High-frequency repetitive transcranial magnetic stimulation (rTMS) protects against ischemic stroke by inhibiting M1 microglia polarization through let-7b-5p/HMGA2/NF-κB signaling pathway.

BACKGROUND: Microglia assume opposite phenotypes in response to ischemic brain injury, exerting neurotoxic and neuroprotective effects under different ischemic stages. Modulating M1/M2 polarization is a potential therapy for treating ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS) held the capacity to regulate neuroinflammation and astrocytic polarization, but little is known about rTMS effects on microglia. Therefore, the present study aimed to examine the rTMS influence on microglia polarization and the underlying possible molecular mechanisms in ischemic stroke models. METHODS: Previously reported 10 Hz rTMS protocol that regulated astrocytic polarization was used to stimulate transient middle cerebral artery occlusion (MCAO) rats and oxygen and glucose deprivation/reoxygenation (OGD/R) injured BV2 cells. Specific expression levels of M1 marker iNOS and M2 marker CD206 were measured by western blotting and immunofluorescence. MicroRNA expression changes detected by high-throughput second-generation sequencing were validated by RT-PCR and fluorescence in situ hybridization (FISH) analysis. Dual-luciferase report assay and miRNA knock-down were applied to verify the possible mechanisms regulated by rTMS. Microglia culture medium (MCM) from different groups were collected to measure the TNF-α and IL-10 concentrations, and detect the influence on neuronal survival. Finally, TTC staining and modified Neurological Severity Score (mNSS) were used to determine the effects of MCM on ischemic stroke volume and neurological functions. RESULTS: The 10 Hz rTMS inhibited ischemia/reperfusion induced M1 microglia and significantly increased let-7b-5p level in microglia. HMGA2 was predicted and proved to be the target protein of let-7b-5p. HMGA2 and its downstream NF-κB signaling pathway were inhibited by rTMS. Microglia culture medium (MCM) collected from rTMS treated microglia contained lower TNF-α concentration but higher IL-10 concentration than no rTMS treated MCM, reducing ischemic volumes and neurological deficits of MCAO mice. However, knockdown of let-7b-5p by antagomir reversed rTMS effects on microglia phenotype and associated HMGA/NF-κB activation and neurological recovery. CONCLUSION: High-frequency rTMS could alleviate ischemic stroke injury through inhibiting M1 microglia polarization via regulating let-7b-5p/HMGA2/NF-κB signaling pathway in MCAO models.

Functional analysis of variants in DMD exon/intron 10 predicted to affect splicing.

Duchenne muscular dystrophy (DMD, MIM #310200) and Becker muscular dystrophy (BMD, MIM #300376) are X-linked recessive hereditary diseases caused by pathogenic variants in the DMD gene. Genetic testing of DMD identifies a certain number of variants of uncertain clinical significance (VUS) whose functional interpretations pose a challenge for gene-based diagnosis. To improve the accuracy of variant interpretation in public mutation repositories, we used computational tools to prioritize VUS and developed a cell-based minigene assay to confirm aberrant splicing. Using this procedure, we evaluated rare variants in exon and intron 10 of the DMD gene. We demonstrated that 16 variants, including both canonical and non-canonical splice sites, altered RNA splicing in variable patterns. Using the example of exon and intron 10 of the DMD gene, we demonstrated the utility of the in vitro minigene assay in the effective assessment of the spliceogenic effect for VUS identified in clinical practice and underlined the necessity of precise variant classification. This is the first systematic characterization of DMD splicing variants, besides, through our study, some undetermined variants are demonstrated to be pathogenic by altering RNA splicing of DMD.

Endovascular treatment of acute ischemic stroke due to anterior circulation large vessel occlusion beyond 6 hours: a real-world study in China.

BACKGROUND: We aimed to assess the safety and efficacy of endovascular treatment (EVT) in patients with anterior circulation emergent large vessel occlusion (ELVO) beyond 6 h from symptom onset in a real-world cohort of patients in China. METHODS: We retrospectively examined 305 patients with anterior circulation ELVO treated with EVT. Patients were divided into two groups: treated with known onset within 6 h (n = 238) and beyond 6 h (n = 67). Multivariable logistic regression and ordinal shift analyses were used to evaluate the associations between onset-to-groin puncture time and safety and efficacy outcomes. RESULTS: Treatment beyond 6 h was not associated with symptomatic intracranial hemorrhage within 48 h (sICH; odds ratio [OR] 2.03, 95% confidence interval [CI] 0.48-8.57, p = 0.334), in-hospital mortality (OR 1.95, 95% CI 0.48-7.91, p = 0.348), successful recanalization (modified Thrombolysis in Cerebral Infarction score 2b or 3; OR 0.73, 95% CI 0.31-1.73, p = 0.470), favorable functional outcome (modified Rankin Scale score 0-2; OR 0.55, 95% CI 0.25-1.23, p = 0.145), and functional improvement (modified Rankin Scale shift by 1-point decrease; common OR 0.80, 95%CI 0.45-1.42, p = 0.450) at 3 months compared with treatment within 6 h. Futher interaction analysis showed that stroke etiology did not modify the associations between onset-to-groin puncture time and outcomes (p > 0.05). CONCLUSIONS: In this real-world study, after careful assessment, EVT beyond 6 h from known stroke onset was safe, effective and had comparable short-term outcomes to EVT within 6 h.

Admission blood cell counts are predictive of stroke-associated infection in acute ischemic stroke patients treated with endovascular therapy.

Stroke-associated infection (SAI) is a major medical complication in acute ischemic stroke patients (AIS) treated with endovascular therapy (EVT). Three hundred thirty-three consecutive patients with AIS caused by a large vessel occlusion in the anterior circulation who received EVT (142 (42.6%) of them were given IV tPA as bridging therapy) and 337 AIS patients who received IV tPA only (non-EVT) were enrolled in the study and evaluated to determine the association of inflammatory factors on admission with SAI. Among the 333 AIS patients undergoing EVT, SAI occurred in 219 (65.8%) patients. Patients with SAI had higher baseline National Institutes of Health Stroke Scale (NIHSS) total scores, white blood cell (WBC) and neutrophil counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) than those without SAI (P < 0.05). The multivariable logistic regression analyses showed that older age in addition to higher diastolic blood pressure (DBP), NIHSS score, fasting blood glucose, WBC and neutrophil counts, NLR, and PLR were significantly associated with SAI (P < 0.05). However, these associations were not revealed in 337 non-EVT AIS patients. Furthermore, based on the inflammatory markers, we developed a nomogram that provided the opportunity for more accurate predictions (compared with conventional factors) and appeared a better prognostic tool for SAI according to the decision curve analysis. In summary, if proven externally valid, our nomogram that included WBC count, NLR, and PLR may be a useful tool for SAI prediction in clinical practice.

One-step analysis of brain perfusion and function for acute stroke patients after reperfusion: A resting-state fMRI study.

BACKGROUND: Resting-state functional magnetic resonance imaging (rs-fMRI) can noninvasively estimate the perfusion and function of the brain. PURPOSE: To investigate the perfusion and functional status using rs-fMRI in acute ischemic stroke (AIS) patients after reperfusion therapy. STUDY TYPE: Prospective. SUBJECTS: Twenty-five AIS patients who underwent dynamic susceptibility contrast (DSC) upon hospital admission and both rs-fMRI and DSC scans at 24 hours after reperfusion therapy. FIELD STRENGTH/SEQUENCE: 3T; DSC, rs-fMRI. ASSESSMENT: The time delay of the blood oxygenation level-dependent (BOLD) signal was calculated using time-shift-analysis (TSA) and compared with the time to peak (TTP) derived from the DSC. For patients who exhibited partial or complete reperfusion in the supratentorial hemisphere, we quantified the function of different regions (healthy tissue, reperfused tissue, not reperfused tissue) by using three rs-fMRI measurements (functional connectivity, the amplitude of low-frequency fluctuation [ALFF] and regional homogeneity [ReHo]). Correlations between the functional measurements and modified Rankin Scale (mRS) scores were calculated. STATISTICAL TESTS: Dice coefficient (DC) analysis, two-sample t-tests, Pearson correlation coefficient. RESULTS: Twelve patients who exhibited complete reperfusion on their TTP maps showed no time-delayed areas on the TSA maps. For the remaining 13 patients with partial reperfusion (5/13) or no reperfusion (8/13) on the TTP maps, the TSA detected comparable time-delayed areas. Eleven out of 13 patients showed moderate to good overlap (mean DC, 0.58 ± 0.1) between the TTP and TSA results. Fourteen patients were chosen for functional analyses and most patients (12/14) showed abnormal functional connectivity in the reperfused regions. The reperfused and not reperfused tissues had lower mean ReHo values than those of the healthy tissue (both P < 0.001). The mRS scores showed negative correlation with mean ReHo values of reperfused region (R = -0.523, P = 0.027). DATA CONCLUSION: rs-fMRI might be a useful way to estimate both the perfusion and functional status for AIS patients after reperfusion therapy. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:221-229.

A COACHS Nomogram to Predict the Probability of Three-Month Unfavorable Outcome after Acute Ischemic Stroke in Chinese Patients.

BACKGROUND: Accurate prognostication of unfavorable outcome made at the early onset of stroke is important to both the clinician and the patient management. This study was aimed to develop a nomogram based on the integration of parameters to predict the probability of 3-month unfavorable functional outcome in Chinese acute ischemic stroke patients. METHODS: We retrospectively collected patients who underwent acute ischemic stroke at Stroke Center of the Nanjing First Hospital (China) between May 2013 and May 2018. After exclusion, the study population includes 1,025 patients for nomogram development. The main outcome measure was 3-month unfavorable outcome (modified Rankin Scale > 2). Multivariable logistic regression analysis was used to develop the predicting model, and stepwise logistic regression with the Akaike information criterion was utilized to find best-fit nomogram model. We incorporated the creatinine, fast blood glucose, age, previous cerebral hemorrhage, previous valvular heart disease, and NHISS score (COACHS), and these factors were presented with a nomogram. We assessed the discriminative performance by using the area under curve (AUC) of receiver-operating characteristic (ROC) and calibration of risk prediction model by using the Hosmer-Lemeshow test. RESULTS: Multivariate analysis of the 1,025 patients for logistic regression helped identify the independent factors as National Institutes of Health Stroke Scale score on admission, age, previous valvular heart disease, fasting blood glucose, creatinine, and previous cerebral hemorrhage, which were included in the COACHS nomogram. The AUC-ROC of nomogram was 0.799. Calibration was good (p = 0.1376 for the Hosmer-Lemeshow test). CONCLUSIONS: The COACHS nomogram may be used to predict unfavorable outcome at 3 months after acute ischemic stroke in Chinese population. It may be also a reliable tool that is effective in its clinical utilization to risk-stratify acute stroke patients.

A NADE nomogram to predict the probability of 6-month unfavorable outcome in Chinese patients with ischemic stroke.

BACKGROUND: Early prediction of unfavorable outcome after ischemic stroke is of great significance to the clinical and therapeutic management. A nomogram is a better visual tool than earlier models and prognostic scores to predict clinical outcomes, which incorporates different factors to develop a graphic continuous scoring system and calculates accurately the risk probability of poor outcome entirely based on individual characteristics. However, to date, no nomogram models have been found to predict the probability of 6-month poor outcome after ischemic stroke. We aimed to develop and validate a nomogram for individualized prediction of the probability of 6-month unfavorable outcome in Chinese patients with ischemic stroke. METHODS: Based on the retrospective stroke registry, a single-center study which included 499 patients from May, 2013 to May, 2018 was conducted in Nanjing First Hospital (China) for ischemic stroke within 12 h of symptoms onset. The main outcome measure was 6-month unfavorable outcome (mRS > 2). To generate the nomogram, NIHSS score on admission, Age, previous Diabetes mellitus and crEatinine (NADE) were integrated into the model. We assessed the discriminative performance by using the area under the curve (AUC) of receiver-operating characteristic (ROC) and calibration of risk prediction model by using the Hosmer-Lemeshow test. RESULTS: A visual NADE nomogram was constructed that NIHSS score on admission (OR: 1.190, 95%CI: 1.125-1.258), age (OR: 1.068, 95%CI: 1.045-1.090), previous diabetes mellitus (OR: 1.995, 95%CI: 1.236-3.221) and creatinine (OR: 1.010, 95%CI: 1.002-1.018) were found to be significant predictors of 6-month unfavorable outcome after acute ischemic stroke in Chinese patients. The AUC-ROC of nomogram was 0.791. Calibration was good (p = 0.4982 for the Hosmer-Lemeshow test). CONCLUSION: The NADE is the first nomogram developed and validated in Chinese ischemic stroke patients to provide an individual, visual and precise prediction of the risk probability of 6-month unfavorable outcome.

External Validation of START nomogram to predict 3-Month unfavorable outcome in Chinese acute stroke patients.

BACKGROUND: Recently, the NIHSS STroke Scale score, Age, pre-stroke mRS score, onset-to-treatment Time (START nomogram) predicts 3-month functional outcome after intravenous thrombolysis in ischemic stroke patients. However, this model has not yet been an external validation. We aim to validate the performance of START nomogram. METHODS: Data were derived from the stroke center of the Nanjing First Hospital (China). Patients who lacked the necessary data to calculate the nomogram and missed 3-month modified Ranking scale scores were excluded. Modified Rankin Scale score more than 2 at 3-month was assessed as an unfavorable outcome. We used areas under the receiver operator characteristic curves (AUC-ROC) to quantify the prognostic value. Calibration was assessed by calibration plots and Hosmer-Lemeshow (HL) goodness of fit test. RESULT: The final cohort included 306 eligible patients. For 3-month unfavorable outcome, the AUC-ROC of the START nomogram was .766 (95%CI: .7013-.8304, P < .0001), suggesting good discrimination in the START nomogram. It also showed good calibration (HL goodness of fit test P = .1261) in the external validation sample. CONCLUSION: The START nomogram with good predictive performance is a reliable and simple clinical instrument to predict unfavorable outcome after acute stroke.

Emergent loading dose of antiplatelets for stenting after IV rt-PA in acute ischemic stroke: a feasibility study.

BACKGROUND: A loading dose of antiplatelets reduces in-stent thrombosis after stent implantation. However, whether it is safe in patients undergoing acute stenting after intravenous recombinant tissue plasminogen activator (rt-PA) is unclear. METHODS: A case series of acute ischemic stroke patients treated with intravenous rt-PA followed by emergent stenting were prospectively included in Jinling Hospital Stroke Unit. An emergent loading dose of antiplatelets (aspirin 300 mg and clopidogrel 300 mg) were administered to all patients through a nasogastric tube immediately before stenting. Clinical and angiographic outcomes were evaluated in these patients. RESULTS: A total of 12 patients were included. The median of NIHSS score on admission was 15 points (interquartile range 11-19). The median of time from stroke symptom onset to start IV rt-PA and stent placement was 172 min (interquartile range 123.75-189) and 311.5 min (interquartile range 285.5-349.5), respectively. All patients reached complete or partial recanalization (TICI ≥2a). One patient occurred hemorrhagic transformation at 24 h following the emergent loading dose of antiplatelets. A favorable outcome as defined by mRS ≤2 at 90 days was obtained in 58.3% (7/12) of all patients. CONCLUSION: Our finding preliminary suggested that an emergent loading dose of antiplatelets may be safe and feasible for acute stenting after IV rt-PA.

Severity assessment of intracranial large artery stenosis by pressure gradient measurements: A feasibility study.

BACKGROUND: Fractional flow reserve (FFR)-guided revascularization strategy is popular in coronary intervention. However, the feasibility of assessing stenotic severity in intracranial large arteries using pressure gradient measurements still remains unclear. METHODS: Between March 2013 and May 2014, 12 consecutive patients with intracranial large artery stenosis (including intracranial internal carotid artery, middle cerebral M1 segment, intracranial vertebral artery, and basilar artery) were enrolled in this study. The trans-stenotic pressure gradient was measured before and/or after percutaneous transluminal angioplasty and stenting (PTAS), and was then compared with percent diameter stenosis. A Pd /Pa cut-off of ≤0.70 was used to guide stenting of hemodynamically significant stenoses. The device-related and procedure-related serious adverse events and recurrent cerebral ischemic events were recorded. RESULTS: The target vessel could be reached in all cases. No technical complications occurred due to the specific study protocol. Excellent pressure signals were obtained in all patients. For seven patients who performed PTAS, the mean pre-procedural pressure gradient decreased from 59.0 ± 17.2 to 13.3 ± 13.6 mm Hg after the procedure (P < 0.01). Only one patient who refused stenting experienced a TIA event in the ipsilateral MCA territory. No recurrent ischemic event was observed in other patients. CONCLUSION: Mean trans-stenotic pressure gradients can be safely and easily measured with a 0.014-inch fluid-filled guide wire in intracranial large arteries. © 2016 Wiley Periodicals, Inc.

Predictors for vascular cognitive impairment in stroke patients.

BACKGROUND: Around two thirds stroke patients may suffer from vascular cognitive impairment (VCI). Our previous study has validated the NINDS-CSN harmonization standard for VCI diagnosis in Chinese. In this study, we aimed to investigate the predictors for VCI in Chinese post-stroke patients. METHODS: We compared epidemiological, clinical, and neuroimaging data (number, size and location of acute infarcts and lacunes, severities of white matter hyperintensities and brain atrophy) between stroke patients with and without VCI. Univariate and logistic regression analyses were utilized to determine VCI predictors. RESULTS: Fifty-six consecutive patients (age, 63.8 ± 8.3 years; female, 37.5%) were recruited at a mean interval of 7.1 months after stroke onset, and 31 (55.4%) patients were diagnosed with VCI based on a validated 60-min neuropsychological battery. VCI patients were older (p = 0.023), less educated (p = 0.001), more likely to be female (p < 0.001), had a recurrent stroke (p = 0.028), and described higher apathy (p = 0.022) and worse pre-stroke cognition (p = 0.048) than cognitively normal patients. Lower educational level (adjusted odds ratio [OR] 0.750, 95% confidence interval [CI], 0.573-0.981; p = 0.035), female sex (adjusted OR 8.288, 95% CI, 1.522-45.113; p = 0.014), recurrent stroke (adjusted OR 11.327, 95% CI, 1.335-96.130, p = 0.026), and global cortical atrophy (adjusted OR 5.730, 95% CI, 1.128-29.101, p = 0.035) were independently associated with VCI in post-stroke patients. CONCLUSIONS: Lower education, female sex, recurrent stroke and global cortical atrophy were associated with VCI in Chinese stroke patients.

Lower levels of plasma adiponectin and endothelial progenitor cells are associated with large artery atherosclerotic stroke.

BACKGROUND: Both adiponectin and endothelial progenitor cells (EPCs) have been proposed recently with anti-atherosclerosis effects. However, their impacts on vascular outcomes in patients with large artery atherosclerosis (LAA) are unclear. This study aimed to investigate the relationship between adiponectin, EPCs and stroke with a case-control design. METHODS: The study cohort included 127 patients (61.3 ± 11.0 years; 73.2% men) with LAA stroke and 58 control subjects (60.9 ± 9.2 years; 70.7% men) referred for adiponectin and EPCs levels testing. We collected demographic, clinical, angiographical features, and laboratory data. Influence of adiponectin and EPCs levels on cerebral atherosclerosis and LAA stroke was analyzed with regression models. RESULTS: The levels of adiponectin and EPCs in atherosclerotic stroke patients were significantly lower compared with matched controls (p < 0.05). Logistic regression analysis identified that reduced levels of adiponectin and EPCs were closely correlated with cerebral atherosclerosis and LAA stroke. The associations remained significant after adjustment for age, sex and other confounders. Additionally, partial correlation analysis revealed a significant positive association between adiponectin and three subpopulations of EPCs levels (CD34(+)CD133(+)CD309(+)cells: r = 0.510, p = 0.001; CD34(+) CD133(-)CD309(+)cells: r = 0.262, p = 0.004; CD34(-)CD133(+)CD309(+)cells: r = 0.348, p < 0.001). CONCLUSIONS: Adiponectin is positively correlated with EPCs levels, and both of them are independently associated with LAA stroke.

Neutrophil-to-Lymphocyte Ratio Predicts Length of Stay and Acute Hospital Cost in Patients with Acute Ischemic Stroke.

BACKGROUND: Although several risk factors for prolonged length of stay (LOS) and increased hospital cost have been identified, the association between LOS, hospital cost, and neutrophil-to-lymphocyte ratio (NLR) has not yet been investigated. We aimed to investigate the influence of NLR on LOS and hospital cost in patients with acute ischemic stroke. METHODS: Patients with acute ischemic stroke diagnosed within 24 hours of symptom onset were included. Univariate analysis and stepwise multiple regression analysis were used to identify independent predictors of LOS and hospital cost. RESULTS: A total of 346 patients were included in the final analysis. The median LOS was 11 days (range 8-13 days). The median acute hospital cost per patient was 19,030.6 RMB (U.S. $ 3065.8) (range 14,450.8 RMB-25,218.2 RMB). Neutrophil count to lymphocyte count (NLR) (P < .001), diabetes mellitus (P = .034), stroke subtype (P = .005), and initial stroke severity (P < .001) were significantly associated with prolonged LOS in the univariate analysis. NLR (P < .001), smoking (P = .04), stroke subtype (P < .001), initial stroke severity (P < .001), and LOS (P < .001) were significantly associated with increased hospital cost in the univariate analysis. Multivariate regression analysis showed that NLR was an independent predictor of both LOS and acute hospital cost. In addition, high NLR was significantly correlated with poor outcome at discharge, prolonged LOS, and increased hospital cost. CONCLUSIONS: NLR is significantly associated with LOS and acute hospital cost in patients presenting with acute ischemic stroke. It is a simple, inexpensive, and readily available biomarker and may serve as a clinically practical indicator for assessing the economic burden of stroke.

Validation of NINDS-CSN neuropsychological battery for vascular cognitive impairment in Chinese stroke patients.

BACKGROUND: The NINDS-Canadian Stroke Network (NINDS-CSN) recommended a neuropsychological battery of three protocols to diagnose vascular cognitive impairment (VCI), however, due to culture and language differences, the battery cannot be directly used in China. Validation of the battery in mandarin Chinese is lacking. Our study investigated the reliability and validity of the adapted Chinese versions of the battery in stroke patients with high probability of VCI. METHODS: Fifty mild stroke patients (median of National Institute of Health Stroke Scale [NIHSS] score, 2) and 50 stroke-free normal controls were recruited. All subjects' demographics, clinical history, and stroke severity were recorded. The NINDS-CSN neuropsychological protocols were adapted into the Chinese versions. External validity, defined as the ability of the protocol summary scores to differentiate stroke patients from controls, was determined using the area under the curve (AUC) of the receiver operating characteristics curve. We also evaluated internal consistency and intra-rater reliability. RESULTS: Stroke patients performed significantly poorer than controls on all three protocols (F statistics between 24.9 and 31.4, P < 0.001). External validity evaluated by AUCs was 0.88 (95% confidence interval [CI], 0.81-0.95), 0.88 (95% CI, 0.81-0.94), and 0.86 (95% CI, 0.79-0.94) for the 60-min, 30-min and 5-min protocols, respectively. Cronbach's alpha of the cognitive tests was 0.87 for all subjects. Intra-rater reliability was acceptable with intraclass correlation coefficients 0.90, 0.83 and 0.75 for the 60-min, 30-min and 5-min protocols, respectively. CONCLUSIONS: The adapted Chinese versions of three NINDS-CSN neuropsychological protocols were valid and reliable for assessing VCI in Chinese patients with mild stroke.

Telephone-based cognitive screening for stroke patients in China.

BACKGROUND: Valid telephone assessment for cognitive impairment is lacking in stroke settings. We investigated the feasibility and validity of the 5-minute National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) protocol and six-item screener (SIS) in stroke patients by telephone administration. METHODS: Patients were assessed with a comprehensive face-to-face neuropsychological assessment after three months of stroke onset, followed by the 5-minute NINDS-CSN protocol (30 points) and SIS (6 points) at least one month later. Administration time was recorded for the telephone tests. Validity of both tests was determined using the area under the receiver operating characteristics curve (AUC). RESULTS: Eighty-nine patients (age, 62.9 ± 8.6 years; male, 65.2%) received a face-to-face assessment and 80 completed telephone tests. The time required to administer the 5-minute NINDS-CSN protocol was 4.3 ± 1.0 minutes, and SIS 57.3 ± 17.7 seconds. Validity of detecting cognitive impairment as assessed by AUC was 0.86 (95% CI, 0.78-0.94) for 5-minute NINDS-CSN protocol, and 0.74 (95% CI, 0.63-0.85) for SIS. Sensitivity and specificity were optimal with the cut-off values of 23.5/24 for the 5-minute NINDS-CSN protocol, and 4/5 for SIS. CONCLUSIONS: Both the telephone-based 5-minute NINDS-CSN protocol and SIS were feasible and valid in screening cognitive impairment after stroke in China.

Whole Transcriptome Sequencing of Peripheral Blood Identifies the Alzheimer's Disease-Related circRNA-miRNA-lncRNA Pathway.

BACKGROUND: Previous studies on transcriptional profiles suggested dysregulation of multiple RNA species in Alzheimer's disease. However, despite recent investigations revealing various aspects of circular RNA (circRNA)-associated competing endogenous RNA (ceRNA) networks in Alzheimer's Disease (AD) pathogenesis, few genome-wide studies have explored circRNA-associated profiles in AD patients exhibiting varying degrees of cognitive loss. OBJECTIVE: To investigate the potential pathogenesis-related molecular biological changes in the various stages of AD progression. METHODS: Whole transcriptome sequencing was performed on the peripheral blood of 7 normal cognition (NC) subjects, 8 patients with mild cognitive impairment, 8 AD patients with mild dementia (miD), and 7 AD patients with moderate dementia (moD). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to predict the potential functions of the maternal genes of microRNAs (miRNAs), circRNAs and long non-coding RNAs (lncRNAs). The construction of ceRNA network was performed between the NC group and each diseased group based on the differently expressed RNAs. RESULTS: In total, 3568 mRNAs, 142 miRNAs, 990 lncRNAs, and 183 circRNAs were identified as significantly differentially expressed across the four groups. GO and KEGG enrichment analysis revealed the significant roles of GTPase activity and the MAPK signaling pathway in AD pathogenesis. A circRNA-miRNA-lncRNA ceRNA pathway, characterized by the downregulated hsa-miR-7-5p and upregulated hsa_circ_0001170, was identified based on the differentially expressed RNAs between the NC group and the moD group. CONCLUSION: The study suggests that circRNAs may be independent of messenger RNAs (mRNAs) in AD pathogenesis and holds promise as potential biomarkers for AD clinical manifestations and pathological changes.

[Prognostic effect of posterior cerebral artery laterality on middle cerebral artery occlusion].

OBJECTIVE: To explore the prognostic value of posterior cerebral artery (PCA) laterality in patients with symptomatic middle cerebral artery (MCA) occlusion on standard medical therapy. METHODS: Forty consecutive patients with first onset isolated atherosclerotic occlusion in M1 segment of MCA received medication from June 2009 to March 2013. All patients underwent magnetic resonance angiography (MRA) for assessment of PCA laterality. Clinical data and modified Rankin Scale (mRS) at 3 months were compared between PCA positive and negative patients. Retrospective analysis was performed on their clinical and imaging data. RESULTS: Among them, 20 patients (50%) showed PCA laterality on MRA and 32 patients (80%) completed a 3-month follow-up. No significant difference existed between PCA laterality positive and negative groups in a favorable outcome of mRS = 0-1 at 3 months (P = 0.433). CONCLUSION: The presence of PCA laterality showed no prognostic effect on patients with symptomatic MCA occlusion on standard medical therapy.

The Potential of Gut Microbiota in Prediction of Stroke-Associated Pneumonia.

BACKGROUND: Stroke-associated pneumonia (SAP) is a common stroke complication, and the changes in the gut microbiota composition may play a role. Our study aimed to evaluate the predictive ability of gut microbiota for SAP. METHODS: Acute ischemic stroke patients were prospectively enrolled and divided into two groups based on the presence or absence of SAP. The composition of gut microbiota was characterized by the 16S RNA Miseq sequencing. The gut microbiota that differed significantly between groups were incorporated into the conventional risk scores, the Acute Ischemic Stroke-Associated Pneumonia Score (AIS-APS), and the Age, Atrial fibrillation, Dysphagia, Sex, Stroke Severity Score (A2DS2). The predictive performances were assessed in terms of the area under the curve (AUC), the Net Reclassification Improvement (NRI), and the Integrated Discrimination Improvement (IDI) indices. RESULTS: A total of 135 patients were enrolled, of whom 43 had SAP (31%). The short-chain fatty acids (SCFAs)-producing bacteria, such as Bacteroides, Fusicatenibacter, and Butyricicoccus, were decreased in the SAP group. The integrated models showed better predictive ability for SAP (AUC = 0.813, NRI = 0.333, p = 0.052, IDI = 0.038, p = 0.018, for AIS-APS; AUC = 0.816, NRI = 0.575, p < 0.001, IDI = 0.043, p = 0.007, for A2DS2) in comparison to the differential genera (AUC = 0.699) and each predictive score (AUCAISAPS = 0.777; AUCA2DS2 = 0.777). CONCLUSIONS: The lower abundance of SCFAs-producing gut microbiota after acute ischemic stroke was associated with SAP and may play a role in SAP prediction.

Malnutrition and poststroke depression in patients with ischemic stroke.

BACKGROUND: Identifying high-risk patients based on modifiable clinical characteristics, such as malnutrition, is critical to intervening with these variables to reduce the risk of post-stroke depression (PSD). The aim of this study was to investigate the effect of nutritional status on the risk of incident PSD and the trajectory of PSD risk. METHODS: Consecutive patients with acute ischemic stroke were recruited in this observational cohort and followed up for 1 year. Multivariate logistic regressions and multilevel mixed-effects logistic regressions with random intercepts and slopes were used to investigate the effects of nutritional indexes [the Controlling Nutritional Status (CONUT) score, the Nutritional Risk Index (NRI), and the Prognostic Nutritional Index (PNI)] and body mass index (BMI) on the risk of incident PSD and the trajectory of PSD risk over the 12-month observation period. RESULTS: A total of 538 patients were included in the final analysis. Worsening CONUT [odds ratio (OR) = 1.36; confidence interval (CI): 1.15-1.61], NRI (OR = 0.91; CI: 0.87-0.96) and PNI (OR = 0.89; CI: 0.84-0.95) scores were significantly associated with an increased risk of incident PSD. Moderate and severe risk malnutrition statuses were associated with higher incidences of PSD regardless of the malnutrition index (CONUT, NRI or PNI). Additionally, PSD risk decreased over time with a significant two-way interaction between time and CONUT, NRI, and PNI, implying that patients with elevated exposure to malnutrition showed a slower decline in PSD risk. BMI had no significant effect on the occurrence and development of PSD. CONCLUSION: Malnutrition, but not BMI, was associated with a higher probability of incident PSD and was more likely to lead to a slower rate of decline in PSD risk.

Associations of Lipoprotein(a) Level with Cerebral Small Vessel Disease in Patients with Alzheimer's Disease.

BACKGROUND: This study aimed to examine the association of lipoprotein(a) [Lp(a)] level with the burden of cerebral small vessel disease (CSVD) in patients with Alzheimer's disease (AD). METHODS: Data from 111 consecutive patients with AD admitted to Nanjing First Hospital from 2015 to 2022 were retrospectively analyzed in this study. Serum Lp(a) concentrations were grouped into tertiles (T1-T3). Brain magnetic resonance imaging (MRI) was rated for the presence of CSVD, including enlarged perivascular spaces (EPVS), lacunes, white-matter lesions, and cerebral microbleeds (CMBs). The CSVD burden was calculated by summing the scores of each MRI marker at baseline. A binary or ordinal logistic regression model was used to estimate the relationship of serum Lp(a) levels with CSVD burden and each MRI marker. RESULTS: Patients with higher tertiles of Lp(a) levels were less likely to have any CSVD (T1, 94.6%; T2, 78.4%; T3, 66.2%; p = 0.013). Multivariable analysis found that Lp(a) levels were inversely associated with the presence of CSVD (T2 vs. T1: adjusted odds ratio [aOR] 0.132, 95% confidence interval [CI] 0.018-0.946, p = 0.044; T3 vs. T1: aOR 0.109, 95% CI 0.016-0.737, p = 0.023) and CSVD burden (T3 vs. T1: aOR 0.576, 95% CI 0.362-0.915, p = 0.019). The independent relationship between Lp(a) levels and individual CSVD features was significant for moderate-to-severe EPVS in the centrum semiovale (T2 vs. T1: aOR 0.059, 95% CI 0.006-0.542, p = 0.012; T3 vs. T1: aOR 0.029, 95% CI 0.003-0.273, p = 0.002) and CMBs (T3 vs. T1: aOR 0.144, 95% CI 0.029-0.716, p = 0.018). CONCLUSIONS: In this study, serum Lp(a) level was inversely associated with CSVD in AD patients.