Hang Jin

Objective: Minor strokes may be associated with early neurological deterioration (END) and disabilities. The objective was to investigate the role of serum glial fibrillary acidic protein (GFAP) levels in predicting END. Methods: Data originated from a multicenter cohort study conducted prospectively. ΔGFAP was calculated as the ratio of post‐thrombolysis GFAP at 24 h to baseline GFAP. Univariable and multivariable binary logistic regression analyses were performed to assess the association between ∆GFAP and END, and a nomogram was established to illustrate its predictive value. Results: END occurred in 20 (7.35%) of the 272 patients with minor stroke who underwent intravenous thrombolysis (IVT). Elevated ∆GFAP was independently associated with END (OR, 3.50; 95% CI, 1.67 to 7.31; p < 0.001), even after adjusting for confounders (adjusted OR, 4.64; 95% CI, 1.86 to 11.54; p < 0.001). Furthermore, a model combining ∆GFAP, age, and National Institutes of Health Stroke Scale (NIHSS) score at admission demonstrated a good predictive value for END (AUC = 0.77; 95% CI, 0.67 to 0.89). Interpretation: ∆GFAP is a strong, independent predictor of END in patients with minor strokes. Integrating ∆GFAP, age, and NIHSS score into a prognostic model results in a good discriminative ability for predicting END.

Following a stroke, a local inflammatory cascade is triggered, resulting in the systemic diminishment of immune function, known as stroke-induced immunosuppression. The association of stroke-induced immunosuppression with brain injury and stroke prognosis after intravenous thrombolysis remains unclear. In this cohort study, we prospectively enrolled 1023 patients across 16 centers. Lymphocyte counts and the neutrophil-to-lymphocyte ratio were used as indicators of the severity of stroke-induced immunosuppression. The primary outcomes were the 90-d functional outcome, assessed using the modified Rankin Scale, and the severity of brain injury, evaluated by serum biomarkers (glial fibrillary acidic protein, S100β, ubiquitin c-terminal hydrolase L1, and neuron-specific enolase). Key secondary outcomes included infarct volume, 24 h and 7 d National Institutes of Health Stroke Scale, early neurological deterioration, hemorrhagic transformation, and 3-month mortality. Our results demonstrated that stroke-induced immunosuppression was independently associated with functional outcomes at 3 months and the severity of brain injury. In addition, patients with severe stroke-induced immunosuppression had increased infarct volume, higher National Institutes of Health Stroke Scale scores, increased risk of hemorrhagic transformation, and higher 3-month mortality. These results suggest that stroke-induced immunosuppression is independently associated with brain injury and poor outcomes in patients with acute ischemic stroke undergoing intravenous thrombolysis.

BACKGROUND: Recent research has shown that neuroinflammation progresses rapidly within a few hours after stroke; however, the relationship between its progression and clinical outcomes remains unclear. Therefore, this study aimed to investigate the effect of neuroinflammation, measured by serum GFAP (glial fibrillary acidic protein), on patient outcomes, as well as the influence of baseline peripheral inflammation on the progression of neuroinflammation. METHODS: This prospective cohort study enrolled patients with acute ischemic stroke who received intravenous thrombolysis (IVT) between September 2016 and April 2023 across 16 centers in China. Serum GFAP levels were measured before (baseline, within 4.5 hours of onset) and at 24 hours after IVT. GFAP changes were determined by subtracting baseline levels from those measured 24 hours post-IVT. Outcome measures included final infarct volume during hospitalization, National Institutes of Health Stroke Scale scores at 24 hours and 7 days post-IVT, early neurological deterioration within 24 hours, delayed neurological deterioration within 7 days, and 3-month modified Rankin Scale scores. A modified Rankin Scale score of ≥2 was classified as an unfavorable outcome. Peripheral inflammation indicators were measured at baseline. Binary logistic and linear regressions were used as the main statistical methods. RESULTS: Overall, 743 patients were included. A significant increase in GFAP levels was observed, indicating progression of neuroinflammation. Regression analyses revealed that increased GFAP after IVT was independently associated with larger infarct volume (β, 30.965 [95% CI, 19.185–42.745]; P P P P <0.001). Furthermore, baseline peripheral inflammation, assessed using peripheral inflammation indicators, was significantly associated with elevated GFAP levels. CONCLUSIONS: The increase in GFAP levels over the first 24 hours after IVT is independently associated with clinical outcomes, with higher baseline peripheral inflammation correlating with greater GFAP elevation during that period.

Objective: Plasma fibrinogen is essential in thrombosis and fibrinolysis, yet its dynamic changes pre‐ and post‐intravenous thrombolysis (IVT) for predicting brain injury severity and prognosis in acute ischemic stroke (AIS) patients remain unclear. Aims: This study examined how fibrinogen trends before and after IVT correlate with brain injury severity and clinical outcomes in IVT‐treated patients. Methods: This multicenter study prospectively enrolled AIS patients treated with IVT at 16 hospitals and recorded their fibrinogen trends before and after thrombolysis. Levels of brain injury markers were measured to represent the extent of brain injury, including glial fibrillary acidic protein (GFAP), ubiquitin c‐terminal hydrolase L1 (UCH‐L1), S100β, and neuron‐specific enolase (NSE). Prognostic indicators included early neurological deterioration (END), hemorrhagic transformation, infarct volume, National Institutes of Health Stroke Scale (NIHSS) score at 7 days, 3‐month poor outcome (modified Rankin Scale [mRS] score > 1), and mortality. Results: A total of 827 patients were enrolled, with 207 exhibiting elevated fibrinogen levels 24 h after IVT. Patients with elevated fibrinogen levels exhibited significantly higher levels of brain injury markers (GFAP, UCH‐L1, S100β), larger infarct volumes, higher NIHSS scores at 7 days, and a higher incidence of END and poor outcomes compared to those with non‐elevated fibrinogen levels. Both univariate and multivariate analyses identified elevated fibrinogen levels after IVT as an independent predictor of severe brain injury, larger infarct volume, higher NIHSS score, occurrence of END, and poor outcomes. Interpretation: Elevated fibrinogen levels 24 h after IVT are independently associated with more severe brain injury and worse clinical outcomes in AIS patients.

The rising prevalence of ischemic stroke among younger individuals is concerning. Despite the significant benefits of intravenous thrombolytic therapy for young and middle-aged patients, the disease burden in this demographic is often overshadowed by that of older patient groups. This study aims to identify the risk factors for poor 3-month outcomes following intravenous thrombolysis in young and middle-aged patients with first-ever stroke and to develop a novel nomogram. This prospective study included patients aged 18 to 59 years with a first ischemic stroke from 16 hospitals. Patients from one of the hospitals were designated as the training cohort. General information and clinical data were compared between the favorable outcome (modified Rankin Scale [mRS] score < 2) and the poor outcome groups (mRS score ≥ 2). Logistic regression analysis was used to develop the nomogram. An additional 113 patients from the other 15 hospitals were recruited as the validation cohort. A total of 217 patients were enrolled in the training cohort, with 47% experiencing poor 3-month outcomes. Five variables were selected to construct the ANGWC (Age, NIHSS score, blood Glucose, White blood cell count, and total Cholesterol) nomogram. The AUC of the nomogram was 0.802 in the training cohort and 0.747 in the validation cohort. The Hosmer–Lemeshow goodness-of-fit test showed a P-value > 0.05, and calibration curve slopes were close to 1. Decision curve analysis indicated good clinical utility. The ANGWC nomogram provides a reliable prediction of poor 3-month outcomes after intravenous thrombolysis in young and middle-aged patients with first-ever stroke.

Changes in the deep medullary vein (DMV) are reported to be associated with cerebral small vessel disease (CSVD). While the mechanisms of this association are unclear, dynamic cerebral autoregulation (dCA) has been speculated to participate in this association. Thus, we aimed to verify the association between DMV changes and total CSVD burden and further investigate the effect of dCA function on this correlation. In this prospective study, 95 Asian patients aged ≥18 years were included in the final assessment. DMV scores and total CSVD burden were determined using magnetic resonance imaging sequences. Transfer function analysis was performed to analyze dCA function. Generalized linear regressions were used to assess the relationship between DMV changes and total CSVD burden as well as between DMV changes and dCA function. An interaction model was utilized to assess the effect of dCA function on the association between DMV changes and total CSVD burden. Generalized linear models showed a significant positive association between DMV changes and total CSVD burden (p = 0.039) and a significant negative association between DMV changes and dCA function (p = 0.018). The interaction model demonstrated a significant positive interaction of dCA impairment on the association between DMV changes and the total CSVD burden (p = 0.02). Thus, we came to the conclusion that changes in DMV were correlated independently with both CSVD and dCA impairment and furthermore, impaired dCA function play an interaction effect on the association between DMV changes and the total CSVD burden. Our results can help improve the understanding of the complex pathogenesis and progression of CSVD, thereby facilitating early intervention and treatment development.

After an ischemic stroke (IS) occurs, immune cells begin traveling to the brain and immune system from the gut and gastrointestinal tract, where most of them typically reside. Because the majority of the body’s macrophages and more than 70% of the total immune cell pool are typically found within the gut and gastrointestinal tract, inflammation and immune responses in the brain and immune organs require the mobilization of a large number of immune cells. The bidirectional communication pathway between the brain and gut is often referred to as the gut-brain axis. IS usually leads to intestinal motility disorders, dysbiosis of intestinal microbiota, and a leaky gut, which are often associated with poor prognosis in patients with IS. In recent years, several studies have suggested that intestinal inflammation and immune responses play key roles in the development of IS, and thus may become potential therapeutic targets that can drive new therapeutic strategies. However, research on gut inflammation and immune responses after stroke remains in its infancy. A better understanding of gut inflammation and immune responses after stroke may be important for developing effective therapies. This review discusses the immune-related mechanisms of the gut-brain axis after IS and compiles potential therapeutic targets to provide new ideas and strategies for the future effective treatment of IS.

Objective: Hyponatremia is the most common electrolyte disorder encountered in patients with neurological conditions, such as stroke. Studies have shown that it is associated with worse clinical outcomes and increased mortality in acute ischemic stroke (AIS). However, the role of hyponatremia has not been elucidated in patients with AIS who received intravenous thrombolysis (IVT) therapy. Therefore, this study aimed to investigate the effect of serum sodium levels on the clinical outcome and hemorrhagic transformation (HT) in patients with AIS who received thrombolytic therapy.Methods: Patients diagnosed with AIS who received IVT therapy between May 2015 and December 2020 were included in this study. All patients were screened for serum sodium levels immediately after hospital admission, before IVT therapy. The occurrence of HT was evaluated using computed tomography (CT) 24 ± 2 h after thrombolysis. Then, 3-month clinical outcomes were obtained by telephone calls or outpatient visits, and poor 3-month clinical outcomes were defined as modified Rankin Scale scores ≥3. The effects of serum sodium levels on the clinical outcome and HT were assessed using the multivariate logistic regression analysis.Results: Of the 963 included patients, 82 (8.5%) had hyponatremia, 157 (16.3%) developed HT, and 333 (34.6%) had poor 3-month outcomes. Of the 82 patients with hyponatremia, 21 (25.6%) developed HT, and 39 (47.6%) had poor 3-month outcomes. Patients with hyponatremia had a higher incidence of post-thrombolysis HT (25.6 vs. 15.4%, p = 0.017) and worse clinical outcome (47.6 vs. 33.4%, p = 0.01) than those with normal serum sodium levels. Patients had significantly lower serum sodium levels in those with HT [138.4 (136.4–140.3, IQR) vs. 139.0 (137.2–140.7, IQR) mmol/L, p = 0.019] and poor 3 month outcome [139.0 (137.2–140.7) vs. 138.4 (136.7–140.3) mmol/L, p = 0.005] than those without. After adjusting for major covariates, the multivariate logistic regression analysis revealed that lower serum sodium levels were independently associated with an increased risk of HT [odds ratio (OR) = 1.804; 95% CI: 1.048–3.105] and poor 3-month outcome (OR = 1.647; 95% CI: 1.012–2.679).Conclusion: Lower serum sodium level was an independent risk factor for post-thrombolysis HT and poor clinical outcome in patients with AIS who received thrombolytic therapy.