Lower serum uric acid and impairment of right cerebral hemisphere structural brain networks are related to depressive symptoms in cerebral small vessel disease: A cross-sectional study.

Cerebral small vessel disease (SVD) may be associated with an increased risk of depressive symptoms. Serum uric acid (SUA), an antioxidant, may be involved in the occurrence and development of depressive symptoms, but the mechanism remains unknown. Moreover, the relationship between structural brain networks and SUA has not been explored. This study examined the relationship between SUA and depressive symptoms in patients with SVD using graph theory analysis. We recruited 208 SVD inpatients and collected fasting blood samples upon admission. Depressive symptoms were assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24). Magnetic resonance imaging was used to evaluate SVD, and diffusion tensor images were used to analyze structural brain networks using graph theory. Patients with depressive symptoms (n = 34, 25.76%) compared to those without (334.53 vs 381.28 µmol/L, p = 0.017) had lower SUA levels. Graph theoretical analyses showed a positive association of SUA with betweenness centrality, nodal efficiency, and clustering coefficients and a negative correlation with the shortest path length in SVD with depressive symptoms group. HAMD scores were significantly associated with nodal network metrics in the right cerebral hemisphere. Our findings suggested that lower SUA levels are significantly associated with disrupted structural brain networks in the right cerebral hemisphere of patients with SVD who have depressive symptoms.

Cerebral asymmetry in adult Macaca fascicularis as revealed by voxel-based MRI and DTI analysis.

Investigating cerebral asymmetries in non-human primates would facilitate to understand the evolutional traits of the human brain specialization related to language and other high-level cognition. However, brain asymmetrical studies of monkeys produced controversial results. Here, we investigated the cerebral asymmetries using a combination of the optimized voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) protocols in monkeys. The study-specific MRI and DTI-based templates were created in 66 adult Macaca fascicularis, and the asymmetrical index of grey and white matter was subsequently examined. The VBM analysis detected the well-known frontal and occipital petalias and confirmed the presence of leftward asymmetry in the ventral frontal cortex. A marked leftward asymmetry of anterior superior temporal gyrus but not posterior portion were found. We also identified grey matter asymmetries in some regions that were not previously reported including rightward anterior cingulate, insular cortex and thalamus, and leftward caudate. In contrast, the results of TBSS analysis for the first time revealed the robust leftwards asymmetries of corpus callosum (splenium and body), internal/external capsule, and white matter in middle temporal gyrus, adjacent thalamus and amygdala whereas the rightwards in uncinate fasciculus, posterior thalamic radiation and cerebral peduncle. These findings provide robust evidence of grey and white matter asymmetries in the brain of monkeys, which may extend the understanding of brain evolution in cerebral specialization.

Plaque characteristics associated with failure of primary balloon angioplasty for intracranial atherosclerotic stenosis: a retrospective study.

BACKGROUND: Primary balloon angioplasty (PBA) is an alternative treatment approach for intracranial atherosclerotic stenosis (ICAS); however, its efficacy may be compromised by arterial dissection or early elastic recoil after balloon dilation. This study aimed to explore the association between plaque characteristics on high-resolution magnetic resonance vessel wall imaging (HR-VWI) and failure of PBA for ICAS. METHODS: We conducted a retrospective analysis of 113 patients with ICAS who underwent HR-VWI before endovascular treatment. Based on the presence of arterial dissection or early elastic recoil post-balloon dilation, patients were classified into the failed PBA (FPBA) group or the successful PBA (SPBA) group. Clinical and baseline HR-VWI characteristics were compared between the two groups. Multivariable analysis was used to investigate plaque features associated with the failure of PBA. RESULTS: The FPBA and SPBA groups comprised 74 and 39 patients, respectively. Plaque eccentricity (83.78% vs 46.15%, P<0.001), negative remodeling (90.54% vs 48.72%, P<0.001), remodeling index (median 0.73 vs 0.90, P=0.001), and intraplaque hemorrhage (31.08% vs 5.13%, P=0.002) differed significantly between the FPBA and SPBA groups. Multivariable analysis indicated that higher frequency of plaque eccentricity (OR 14.03, 95% CI 3.42 to 57.62, P<0.001) and negative remodeling (OR 6.11, 95% CI 1.22 to 30.71, P=0.028) were independently associated with failure of PBA. CONCLUSION: Our findings showed that failure of PBA was associated with plaque eccentricity and negative remodeling. Analysis of plaque characteristics on baseline HR-VWI holds potential value for identifying arterial dissection or early elastic recoil after angioplasty in patients with ICAS.

Certification of stroke centers at primary hospitals and the improvement of thrombolysis n South China during 2020-2022.

INTRODUCTION: IVT use declined globally in 2020 due to the Corona Virus Disease 2019 (COVID-19) pandemic, but it increased in South China. This study was conducted to evaluate the association of establishing Stroke Prevention Centers (SPCs) at primary hospitals with IVT increase in South China. MATERIALS AND METHODS: We conducted a longitudinal observational study across 336 hospitals in 114 areas in South China during 2020-2022. Data regarding certified stroke centers, IVT volumes, and IVT rates were collected. Correlations between IVT rates and the number or density of stroke centers were accessed. IVT use was compared among areas with different levels of stroke centers or on different certification process. RESULTS: During 2020-2022, there were 83, 125, and 152 stroke centers, with 26, 65, and 92 SPCs, respectively. IVT therapies were 12,795, 17,266, and 20,411, representing a 29.8% increase/year (all p < 0.001). IVT rates increased from 7.2% in 2020 to 8.8% and 10.4% in 2021 and 2022, demonstrating a 22.2% increase/year (all p < 0.001). IVT rates correlated with the number and density of SPCs (all p < 0.05). IVT rates were higher in areas equipped with SPCs than in those without stroke centers (all p < 0.05). IVT rates consistently increased during the SPC certification process from 1 year before through the certification and subsequent maintenance (both p < 0.05). DISCUSSION AND CONCLUSION: Well-organised SPCs and IVT therapy demonstrated substantial increase during the 3-year period. Certification of SPCs at primary hospitals is associated with improved IVT therapy in South China even with city lockdown during COVID-19 pandemic.

Loss of SARM1 ameliorates secondary thalamic neurodegeneration after cerebral infarction.

Ischemic stroke causes secondary neurodegeneration in the thalamus ipsilateral to the infarction site and impedes neurological recovery. Axonal degeneration of thalamocortical fibers and autophagy overactivation are involved in thalamic neurodegeneration after ischemic stroke. However, the molecular mechanisms underlying thalamic neurodegeneration remain unclear. Sterile /Armadillo/Toll-Interleukin receptor homology domain protein (SARM1) can induce Wallerian degeneration. Herein, we aimed to investigate the role of SARM1 in thalamic neurodegeneration and autophagy activation after photothrombotic infarction. Neurological deficits measured using modified neurological severity scores and adhesive-removal test were ameliorated in Sarm1-/- mice after photothrombotic infarction. Compared with wild-type mice, Sarm1-/- mice exhibited unaltered infarct volume; however, there were markedly reduced neuronal death and gliosis in the ipsilateral thalamus. In parallel, autophagy activation was attenuated in the thalamus of Sarm1-/- mice after cerebral infarction. Thalamic Sarm1 re-expression in Sarm1-/- mice increased thalamic neurodegeneration and promoted autophagy activation. Auotophagic inhibitor 3-methyladenine partially alleviated thalamic damage induced by SARM1. Moreover, autophagic initiation through rapamycin treatment aggravated post-stroke neuronal death and gliosis in Sarm1-/- mice. Taken together, SARM1 contributes to secondary thalamic neurodegeneration after cerebral infarction, at least partly through autophagy inhibition. SARM1 deficiency is a potential therapeutic strategy for secondary thalamic neurodegeneration and functional deficits after stroke.

Efficacy and safety of agomelatine versus SSRIs/SNRIs for post-stroke depression: a systematic review and meta-analysis of randomized controlled trials.

Agomelatine is effective in the treatment of depression, but its effect for post-stroke depression (PSD) remains unclear. This study was conducted to compare the efficacy and safety of agomelatine versus SSRIs/SNRIs in treating PSD. We systematically searched Embase, PubMed, Cochrane Library, WanFang Data, China National Knowledge Infrastructure, and Cqvip databases for double-blind randomized controlled studies comparing the efficacy and safety of agomelatine versus SSRIs/SNRIs for PSD until December 2022. The primary efficacy endpoint was the Hamilton Depression Rating Scale (HAMD) score, and the primary safety endpoint was the incidence of overall adverse reactions. Nine studies comprising 857 patients with PSD were included. After 6-12 weeks of treatment, the HAMD score ( P  = 0.16) and the overall response rates ( P  = 0.20) in the agomelatine group were comparable to that in the SSRIs/SNRIs group. Participants treated with agomelatine achieved higher Barthel Index scores compared with the SSRIs/SNRIs group ( P  = 0.02). There was a significantly lower incidence of overall adverse reactions ( P  = 0.008) and neurological adverse reactions ( P  < 0.0001) in the agomelatine group. The efficacy of agomelatine for treating PSD is probably comparable to that of SSRIs/SNRIs, and it may improve stroke outcomes with better safety.

Microvascular dysfunction associated with unfavorable venous outflow in acute ischemic stroke patients.

Unfavorable venous outflow (VO) is associated with cerebral edema, which represents microvascular dysfunction. This study estimated the relationship between VO and microvascular function in acute ischemic stroke patients. We retrospectively included 102 MCA/ICA occluded patients with anterior circulation infarction who underwent reperfusion therapy between July 2017 and April 2022. Unfavorable VO was defined as a cortical vein opacification score of 0-3 and favorable VO as that of 4-6. The clinical characteristics, collateral status, microvascular integrity, and outcomes were compared between patients with favorable and unfavorable VO. Multivariate analysis and receiver operator characteristic (ROC) analysis were used. The patients with unfavorable VO had higher extravascular-extracellular volume fraction (Ve) in the infarct core and a lower percentage of robust arterial collateral circulation. ROC analysis revealed that Ve in the infarct core predicts unfavorable VO (AUC = 0.67, sensitivity = 65.08%, specificity = 69.23%). The higher Ve in the infarct core (odds ratio = 1.011, 95% CI = 1.000-1.021, P = 0.046) and poor arterial collateral flow (odds ratio = 0.102, 95% CI = 0.032-0.327, P < 0.001) were independent predictors of unfavorable VO. This suggests that microvascular dysfunction may be one of the mechanisms underlying impaired VO.

Remote cortical atrophy and language outcomes after chronic left subcortical stroke with aphasia.

Objective: Subcortical stroke can cause a variety of language deficits. However, the neural mechanisms underlying subcortical aphasia after stroke remain incompletely elucidated. We aimed to determine the effects of distant cortical structures on aphasia outcomes and examine the correlation of cortical thickness measures with connecting tracts integrity after chronic left subcortical stroke. Methods: Thirty-two patients and 30 healthy control subjects underwent MRI scanning and language assessment with the Western Aphasia Battery-Revised (WAB-R) subtests. Among patients, the cortical thickness in brain regions that related to language performance were assessed by the FreeSurfer software. Fiber tracts connecting the identified cortical regions to stroke lesions were reconstructed to determine its correlations with the cortical thickness measures across individual patient. Results: Cortical thickness in different parts of the left fronto-temporo-parietal (FTP) regions were positively related to auditory-verbal comprehension, spontaneous speech and naming/word finding abilities when controlling for key demographic variables and lesion size. Cortical thickness decline in the identified cortical regions was positively correlated with integrity loss of fiber tracts connected to stroke lesions. Additionally, no significant difference in cortical thickness was found across the left hemisphere between the subgroup of patients with hypoperfusion (HP) and those without HP at stroke onset. Conclusions: These findings suggest that remote cortical atrophy independently predicts language outcomes in patients with chronic left subcortical stroke and aphasia and that cortical thinning in these regions might relate to integrity loss of fiber tracts connected to stroke lesions.

Silent brain infarction is associated with carotid siphon calcification in ischemic stroke patients.

BACKGROUND: Silent brain infarction (SBI) had a higher prevalence in ischemic stroke patients than healthy population. Intracranial artery calcification, as the important component of atherosclerosis, is a known risk factor of ischemic stroke. Whether it is also the risk factor of SBI is uncertain. We aimed to assess the association between SBI and carotid siphon calcification (CSC) in ischemic stroke patients. METHODS: We retrospectively collected consecutive data of acute ischemic stroke patients with and without SBI by Magnetic Resonance Imaging (MRI) and calcification using non-contrast Computerized Tomography (NCCT). We used a histopathologically validated method to score the circularity, thickness, and morphology of calcification. Clinical characteristics, prevalence and pattern (intimal and medial) of CSC were compared between patients with and without SBI. The association of CSC and SBI was investigated by logistic regression analysis. RESULTS: Totally, 303 acute ischemic stroke patients were enrolled, of whom 260 (85.8%) had CSC. Patients with SBI were older (64.5 ± 10.4 years vs. 61.3 ± 12.1 years, P = 0.032), had a higher proportion of hypertension (77.5% vs. 65.7%, P = 0.035). Of the 260 CSC patients, there's no significant difference except for hyperlipidemia between patients with SBI and without SBI. The prevalence of intimal pattern of CSC was higher in those with SBI (adjusted odds ratio 2.42, 95% CI 1.219-4.794). CONCLUSIONS: Patients with SBI at acute phase of ischemic stroke have more risk factors than mentioned previously. SBI associated with the intimal pattern of CSC which relate to the atherosclerosis process in symptomatic ischemic stroke patients.

High on-treatment platelet reactivity is associated with poor outcomes after ischemic stroke: A meta-analysis.

OBJECTIVES: High on-treatment platelet reactivity (HTPR) determined by platelet function assays is present in certain patients with ischemic stroke or transient ischemic attack (TIA). However, it is unclear whether HTPR is associated with poor clinical outcomes. Our study aimed to investigate the relationship of HTPR with recurrent vascular events in ischemic stroke or TIA. METHODS: Pubmed (MEDLINE), EMBASE, and Cochrane Library were searched for eligible studies from inception to January 1, 2022. Stata 17.0 software was used to calculate the risk ratio (RR). Subgroup and sensitivity analyses were conducted to assess the source of heterogeneity. A random-effects model was used when heterogeneity was present. Primary endpoint of the meta-analysis was the risk ratio of recurrent vascular events in HTPR Patients. While stroke and TIA, all-cause death, early neurological deterioration, early new ischemic lesions, and stroke severity measured by National Institute of Health Stroke Scale (NIHSS) scores at admission were also pooled. RESULTS: Thirty articles (7995 patients) were eligible including 28 cohort studies and 2 prospective case-control studies. The prevalence of HTPR varied from 5.9% to 60%. HTPR was associated with an increased risk of recurrent vascular events (RR = 2.94, 95% CI 2.04-4.23), stroke recurrence (RR = 2.05; 95% CI 1.43-2.95), and all-cause mortality (RR = 2.43; 95% CI 1.83-3.22). Subgroup analysis showed that HTPR determined by optical aggregometry, Verify-Now system and 11dh TXB2 is related to a higher risk of recurrent vascular events (RR = 3.53, 95% CI 1.51-9.40; RR = 2.16, 95% CI 1.02-4.56; RR = 3.76, 95% CI 1.51-9.40, respectively). Moreover, patients with HTPR had an increased incidence of early neurological deterioration (RR = 2.75; 95% CI 1.76-4.30) and higher NIHSS scores at admission (Mean difference 0.19, 95% CI 0.01-0.36). CONCLUSIONS: This meta-analysis demonstrates HTPR is associated with higher risk of recurrent vascular events, early neurological deterioration and increased severity in patients with ischemic stroke and TIA. HTPR measured by platelet function assays may guide the use of antiplatelet agents in ischemic stroke and TIA.

Glucose-6-phosphate dehydrogenase deficiency and intracranial atherosclerotic stenosis in stroke patients.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic stenosis (ICAS) is a major cause of stroke in Asian countries. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a hereditary enzyme defect prevalent in Asian countries, has been associated with atherosclerotic cardiovascular disease and worse poststroke outcomes. However, the impact of G6PD deficiency on ICAS remains unclear. We aimed to compare the risk of ICAS in stroke patients with and without G6PD deficiency in a Chinese cohort. METHODS: We prospectively and consecutively recruited stroke patients from four centers in China. All patients received intracranial artery assessment by magnetic resonance/computed tomography angiography or digital subtraction angiography, as well as G6PD enzyme evaluation. The prevalence, burden, and characteristics of ICAS were compared between patients with and without G6PD deficiency using multivariate regression analysis. RESULTS: Among 1593 patients, 116 (63.7%) of 182 patients with G6PD deficiency and 714 (50.6%) of 1411 patients with normal G6PD levels were identified as ICAS. Age, hypertension, diabetes, and G6PD deficiency were independent predictors of ICAS. Among patients with ICAS, G6PD-deficient individuals were more likely to have multiple (≥2 segments) intracranial stenosis (odds ratio [OR] = 1.87, 95% confidence interval [CI] = 1.25-2.81, p = 0.002). G6PD deficiency increased the risk of ICAS in patients who were male (OR = 1.82, 95% CI = 1.24-2.66, p = 0.002), aged ≥70 years (OR = 2.40, 95% CI = 1.33-4.31, p = 0.004), or hypertensive (OR = 1.88, 95% CI = 1.28-2.77, p = 0.001). CONCLUSIONS: Stroke patients with G6PD deficiency have a higher prevalence and ICAS burden than those with normal G6PD, particularly those who are male, older, and hypertensive.

Retrospective Comparative Analysis of Clinical and Imaging Features of Craniocervical Artery Dissection: Spontaneous CAD vs. Minor Traumatic CAD.

Background and Objectives: Craniocervical artery dissection (CAD) is the most common cause of ischemic stroke in young adults. The etiologies of CAD can be classified into three types, such as spontaneous (sCAD), minor traumatic (mtCAD), and genetic origin. Recent studies indicated that clinical presentations and imaging features could guide management and inform prognosis. This retrospective analysis sought to compare the clinical and imaging features of sCAD vs. mtCAD in providing evidence-based advice on medical treatment, functional rehabilitation, secondary stroke prevention, and prognosis, ultimately formulating clinical guidelines in managing CAD. Methods: In total, 148 patients with CAD were identified from the medical records database and subdivided into sCAD and mtCAD based on the clinical presentations and imaging features. A retrospective comparative analysis was performed according to their clinical presentations and imaging features. Results: Patients with mtCAD are significantly younger than sCAD with 120 cases of sCAD average aged 43.61 ± 12.75, while 28 cases of mtCAD average aged 35.68 ± 14.54. Patients with mtCAD had more cases of neck pain compared to sCAD. Patients with mtCAD had more cases of CAD at extracranial locations compared to sCAD. Patients with mtCAD had more cases of multiple site dissection compared to sCAD. Double lumen and intramural haematoma are the most common imaging findings with mtCAD patients having statistical significantly more cases of intramural haematoma and long tapering stenosis. Conclusion: Patients with mtCAD were presented at a much younger age with symptoms of neck pain compared to sCAD. Patients with mtCAD predominantly presented at extracranial sites with more prominent features of multiple site dissection, intramural haematoma, and long tapering stenosis. These clinical and imaging features can translate into clinical practice guidelines for patients with CAD to improve the optimal functional outcome and reduce both morbidity and mortality.

RTN4/Nogo-A-S1PR2 negatively regulates angiogenesis and secondary neural repair through enhancing vascular autophagy in the thalamus after cerebral cortical infarction.

Cerebral infarction induces angiogenesis in the thalamus and influences functional recovery. The mechanisms underlying angiogenesis remain unclear. This study aimed to investigate the role of RTN4/Nogo-A in mediating macroautophagy/autophagy and angiogenesis in the thalamus following middle cerebral artery occlusion (MCAO). We assessed secondary neuronal damage, angiogenesis, vascular autophagy, RTN4 and S1PR2 signaling in the thalamus. The effects of RTN4-S1PR2 on vascular autophagy and angiogenesis were evaluated using lentiviral and pharmacological approaches. The results showed that RTN4 and S1PR2 signaling molecules were upregulated in parallel with angiogenesis in the ipsilateral thalamus after MCAO. Knockdown of Rtn4 by siRNA markedly reduced MAP1LC3B-II conversion and levels of BECN1 and SQSTM1 in vessels, coinciding with enhanced angiogenesis in the ipsilateral thalamus. This effect coincided with rescued neuronal loss of the thalamus and improved cognitive function. Conversely, activating S1PR2 augmented vascular autophagy, along with suppressed angiogenesis and aggravated neuronal damage of the thalamus. Further inhibition of autophagic initiation with 3-methyladenine or spautin-1 enhanced angiogenesis while blockade of lysosomal degradation by bafilomycin A1 suppressed angiogenesis in the ipsilateral thalamus. The control of autophagic flux by RTN4-S1PR2 was verified in vitro. Additionally, ROCK1-BECN1 interaction along with phosphorylation of BECN1 (Thr119) was identified in the thalamic vessels after MCAO. Knockdown of Rtn4 markedly reduced BECN1 phosphorylation whereas activating S1PR2 increased its phosphorylation in vessels. These results suggest that blockade of RTN4-S1PR2 interaction promotes angiogenesis and secondary neural repair in the thalamus by suppressing autophagic activation and alleviating dysfunction of lysosomal degradation in vessels after cerebral infarction.Abbreviations: 3-MA: 3-methyladenine; ACTA2/ɑ-SMA: actin alpha 2, smooth muscle, aorta; AIF1/Iba1: allograft inflammatory factor 1; BafA1: bafilomycin A1; BMVECs: brain microvascular endothelial cells; BrdU: 5-bromo-2'-deoxyuridine; CLDN11/OSP: claudin 11; GFAP: glial fibrillary acidic protein; HUVECs: human umbilical vein endothelial cells; LAMA1: laminin, alpha 1; MAP2: microtubule-associated protein 2; MBP2: myelin basic protein 2; MCAO: middle cerebral artery occlusion; PDGFRB/PDGFRß: platelet derived growth factor receptor, beta polypeptide; RECA-1: rat endothelial cell antigen-1; RHOA: ras homolog family member A; RHRSP: stroke-prone renovascular hypertensive rats; ROCK1: Rho-associated coiled-coil containing protein kinase 1; RTN4/Nogo-A: reticulon 4; RTN4R/NgR1: reticulon 4 receptor; S1PR2: sphingosine-1-phosphate receptor 2; SQSTM1: sequestosome 1.

Machine Learning for Predicting Motor Improvement After Acute Subcortical Infarction Using Baseline Whole Brain Volumes.

Background. Neuroimaging biomarkers are valuable predictors of motor improvement after stroke, but there is a gap between published evidence and clinical usage. Objective. In this work, we aimed to investigate whether machine learning techniques, when applied to a combination of baseline whole brain volumes and clinical data, can accurately predict individual motor outcome after stroke. Methods. Upper extremity Fugl-Meyer Assessments (FMA-UE) were conducted 1 week and 12 weeks, and structural MRI was performed 1 week, after onset in 56 patients with subcortical infarction. Proportional recovery model residuals were employed to assign patients to proportional and poor recovery groups (34 vs 22). A sophisticated machine learning scheme, consisting of conditional infomax feature extraction, synthetic minority over-sampling technique for nominal and continuous, and bagging classification, was employed to predict motor outcomes, with the input features being a combination of baseline whole brain volumes and clinical data (FMA-UE scores). Results. The proposed machine learning scheme yielded an overall balanced accuracy of 87.71% in predicting proportional vs poor recovery outcomes, a sensitivity of 93.77% in correctly identifying poor recovery outcomes, and a ROC AUC of 89.74%. Compared with only using clinical data, adding whole brain volumes can significantly improve the classification performance, especially in terms of the overall balanced accuracy (from 80.88% to 87.71%) and the sensitivity (from 92.23% to 93.77%). Conclusions. Experimental results suggest that a combination of baseline whole brain volumes and clinical data, when equipped with appropriate machine learning techniques, may provide valuable information for personalized rehabilitation planning after subcortical infarction.

Population-Average Brain Templates and Application to Automated Voxel-Wise Analysis Pipelines for Cynomolgus Macaque.

The growing number of neuroimaging studies of cynomolgus macaques require extending existing templates to facilitate species-specific application of voxel-wise neuroimaging methodologies. This study aimed to create population-averaged structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) templates for the cynomolgus macaques and apply the templates in fully automated voxel-wise analyses. We presented the development of symmetric and asymmetric MRI and DTI templates from a sample of 63 young male cynomolgus monkeys with the use of optimized template creation approaches. We also generated the associated average tissue probability maps and Diffeomorphic Anatomical Registration using Exponentiated Lie Algebra templates for use with the Statistical Parametric Mapping (SPM), as well as the average fractional anisotropy/skeleton targets for incorporation into tract-based spatial statistics (TBSS) framework. Both asymmetric and symmetric templates in a standardized coordinate space demonstrated low bias and high contrast. Fully automated processing using SPM was accomplished for all native MRI datasets and demonstrated outstanding performance regarding skull-stripping, segmentation, and normalization when using the MRI templates. Automated normalization to the DTI template was excellently achieved for all native DTI images using the TBSS pipeline. The cynomolgus MRI and DTI templates are anticipated to provide a common platform for precise single-subject data analysis and facilitate comparison of neuroimaging findings in cynomolgus monkeys across studies and sites. It is also hoped that the procedures of template creation and fully-automated voxel-wise frameworks will provide a straightforward avenue for investigating brain function, development, and neuro-psychopathological disorders in non-human primate models.

Association between aspirin-induced hemoglobin decline and outcome after acute ischemic stroke in G6PD-deficient patients.

AIMS: The risk of hemoglobin decline induced by low-dose aspirin in glucose-6-phosphate dehydrogenase (G6PD) deficiency remains unknown, and its influence on stroke outcome remains to be investigated. This study aimed to evaluate the effect of G6PD deficiency on hemoglobin level during aspirin treatment and its association with outcome after acute ischemic stroke. METHODS: In total, 279 patients (40 G6PD-deficient and 239 G6PD-normal) with acute ischemic stroke treated with aspirin 100 mg/day from a cohort study were examined. The primary safety endpoint was a hemoglobin decline ≥25 g/L or 25% from baseline within 14 days after aspirin treatment. Poor outcomes were defined as a modified Rankin Scale score ≥2 at 3 months. The χ2 test was used to compare stroke outcomes, and multivariate logistic regression analyses were performed to analyze the association between hemoglobin level and outcomes. RESULTS: The G6PD-deficient group had lower baseline hemoglobin and tended to develop comorbid pulmonary infection more frequently (p < 0.05). The proportion of patients with hemoglobin decline ≥25 g/L or 25% from baseline (15.0% vs. 3.3%; p = 0.006) and anemia (30.0% vs. 14.6%; p = 0.016) after aspirin treatment was higher in the G6PD-deficient group, which was accompanied by a more significant bilirubin increase. The rate of poor functional outcomes at 3 months after acute ischemic stroke was higher in the G6PD-deficient group (Risk ratio = 1.31 [95% confidence interval (CI) = 1.10-1.56]; p = 0.017). Confounder-adjusted analysis showed that lower hemoglobin levels (odds ratio = 0.98 [95% CI = 0.96-0.99]; adjusted p = 0.009) increased the risk of poor functional outcomes. CONCLUSION: Hemoglobin decrease with bilirubin increase after aspirin treatment in patients with G6PD deficiency suggests hemolysis, which may influence stroke prognosis. The risk of hemoglobin decline should be carefully monitored in G6PD-deficient patients with ischemic stroke taking aspirin.

Longitudinal changes in the inferior cerebellar peduncle and lower limb motor recovery following subcortical infarction.

BACKGROUND: The cerebellum receives afferent signals from spinocerebellar pathways regulating lower limb movements. However, the longitudinal changes in the spinocerebellar pathway in the early stage of unilateral supratentorial stroke and their potential clinical significance have received little attention. METHODS: Diffusion tensor imaging and Fugl-Meyer assessment of lower limb were performed 1, 4, and 12 weeks after onset in 33 patients with acute subcortical infarction involving the supratentorial areas, and in 33 healthy subjects. We evaluated group differences in diffusion metrics in the bilateral inferior cerebellar peduncle (ICP) and analyzed the correlation between ICP diffusion metrics and changes to the Fugl-Meyer scores of the affected lower limb within 12 weeks after stroke. RESULTS: Significantly decreased fractional anisotropy and increased mean diffusivity were found in the contralesional ICP at week 12 after stroke compared to controls (all P < 0.01) and those at week 1 (all P < 0.05). There were significant fractional anisotropy decreases in the ipsilesional ICP at week 4 (P = 0.008) and week 12 (P = 0.004) compared to controls. Both fractional anisotropy (rs = 0.416, P = 0.025) and mean diffusivity (rs = -0.507, P = 0.005) changes in the contralesional ICP correlated with changes in Fugl-Meyer scores of the affected lower limb in all patients. CONCLUSIONS: Bilateral ICP degeneration occurs in the early phase of supratentorial stroke, and diffusion metric values of the contralesional ICP are useful indicators of affected lower limb function after supratentorial stroke.

Is Cerebral Amyloid-ß Deposition Related to Post-stroke Cognitive Impairment?

Approximately two-thirds of ischemic stroke patients suffer from different levels of post-stroke cognitive impairment (PSCI), but the underlying mechanisms of PSCI remain unclear. Cerebral amyloid-ß (Aß) deposition, a pathological hallmark of Alzheimer's disease, has been discovered in the brains of stroke patients in some autopsy studies. However, less is known about the role of Aß pathology in the development of PSCI. It is hypothesized that cerebral ischemic injury may lead to neurotoxic Aß accumulation in the brain, which further induces secondary neurodegeneration and progressive cognitive decline after stroke onset. In this review, we summarized available evidence from pre-clinical and clinical studies relevant to the aforementioned hypothesis. We found inconsistency in the results obtained from studies in rodents, nonhuman primates, and stroke patients. Moreover, the causal relationship between post-stroke cerebral Aß deposition and PSCI has been uncertain and controversial. Taken together, evidence supporting the hypothesis that brain ischemia induces cerebral Aß deposition has been insufficient so far. And, there is still no consensus regarding the contribution of cerebral amyloid pathology to PSCI. Other non-amyloid neurodegenerative mechanisms might be involved and remain to be fully elucidated.

Safety and efficacy of low-dose aspirin in ischemic stroke patients with different G6PD conditions.

BACKGROUND AND PURPOSE: Aspirin is the first recommended antiplatelet agent to prevention secondary stroke, but its safety and efficacy in stroke patients with glucose-6-phosphate dehydrogenase deficiency remain unclear. We sought to evaluate its safety and efficacy in ischemic stroke patients with and without glucose-6-phosphate dehydrogenase deficiency. METHODS: Patients with ischemic stroke receiving aspirin (100 mg/day) for three months were recruited for a multicenter, prospective, cohort study. Blood glucose-6-phosphate dehydrogenase activity was examined after stroke. Safety outcomes including acute hemolysis, moderate-to-severe bleeding, and death (vascular, all-cause), and efficacy outcome indicated as stroke recurrence were evaluated at three months. Risk factors associated with moderate-to-severe bleeding and all-cause death were determined using multivariate or Cox regression analysis. RESULTS: Among the included 1121 patients, 81 of 130 glucose-6-phosphate dehydrogenase deficient and 576 of 991 glucose-6-phosphate dehydrogenase normal patients received aspirin for three months. Acute hemolysis was observed in one of the glucose-6-phosphate dehydrogenase deficient and in none of the glucose-6-phosphate dehydrogenase normal patients (p = 0.876). The rates of moderate-to-severe bleeding were 2.5% and 0.3% (p = 0.045), and the percentages of all-cause death were 6.2% and 1.4% (p = 0.008) in the glucose-6-phosphate dehydrogenase deficient and glucose-6-phosphate dehydrogenase normal patients. Stroke recurrence rate was similar in the two groups (2.5% vs. 1.7%; p = 0.608). Glucose-6-phosphate dehydrogenase deficiency was significantly associated with increased risk of moderate-to-severe bleeding (adjust p = 0.048) and all-cause death during aspirin use (adjust p = 0.008). CONCLUSIONS: Long-term low-dose aspirin therapy might relate to worse safety outcomes in patients with glucose-6-phosphate dehydrogenase deficiency and large clinical trials are needed to further confirm these findings.

Predisposing factors and radiological features in patients with internal carotid artery dissection or vertebral artery dissection.

BACKGROUND: Cervicocerebral artery dissection is an important cause of ischemic stroke in young and middle-aged individuals. However, very few studies have compared the differential features between internal carotid artery dissection (ICAD) and vertebral artery dissection (VAD), including both cervical and intracranial artery dissections. We conducted a study to investigate the predisposing factors and radiological features in patients with ICAD or VAD. METHODS: All cases diagnosed with cervicocerebral artery dissection, ICAD, or VAD were identified through a medical records database, between January 2010 and January 2020. Baseline characteristics, predisposing factors, and radiological features of ICAD versus VAD were compared. RESULTS: A total of 140 patients with cervicocerebral artery dissection were included in the study, including 84 patients in the ICAD group and 56 in the VAD group. The mean age of patients in the ICAD and VAD groups was 43.37 ± 14.01 and 41.00 ± 12.98 years old, respectively. Patients with ICAD were more likely to be men compared with VAD (85.71% vs. 67.86%, p = 0.012). The frequency of hypertension, diabetes, smoking, drinking, and cervical trauma did not differ between ICAD and VAD. Dissections of ICAD were more frequently at the extracranial portions of the artery compared with those of VAD (70.24% vs. 44.64%, p = 0.003). In contrast, dissections of VAD were more common in the intracranial artery (55.36% vs. 29.76%, p = 0.003). Radiologically, double lumen (36.90% vs. 19.64%, p = 0.029) and intimal flap (11.90% vs. 1.79%, p = 0.029) were more frequently observed in ICAD than in VAD, and dissecting aneurysms were less frequent (13.10% vs. 26.79%, p = 0.041). CONCLUSIONS: The distributions of cervical and intracranial artery dissections were different between ICAD and VAD. The frequencies of radiological features detected in patients with ICAD and VAD also differed.