Association of Genetically Predicted Anxiety and Depression With Functional Outcome After Ischemic Stroke: A Mendelian Randomization Study.

BACKGROUND AND OBJECTIVES: Anxiety and depression have implications for ischemic stroke recovery. This study explored the association of genetically predicted anxiety and depression with functional outcome after ischemic stroke using Mendelian randomization (MR) approach. METHODS: Independent genetic variants associated with anxiety and depression at genome-wide significance level (p < 5 × 10-8) were obtained from large-scale genome-wide association studies (Nmax = 1,306,354). Genetic results of poststroke outcome were obtained from Genetics of Ischemic Stroke Functional Outcome meta-analysis (N = 6,021). Three months after ischemic stroke event, the functional outcome was appraised with the modified Rankin Scale (mRS) score, and a mRS >2 was defined as worse functional outcome. Odds ratios (ORs) and 95% CIs are reported for the association of genetically predicted anxiety and depression with functional outcome after ischemic stroke. The inverse-variance weighted method was adopted to pool estimates. Alternative MR methods such as the weighted median and MR using the Robust Adjusted Profile Score were used as sensitivity analyses. The intercept of MR-Egger regression was also adopted to assess pleiotropy. The heterogeneity among variants was assessed by I2 and Q statistics. RESULTS: Genetic liability to depression was associated with worse functional outcome after stroke (mRS 3-6, OR 2.30; 95% CI 1.18-4.49, p = 0.015). Sensitivity analyses produced consistent results. The bidirectional MR analysis indicates that poststroke outcome did not influence liability to depression (OR 1.01, 95% CI 0.99-1.03; p = 0.436). By comparison, genetic liability to anxiety was not related with poststroke outcome (OR 1.03; 95% CI 0.71-1.50; p = 0.869). Analyses in models without adjustment for stroke severity also indicated that genetic liability to depression was related with poor functional outcome after ischemic stroke (OR 2.54; 95% CI 1.41-4.58; p = 0.002). No evidence of heterogeneity or directional pleiotropy was observed (p > 0.05). DISCUSSION: Our MR study provides evidence to support detrimental effects of depression on ischemic stroke functional outcome. Future studies are warranted to explore whether clinical intervention on depression can ameliorate functional outcome after ischemic stroke.

Association between ischaemic stroke aetiology and leptomeningeal collateral status: a retrospective cohort study.

INTRODUCTION: There is limited understanding of the pathomechanistic relationship between leptomeningeal collateral formation and ischaemic stroke aetiology. We aimed to assess the association of leptomeningeal collateral status and ischaemic stroke aetiology, using the widely recognised "Trial of Org 10172 in Acute Stroke Treatment" (TOAST) classification categorising strokes into five distinct aetiologies. METHODS: Retrospective study of consecutively admitted adult ischaemic stroke patients at a Swiss stroke centre. Leptomeningeal collateral status was assessed on admission with single-phase CT-angiographies using a validated 4-point score. Patients were categorised into large-artery atherosclerosis (LAA), cardioembolic (CE), small-vessel disease (SVD) and cryptogenic (CG) according to the TOAST classification. We performed ordinal and binary (poor [collaterals filling ≤50% of the occluded territory] vs good [collaterals filling >50% of the occluded territory] collateralisation) logistic regression to evaluate the impact of TOAST aetiology on collateral status. RESULTS: Among 191 patients, LAA patients had better collateral status compared to non-LAA aetiology (LAA: 2 vs CE: 2 vs SVD: 3 vs CG: 2, pLAA vs non-LAA = 0.04). In weighted multivariate logistic regression, LAA and SVD independently predicted better collateral status (binary models [adjusted odds ratio; aOR]: LAA: 3.72 [1.21-11.44] and SVD: 4.19 [1.21-14.52]; ordinal models [adjusted common odds ratio; acOR]: LAA: 2.26 [95% CI: 1.23-4.15] and SVD: 1.94 [1.03-3.66]), while CE predicted worse collateral status (binary models [aOR]: CE: 0.17 [0.07-0.41]; ordinal models [acOR]: CE: 0.24 [0.11-0.51]). CONCLUSION: The aetiology of ischaemic stroke is associated with leptomeningeal collateral status on single-phase CT-angiography, with LAA and SVD predicting better and CE predicting worse collateral status.

Serum Levels and Clinical Significance of NSE, BDNF and CNTF in Patients with Cancer-associated Ischemic Stroke Complicated with Post-stroke Depression.

BACKGROUND: The incidence of post-stroke depression (PSD) may be higher in patients with cancer-associated ischemic stroke (CAIS). The pathogenesis of PSD is mainly related to the emotional injury of stroke and the inability of neurons to effectively repair. This study aims to explore the clinical significance of serum neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) expression levels in CAIS patients. METHODS: Clinical data of 106 patients with CAIS admitted to Jinhua Guangfu Oncology Hospital from January 2012 to December 2022 were retrospectively analyzed. Serum levels of NSE, BDNF and CNTF were measured in all patients after admission. Depression screening was performed by Hamilton Depression Scale-17 (HAMD-17) three months after intravenous thrombolysis. Patients with HAMD-17 score >7 were included in the PSD group (n = 44), and patients with HAMD-17 score ≤7 were included in the non-PSD group (n = 62). The general data and serum levels of NSE, BDNF and CNTF were compared between the two groups. According to HAMD-17 scores, patients in PSD group were further divided into mild depression group (8-16 points), moderate depression group (17-23 points) and severe depression group (≥24 points), and the serum levels of NSE, BDNF and CNTF were compared among the three groups. Pearson's correlation test was used to analyze the correlation between HAMD-17 scores and serum NSE, BDNF and CNTF levels in PSD patients. Logistic regression model was used to determine the influencing factors of PSD in CAIS patients. Receiver operating characteristic (ROC) curve was plotted to analyze the predictive efficacy of serum NSE, BDNF, CNTF and their combination on PSD. RESULTS: Among 106 CAIS patients, the incidence of PSD was 41.51% (44 cases), including 19 patients with mild PSD (43.18%), 14 patients with moderate PSD (31.82%), and 11 patients with severe PSD (25.00%). There were statistically significant differences in negative life events and complications after thrombolytic therapy between PSD and non-PSD patients (p < 0.05). The serum NSE level in PSD group was significantly higher than that in non-PSD group, and the serum BDNF and CNTF levels were notably lower than those in non-PSD group (all p < 0.001). The serum levels of NSE, BDNF and CNTF in patients with different severity of PSD were statistically significant (all p < 0.001). HAMD-17 scores in PSD patients were positively correlated with serum NSE levels (r = 0.676, p < 0.001) and negatively correlated with serum BDNF and CNTF levels (r = -0.661, p < 0.001; r = -0.401, p = 0.007, respectively). By binary logistic regression analysis, the levels of serum NSE, BDNF and CNTF were independent influencing factors for PSD in CAIS patients, among which NSE was a risk factor (odds ratio (OR) >1, p < 0.05), BDNF and CNTF were protective factors (OR <1, p < 0.05). CONCLUSION: This study reveals for the first time that the levels of serum NSE, BDNF and CNTF are closely related to the occurrence and development of PSD in CAIS patients. In clinical CAIS patients with abnormal changes in the above indicators, in addition to anti-tumor treatment and improvement of neurological deficit symptoms, attention should also be paid to the symptoms of psychological disorders.

Association and temporal sequence of pneumonia and gastrointestinal bleeding after acute ischemic stroke.

BACKGROUND: Stroke-associated pneumonia (SAP) and gastrointestinal bleeding (GIB) are common medical complications after stroke. The previous study suggested a strong association between SAP and GIB after stroke. However, little is known about the time sequence of SAP and GIB. In the present study, we aimed to verify the association and clarify the temporal sequence of SAP and GIB after ischemic stroke. METHODS: Patients with ischemic stroke from in-hospital Medical Complication after Acute Stroke study were analyzed. Data on occurrences of SAP and GIB during hospitalization and the intervals from stroke onset to diagnosis of SAP and GIB were collected. Multiple logistic regression was used to evaluate the association between SAP and GIB. Kruskal-Wallis test was used to compare the time intervals from stroke onset to diagnosis of SAP and GIB. RESULTS: A total of 1129 patients with ischemic stroke were included. The median length of hospitalization was 14 days. Overall, 86 patients (7.6%; 95% CI, 6.1-9.2%) developed SAP and 47 patients (4.3%; 95% CI, 3.0-5.3%) developed GIB during hospitalization. After adjusting potential confounders, SAP was significantly associated with the development of GIB after ischemic stroke (OR = 5.13; 95% CI, 2.02-13.00; P < 0.001). The median time from stroke onset to diagnosis of SAP was shorter than that of GIB after ischemic stroke (4 days vs. 5 days; P = 0.039). CONCLUSIONS: SAP was associated with GIB after ischemic stroke, and the onset time of SAP was earlier than that of GIB. It is imperative to take precautions to prevent GIB in stroke patients with SAP.

Association between Mobility of Residual Left Atrial Thrombus and Stroke Severity in Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: The differences in the characteristics of ischemic stroke associated with a mobile versus nonmobile residual left atrial thrombus (LAT) are unclear. We investigated whether the mobility of an LAT detected by transthoracic echocardiography is associated with the clinical features of stroke. METHODS: This study included 20 consecutive patients with nonvalvular atrial fibrillation who were admitted to our hospital for treatment of acute ischemic stroke and then found to have an LAT on transthoracic echocardiography. The patients were divided into two groups: those with a mobile LAT (Group M) and those with a nonmobile LAT (Group N). The clinical, neuroradiological, and echocardiographic variables were assessed. RESULTS: The LAT was mobile in 11 patients (Group M) and nonmobile in nine patients (Group N). The median National Institutes of Health Stroke Scale score on admission was higher in Group M than N (17 vs. 7, respectively; p=0.196). Four patients in Group M and one in Group N developed in-hospital stroke recurrence (36% vs. 11%, respectively; p=0.319). The prevalence of large vessel occlusion (15 events in Group M and 10 events in Group N, including in-hospital recurrent events) was significantly higher in Group M than N (73% vs. 30%, respectively; p=0.049), which seemed to lead to poorer functional outcomes in Group M than N (ratio of modified Rankin scale score of 0-2 at discharge: 18% vs. 44%, respectively; p=0.336). CONCLUSIONS: The mobility of LAT may affect stroke severity in patients with nonvalvular atrial fibrillation.

Association of Acute Incidental Cerebral Microinfarcts With Subsequent Ischemic Stroke in Patients With Cancer: A Population-Based Study.

BACKGROUND AND OBJECTIVES: Incidental diffuse-weighted imaging (DWI)-positive subcortical and cortical lesions, or acute incidental cerebral microinfarcts (CMIs), are a common type of brain ischemia, which can be detected on magnetic resonance DWI for approximately 2 weeks after occurrence. Acute incidental CMI was found to be more common in patients with cancer. Whether acute incidental CMI predicts future ischemic stroke is still unknown. We aimed to examine the association between acute incidental CMI in patients with cancer and subsequent ischemic stroke or transient ischemic attack (TIA). METHODS: This is a retrospective cohort study. We used Clalit Health Services records, representing over half of the Israeli population, to identify adults with lung, breast, pancreatic, or colon cancer who underwent brain MRI between January 2014 and April 2020. We included patients who underwent scan between 1 year before cancer diagnosis and 1 year after diagnosis. Primary outcome was ischemic stroke or TIA using International Classification of Diseases, Ninth Revision codes. Secondary outcomes were intracranial hemorrhage (ICH) and mortality. Records were followed from first MRI until primary outcome, death, or end of follow-up (January 2023). Cox proportional hazards models were used to calculate hazard ratio (HR) for patients with and without acute incidental CMI, as a time-dependent covariate. RESULTS: The study cohort included 1,618 patients with cancer, among whom, 59 (3.6%) had acute incidental CMI on at least 1 brain MRI. The median (interquartile range) time from acute incidental CMI to stroke or TIA was 26 days (14-84). On multivariable analysis, patients with acute incidental CMI had a higher stroke or TIA risk (HR 2.97, 95% CI 1.08-8.18, p = 0.035) compared with their non-CMI counterparts. Acute incidental CMIs were also associated with mortality after multivariable analysis (HR 2.76, 95% CI 2.06-3.71, p < 0.001); no association with ICH was found. DISCUSSION: Acute incidental CMI on brain MRI in patients with active cancer is associated with an increased risk of near-future ischemic stroke or TIA and mortality. This finding might suggest that randomly detected acute incidental CMI in patients with cancer may guide primary cerebrovascular risk prevention and etiologic workup.

A retrospective study on the prevalence and risk factors of neurogenic lower urinary tract dysfunction for acute ischemic stroke in China: A case-control study.

PURPOSE: This study identified risk factors for neurogenic lower urinary tract dysfunction (NLUTD) in patients with acute ischemic stroke (AIS) through multidimensional analysis of the medical records of patients, aiming to reduce the incidence of NLUTD, improve prognosis, and facilitate rehabilitation. MATERIALS AND METHODS: In this case-control study, patients with AIS were recruited from two tertiary general hospitals in Shenzhen, China, from March 2021 to October 2023. Patients were divided into NLUTD and non-NLUTD groups based on the presence and absence of NLUTD, respectively. Comparative analysis was performed using the Mann-Whitney U and chi-square tests, with significant variables being included in logistic regression analysis. RESULTS: Of the 652 participants enrolled in this study, 119 participants (18.3%) developed NLUTD. Bivariate analysis showed that 39 of 54 screened factors exhibited a significant correlation (p<0.05) with the incidence of NLUTD after AIS. Significant variables identified through logistic regression analysis included Glasgow coma scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) scores, anemia, aphasia, pneumonia, brainstem involvement, multiple lesions, urine clarity (CLA), random venous blood glucose (GLU) and hemoglobin (HGB) levels, and white blood cell (WBC) count. CONCLUSIONS: A total of 11 risk factors for NLUTD were identified in this study. This finding provides valuable guidance for reducing the incidence of NLUTD after AIS and improving the quality of life of patients.

A Rare Multinuclear Lesion Secondary to Multifactorial Ischemic Stroke: A Case Report on Eight-and-a-Half Syndrome.

Internuclear ophthalmoparesis (INO) is a horizontal eye movement disorder that is associated with a lesion at the medial longitudinal fasciculus (MLF). One-and-a-half syndrome occurs when the lesion involves the MLF and the ipsilateral abducens nuclei or the paramedian pontine reticular formation (PPRF) in the dorsomedial tegmentum of the pons. When the lesion is large enough, the fascicles of the facial nerve (CNVII) can also be involved, resulting in an ipsilateral facial nerve palsy. In combination with one-and-a-half syndrome, this condition becomes eightand- a- half syndrome (EHS). Here, we describe a unique case of EHS in a 72-year-old male with multiple ischemic stroke risk factors who presented with INO, conjugate gaze palsy, ipsilateral facial palsy, and a transient contralateral hemiparesis. Recognizing this pattern of neurologic deficits improves localization of the lesion, prevents misdiagnosis of Bell's Palsy, and expedites proper treatment.

Assessment of the impact of resting heart rate on the risk of major adverse cardiovascular events after ischemic stroke: a retrospective observational study.

BACKGROUND: Although elevated heart rate is a risk factor for cardiovascular morbidity and mortality in healthy people, the association between resting heart rate and major cardiovascular risk in patients after acute ischemic stroke remains debated. This study evaluated the association between heart rate and major adverse cardiovascular events after ischemic stroke. METHODS: We conducted a retrospective cohort study analyzing data from the Chang Gung Research Database for 21,655 patients with recent ischemic stroke enrolled between January 1, 2010, and September 30, 2018. Initial in-hospital heart rates were averaged and categorized into 10-beats per minute (bpm) increments. The primary outcome was the composite of hospitalization for recurrent ischemic stroke, myocardial infarction, or all-cause mortality. Secondary outcomes were hospitalization for recurrent ischemic stroke, myocardial infarction, and heart failure. Hazard ratios and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, using the heart rate < 60 bpm subgroup as the reference. RESULTS: After a median follow-up of 3.2 years, the adjusted hazard ratios for the primary outcome were 1.13 (95% CI: 1.01 to 1.26) for heart rate 60-69 bpm, 1.35 (95% CI: 1.22 to 1.50) for heart rate 70-79 bpm, 1.64 (95% CI: 1.47 to 1.83) for heart rate 80-89 bpm, and 2.08 (95% CI: 1.85 to 2.34) for heart rate ≥ 90 bpm compared with the reference group. Heart rate ≥ 70 bpm was associated with increased risk of all secondary outcomes compared with the reference group except heart failure.  CONCLUSIONS: Heart rate is a simple measurement with important prognostic implications. In patients with ischemic stroke, initial in-hospital heart rate was associated with major adverse cardiovascular events.

Proximal and distant expression of growth differentiation factor 15 (GDF15) correlate with neurological deficit following experimental ischemic stroke.

BACKGROUND AND PURPOSE: Growth differentiation factor 15 (GDF15) has emerged as a promising biomarker in cerebro-cardiovascular disease, particularly in acute and chronic inflammatory stress situations. However, understanding the origins, targets and functions of GDF15 in clinical situations, such as ischemic stroke, remains a complex challenge. This study aims to assess the sources of GDF15 production following an experimental ischemic stroke. METHODS: Adult male Wistar rats underwent cerebral embolization through microspheres injection into the left or right internal carotid artery. Two hours post-surgery, GDF15 expression was analyzed in the brain, blood, lungs, liver and heart using quantitative RT-PCR and Western blotting. RESULTS: Stroke model induced large cerebral infarcts accompanied by severe neurological deficits. GDF15 gene expression exhibited a substantial increase in the ipsilateral cortex and cerebellum, with a lesser extent in the contralateral cortex. Regarding GDF15 protein expression, proGDF15 levels were elevated in the 3 aforementioned organs mentioned and the heart. However, the mature form of GDF15 was exclusively present and increased in the heart. Finally, the expression of GDF15 expression was correlated with the neurological deficit score. CONCLUSIONS: Our findings suggest that both the GDF15 gene and pro-protein are expressed in the ischemic brain after a stroke, while only its mature form is expressed remotely in in the heart. The impact of increased GDF15 in the heart following a stroke remains to be established. This is particularly relevant in understanding its relationships with poor neurological outcomes, determining whether it may contribute to stroke-induced cardiac dysfunction.

Feasibility and efficacy of virtual reality rehabilitation compared with conventional physiotherapy for upper extremity impairment due to ischaemic stroke: protocol for a randomised controlled trial.

INTRODUCTION: Approximately half of all stroke survivors have persistent upper extremity functional impairment, leading to reduced self-care, independence and quality of life. High-intensity, task-oriented virtual reality rehabilitation improves motor recovery. However, its clinical efficacy over standard rehabilitation remains uncertain. This study aims to evaluate the feasibility and efficacy of a virtual reality-based comprehensive rehabilitation gaming system (VR-cRGS) in stroke survivors with upper extremity impairment and to characterise the structural and functional plasticity of the affected regions in the brain due to the proposed rehabilitation. METHODS AND ANALYSIS: This study is a multicentric, open-label, randomised controlled trial with an intention-to-treat analysis. A total of 162 patients will be enrolled in two academic institutes in India that specialise in stroke care. Patients with a first-ever ischaemic stroke (18-70 years and 1-6 months of stroke onset) with upper extremity impairment with 1 and 1+ grades of spasticity as per the modified Ashworth Scale and 3, 4 or 5 stages on Brunnstrom recovery staging will be enrolled. They will be randomised (1:1) into two treatment groups to receive 12 weeks of training either on VR-cRGS or on conventional physiotherapy. The primary feasibility outcome is compliance with the treatment. The primary efficacy outcome is the functional recovery of the upper extremity assessed by the Fugl-Meyer Assessment-Upper Extremity and Wolf Motor Function Test. The secondary outcomes are the Barthel Index and the 36-item Short-Form Health Survey. Multimodal brain imaging will be done in all enrolled patients at baseline and post-treatment to evaluate the structural and functional connectivity changes. The outcome measures will be analysed using paired t-tests or non-parametric tests. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Ethics Review Board of the Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India (SCT/IEC/1415/AUGUST-2019) and the National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India (NIMHANS/IEC (BS and NS DIV.)/32nd Meeting/21). All participants will sign an informed consent form prior to participation. The study results will be disseminated through scholarly publication. TRIAL REGISTRATION NUMBER: CTRI/2021/11/038339.

Peripheral immunity is associated with cognitive impairment after acute minor ischemic stroke and transient ischemic attack.

Immunoinflammation is associated with the development of post-stroke cognitive impairment (PSCI), however, peripheral immunity has not been fully explored. We aimed to investigate the association between PSCI and peripheral immune indicators, including neutrophil, lymphocyte, and mononuclear percentages and counts; the systemic immune inflammation index; platelet-to-lymphocyte ratio; neutrophil-to-lymphocyte ratio (NLR); and lymphocyte-to-monocyte ratio. A total of 224 patients with acute minor ischemic stroke or transient ischemic attack with 6-12 months of follow-up were included. PSCI was defined as a Montreal Cognitive Assessment score < 22 during the follow-up period. We performed logistic regression, subgroup analyses based on age and sex, and further established predictive models. We found that increased innate immunity indicators (neutrophils, neutrophil percentage) increased the risk of PSCI, whereas increased adaptive immunity indicator (lymphocytes) were protective against PSCI, especially in patients aged 50-65 years. Neutrophil percentage and NLR improved the predictive efficacy of the models that included demographic, clinical, and imaging information, with the area under the curve increased from 0.765 to 0.804 and 0.803 (P = 0.042 and 0.049, respectively). We conducted a comprehensive analysis of peripheral immunity in PSCI, providing a novel perspective on the early detection, etiology, and treatment of PSCI.

Association of Body Water Balance, Nutritional Risk, and Sarcopenia with Outcome in Patients with Acute Ischemic Stroke: A Single-Center Prospective Study.

In the present study, we examined the inter-relationships between body water balance, nutritional risk, sarcopenia, and outcome after acute ischemic stroke (AIS) in patients who were living independently. We defined abnormal body water balance as overhydration, with an extracellular fluid/total body water ratio > 0.390. A geriatric nutritional risk index (GNRI) < 98 was considered low GNRI. Sarcopenia was defined according to the 2019 Asian Working Group for sarcopenia criteria. Poor outcome was defined as a modified Rankin scale (mRS) score ≥ 3 at discharge. Among 111 eligible patients (40 females, median age: 77 years), 43 had a poor prognosis, 31 exhibited overhydration, 25 had low GNRI, and 44 experienced sarcopenia. Patients with poor outcomes had significantly higher National Institutes of Health Stroke Scale (NIHSS) scores, which were significantly more common with overhydration, low GNRI, and sarcopenia (p < 0.001 for all). Concomitant overhydration, low GNRI, and sarcopenia were associated with poorer outcomes. In multivariate analysis, overhydration [odds ratio (OR) 5.504, 95% confidence interval (CI) 1.717-17.648; p = 0.004], age (OR 1.062, 95%CI 1.010-1.117; p = 0.020), and NIHSS score (OR 1.790, 95%CI 1.307-2.451; p < 0.001) were independent prognostic factors for poor outcome. The results indicated that the combination of overhydration, low GNRI, and sarcopenia predict poor outcomes following AIS. Overhydration was particularly associated with poor outcomes.

Association between fibrinogen levels and stroke-associated pneumonia in acute ischemic stroke patients.

PURPOSE: Prior research had indicated a relationship between fibrinogen and stroke-associated pneumonia (SAP), yet the nature of this relationship had not been thoroughly investigated. Therefore, this study was designed to elucidate the prognostic value of fibrinogen levels in forecasting the occurrence of SAP among patients with acute ischemic stroke (AIS). PATIENTS AND METHODS: In this retrospective cross-sectional analysis, we included 1092 patients who had experienced AIS and were admitted to our facility within 72 h of the onset of their symptoms. Based on the SAP diagnostic criteria, patients were classified into two groups: SAP and non-SAP. The correlation between serum fibrinogen concentration and SAP was examined using univariate analysis. Curve fitting and multivariable logistic regression model were utilized for statistical evaluation. RESULTS: Out of the ischemic stroke patients included in the study, SAP was identified in 112 (10.26%) patients. A direct correlation was observed between fibrinogen levels and the incidence of SAP. An increase in fibrinogen levels corresponded with a heightened incidence of SAP. Multivariable logistic regression revealed a significant positive association between fibrinogen levels and SAP incidence (OR = 1.53, 95% confidence interval [CI]: 1.18, 1.99)). CONCLUSION: A linear relationship between serum fibrinogen levels and the incidence of SAP in ischemic stroke patients was shown. The serum fibrinogen levels were positively and linearly correlated to SAP risk.

Beta-Hydroxybutyrate Mitigates Sensorimotor and Cognitive Impairments in a Photothrombosis-Induced Ischemic Stroke in Mice.

The consequences of stroke include cognitive deficits and sensorimotor disturbances, which are largely related to mitochondrial impairments in the brain. In this work, we have shown that the mimetic of the ketogenic diet beta-hydroxybutyrate (ßHB) can improve neurological brain function in stroke. At 3 weeks after photothrombotic stroke, mice receiving ßHB with drinking water before and after surgery recovered faster in terms of sensorimotor functions assessed by the string test and static rods and cognitive functions assessed by the Morris water maze. At the same time, the ßHB-treated mice had lower expression of some markers of astrocyte activation and inflammation (Gfap, Il-1b, Tnf). We hypothesize that long-term administration of ßHB promotes the activation of the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway, which leads to increased expression of antioxidant genes targeting mitochondria and genes involved in signaling pathways necessary for the maintenance of synaptic plasticity. ßHB partially maintained mitochondrial DNA (mtDNA) integrity during the first days after photothrombosis. However, in the following three weeks, the number of mtDNA damages increased in all experimental groups, which coincided with a decrease in Ogg1 expression, which plays an important role in mtDNA repair. Thus, we can assume that ßHB is not only an important metabolite that provides additional energy to brain tissue during recovery from stroke under conditions of mitochondrial damage but also an important signaling molecule that supports neuronal plasticity and reduces neuroinflammation.

Increased plasma levels of N-terminal pro-B-type natriuretic peptide as biomarker for the diagnosis of cardioembolic ischaemic stroke.

BACKGROUND: Despite comprehensive study, the aetiology of stroke is not identified in 35% of cases. AIMS: We conducted a study to assess the diagnostic capacity of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the identification of ischaemic stroke of cardioembolic origin. The secondary purpose of the study was to evaluate the prognostic value of NT-proBNP for predicting 90-day all-cause mortality. METHODS: We designed a prospective observational study including patients hospitalised due to stroke between March 2019 and March 2020. Blood samples were collected on admission to the emergency department and serum NT-proBNP levels were determined. Statistical analysis was performed using a bivariate logistic regression model and receiver operating characteristic (ROC) and Kaplan-Meier curves. Statistical significance was established at p<.05. RESULTS: The study included 207 patients with first ischaemic stroke. Plasma NT-proBNP levels were significantly higher (p<.001) in the cardioembolic stroke group (2069pg/mL±488.5). ROC curves showed that NT-proBNP>499pg/mL was the optimum value for diagnosing cardioembolic ischaemic stroke (sensitivity, 82%; specificity, 80%). Moreover, plasma NT-proBNP levels>499pg/mL were independently associated with cardioembolic stroke (OR: 9.881; p=.001). Finally, NT-proBNP>1500pg/mL was useful for predicting 90-day mortality (sensitivity, 70%; specificity, 93%). CONCLUSIONS: NT-proBNP was independently associated with cardioembolic stroke and should be quantified in blood tests within 24h of stroke onset. High plasma levels (>499pg/mL) may indicate an underlying cardioembolic cause, which should be further studied, while NT-proBNP >1500pg/mL was associated with increased 90-day mortality.

[Brain-derived neurotrophic factor in the acute and early recovery period of ischemic stroke: the role of nocturnal hypoxemia]. / Mozgovoi neirotroficheskii faktor pri ishemicheskom insul'te v ostrom i rannem vosstanovitel'nom periodakh: rol' nochnoi gipoksemii.

OBJECTIVE: To study the relationship between brain-derived neurotrophic factor (BDNF) and the severity of nocturnal hypoxemia in patients in the acute and early recovery period of ischemic stroke (IS). MATERIAL AND METHODS: We enrolled 44 patients (27 men, 17 women), aged 18-85 years, in the acute phase of IS. At 3-month follow-up, 35 people were examined (21 men and 14 women). In the acute period, in addition to routine diagnostic procedures, respiratory monitoring was carried out, and the serum level of BDNF was measured by enzyme-linked immunosorbent assay. BDNF level was also evaluated at 3-month follow-up visit. Neurological status and its dynamics in the acute period of stroke were assessed as part of the clinical routine according to the National Institutes of Health Stroke Scale (NIHSS) at admission and discharge. RESULTS: We found a direct correlation between the duration of hypoxemia with SpO2 less than 90% (r=0.327, p=0.035) and less than 85% (r=0.461, p=0.003) and BDNF level in the acute phase of IS. BDNF level in the acute period of IS was negatively correlated with the minimum saturation value (r=-0.328, p=0.034). There was a direct relationship between BDNF level in the early recovery period and the duration of hypoxemia with SpO2 less than 85% (r=-0.389, p=0.028). A regression model showed that BDNF level was associated with the minimum SpO2 level. No significant associations were found with indicators of sleep-disordered breathing severity, such as the apnea-hypopnea index and the oxygen desaturation index. CONCLUSION: The severity of nocturnal hypoxemia is associated with the increase in BDNF levels both in the acute and recovery periods of IS, regardless of the presence of concomitant breathing disorders during sleep.

Neuroimaging and Neurological Outcomes in Perinatal Arterial Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Prediction of outcomes in perinatal arterial ischemic stroke (PAIS) is challenging. We performed a systematic review and meta-analysis to determine whether infarct characteristics can predict outcomes in PAIS. METHODS: A systematic search was conducted using five databases in January 2023. Studies were included if the sample included children with neonatal or presumed PAIS; if infarct size, location, or laterality was indicated; and if at least one motor, cognitive, or language outcome was reported. The level of evidence and risk of bias were evaluated using the Risk of Bias in Non-Randomized Studies of Interventions tool. Meta-analyses were conducted comparing infarct size or location with neurological outcomes when at least three studies could be analyzed. RESULTS: Eighteen full-text articles were included in a systematic review with nine included in meta-analysis. Meta-analyses revealed that small strokes were associated with a lower risk of cerebral palsy/hemiplegia compared with large strokes (risk ratio [RR] = 0.263, P = 0.001) and a lower risk of epilepsy (RR = 0.182, P < 0.001). Middle cerebral artery (MCA) infarcts were not associated with a significantly different risk of cerebral palsy/hemiplegia compared with non-MCA strokes (RR = 1.220, P = 0.337). Bilateral infarcts were associated with a 48% risk of cerebral palsy/hemiplegia, a 26% risk of epilepsy, and a 58% risk of cognitive impairment. CONCLUSIONS: Larger stroke size was associated with worse outcomes across multiple domains. Widely heterogeneous reporting of infarct characteristics and outcomes limits the comparison of studies and the analysis of outcomes. More consistent reporting of infarct characteristics and outcomes will be important to advance research in this field.