subjects, but not in the other regions examined, including the striatum. In patients, we observed motor-symptom asymmetry and a relationship between parkinsonism and the striatal density of DATs, but not A1 R density. In the putamen of early PD, asymmetrical down-regulation of A2A Rs is likely a compensatory mechanism in response to a decrease in dopamine. However, our study suggests that A1 Rs are unaltered in the putamen of early PD.

The Prevalence of and Factors Related to Vascular Hyperintensity on T1-Weighted Imaging in Acute Ischemic Stroke.

BACKGROUND: Thrombus visualization in patients with acute ischemic stroke has been detected and reported using various imaging modalities. T1-weighted imaging (T1-WI) can depict thrombi as hyperintense signals within vessels. Moreover, in addition to thrombi, T1-WI hyperintensities in arteries may suggest arterial dissection. However, the frequency of and factors related to the T1-hyperintense vessel sign (T1-HVS) are not fully known. The aim of this study was to clarify the prevalence of and related factors for the T1-HVS in patients with acute ischemic stroke. METHODS: From September 2014 through December 2015, consecutive acute ischemic stroke patients who were admitted to our stroke unit within 7 days from symptom onset were retrospectively recruited from the prospective registry. A T1-HVS was defined as the presence of a hyperintense signal, with intensity higher than surrounding brain, within the vessel lumen. Moreover, T1-HVSs were separated into filled T1-HVSs (hyperintensity fills whole vessel lumen) and non-filled T1-HVSs. The frequency of the T1-HVS and the timing of emersion and the relationship between the presence of the T1-HVS and arterial occlusion were assessed. RESULTS: A total of 399 patients (139 women; median age 73 years; National Institutes of Health Stroke Scale score 3) were enrolled in the present study. Of these, 327 (82%) patients had T1-WI on admission. Two hundred and sixty-seven (67%) subjects had at least one follow-up T1-WI (median 6 days after admission), and 134 (34%) cases had ≥2 follow-up T1-WI examinations. The T1-HVS was observed in 18 patients during admission; therefore, the frequency of the T1-HVS in acute ischemic stroke patients was 4.5% (95% CI 2.5-6.5%). All but one (94%) of the T1-HVSs were first observed on follow-up imaging, and the median number of days from onset to T1-HVS appearance was 9. For patients having initial major artery occlusion and follow-up MRI (n = 95), sensitivity and specificity of the T1-HVS for persistent arterial occlusion on follow-up MR angiography were 22 and 100%, respectively. T1-HVS persisted for a few months and then normalized. Although there were no significant differences between filled and non-filled T1-HVS, more patients with non-filled T1-HVS had arterial dissection (43%) than those with filled T1-HVS (9%, p = 0.245). CONCLUSION: The T1-HVS was observed in 4.5% of acute ischemic stroke patients. T1-HVSs appeared in the subacute phase in arteries with persistent occlusion and remained for a few months.

Peptide Tag-Induced Horseradish Peroxidase-Mediated Preparation of a Streptavidin-Immobilized Redox-Sensitive Hydrogel.

Several methods have recently been reported for the preparation of redox-sensitive hydrogels using enzymatic reactions, which are useful for encapsulating sensitive materials such as proteins and cells. However, most of the reported hydrogels is difficult to add further function efficiently, limiting the application of the redox-sensitive hydrogels. In this study, peptide sequences of HHHHHHC and GGGGY (Y-tag) were genetically fused to the N- and C-termini of streptavidin (C-SA-Y), respectively, and C-SA-Y was mixed with horseradish peroxidase and thiol-functionalized 4-arm polyethylene glycol to yield a redox-sensitive C-SA-Y immobilized hydrogel (C-SA-Y gel). The C-SA-Y immobilized in the hydrogel retained its affinity for biotin, allowing for the incorporation of proteins and small molecules to hydrogel via biotin. C-SA-Y gel was further prepared within a water-in-oil (w/o) emulsion system to yield a nanosized hydrogel, to which any intracellular and cytotoxic agent can be modified, making it a potential drug delivery carrier.

Thrombolysis, Complete Recanalization, Diffusion Reversal, and Luxury Perfusion in Hyperacute Stroke.

A 59-year old man was admitted to our stroke care unit 1.8 hours after onset of cardioembolic stroke. Administration of issue-plasminogen activator achieved complete recanalization, and his lesion on diffusion-weighted imaging (DWI) disappeared and single photon emission computed tomography showed luxury perfusion. DWI reversal and luxury perfusion were sometimes observed in hyperacute stroke patients, especially timely reperfusion was achieved. However, the relationships between DWI reversal and luxury perfusion were not well known. Transient DWI reversal may be associated with luxury perfusion in patients treated with t-PA, via early complete recanalization achieved by thrombolysis.

The potentially protective effect of donepezil in Alzheimer's disease.

BACKGROUND/AIMS: Donepezil is an acetylcholinesterase inhibitor used to treat Alzheimer's disease (AD). In this study, we used a voxel-based specific regional analysis system for AD (VSRAD) to analyze the hippocampal volume and to assess the pharmacologic effects of donepezil as a disease modifier. METHODS: A total of 185 AD patients underwent MRI, 120 (43 men and 77 women, 77.8 ± 7.1 years) without and 65 (29 men and 36 women, 78.4 ± 6.0 years) with donepezil treatment. VSRAD was compared in both groups and against a database of 80 normal subjects. The Z-score was used to assess the degree of hippocampal atrophy. RESULTS: No significant difference between the groups was found for age, sex, or Z-scores, but a significant difference was found for mean Mini-Mental State Examination (MMSE) scores (p = 0.02, Student's t test). Single regression analysis showed no significant association between Z-scores and MMSE scores in the treated group (p = 0.494), but a significant association in the untreated group (p = 0.001) was observed. This implies that the MMSE score becomes lower when the Z-score is higher in the untreated group, whereas there is no significant trend in the treated group. CONCLUSION: Donepezil affects the relationship between hippocampal volume and cognitive function and may therefore have a pharmacologic effect as a disease modifier.

Safety of Antithrombotic Therapy within 24 Hours after Recombinant Tissue-Plasminogen Activator Treatment for Large-Artery Atherosclerosis Stroke: Insights from Emergent PTA/CAS Cases.

BACKGROUND: Antithrombotic therapy (AT) should generally be avoided within 24 hours after recombinant tissue-plasminogen activator (rt-PA) treatment but should be considered in patients with large-artery atherosclerosis (LAA) who undergo concomitant emergent endovascular treatment (EVT). The aim of the present study was to assess the safety of AT within 24 hours after rt-PA treatment in patients with hyperacute ischemic stroke due to LAA who received concomitant EVT. METHODS: From January 2013 through July 2019, consecutive patients with acute ischemic cerebrovascular disease due to LAA who were admitted within 6 hours from symptom onset were recruited. The patients were classified into six groups based on the reperfusion treatment and early (within 24 hours) AT from rt-PA treatment. Safety outcomes were compared among the groups. RESULTS: A total of 155 patients (35 women [23%], median age 74 [IQR 66-79] years; NIHSS score 3 [1-10]) were included in the present study. Of these, 73 (47%) received no reperfusion therapy, 24 (15%) received rt-PA treatment and early AT, seven (6%) received rt-PA without early AT, 26 (17%) received EVT only, six (4%) received both rt-PA and EVT without early AT, and 19 (12%) received rt-PA and EVT with early AT. AT was administered a median of 3.9 (1.6-8.0) hours after rt-PA in patients with rt-PA+EVT with early AT. AT within 24 hours after rt-PA and EVT treatment did not increase hemorrhagic complications (p > 0.05 for all). CONCLUSION: In this retrospective analyses, early AT administration for patients with hyperacute stroke due to LAA treated with rt-PA plus EVT did not increase hemorrhagic events.

Differential effects of age on human striatal adenosine A1 and A(2A) receptors.

The aim of this study was to investigate the effect of age on the distribution of adenosine A1 receptors (A1Rs) and adenosine A(2A) receptors (A(2A)Rs) in the striatum of healthy subjects using PET imaging with 8-dicyclopropylmethyl-1-[¹¹C]methyl-3-propylxanthine ([¹¹C]MPDX) and [7-methyl-¹¹C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([¹¹C]TMSX), respectively. We recruited 8 young (22.0 ± 1.7 years) and 10 elderly (65.4 ± 7.6 years) volunteers to undergo [¹¹C]MPDX PET scanning, and 11 young (22.7 ± 2.7 years) and six elderly (60.7 ± 8.5 years) volunteers to undergo [¹¹C]TMSX PET scanning. A dynamic series of decay-corrected PET scans was performed for 60 min following injection of [¹¹C]MPDX or [¹¹C]TMSX. We calculated the binding potential (BP(ND) ) of [¹¹C]MPDX and distribution volume ratio (DVR) of [¹¹C]TMSX in the striatum. The BP(ND) of [¹¹C]MPDX was significantly lower in elderly than in young subjects, both in the putamen and head of the caudate nucleus. The BP(ND) was negatively correlated with age in both the putamen and the head of the caudate nucleus. However, no difference was found between the DVR of [¹¹C]TMSX in the striata of young and elderly subjects, nor was there a correlation between age and the DVR of [¹¹C]TMSX. The effect of age on the distribution of A1Rs in the human striatum described herein is similar to previous reports of age-related decreases in dopamine D1 and D2 receptors. Unlike A1Rs, however, this study suggests that the distribution of A(2A) Rs does not change with age.