Prediction of Neurological Deterioration After Intracerebral Hemorrhage: The SIGNALS Score.

Background Intracerebral hemorrhage is the most disabling and lethal form of stroke. We aimed to develop a novel clinical score for neurological deterioration during hospitalization after intracerebral hemorrhage. Methods and Results We analyzed data from the CHERRY (Chinese Cerebral Hemorrhage: Mechanism and Intervention) study. Two-thirds of eligible patients were randomly allocated into the training cohort (n=1027) and one-third into the validation cohort (n=515). Multivariable logistic regression was used to identify factors associated with neurological deterioration (an increase in National Institutes of Health Stroke Scale of ≥4 or death) within 15 days after symptom onset. A prediction score was developed based on regression coefficients derived from the logistic model. The site, size, gender, National Institutes of Health Stroke Scale, age, leukocyte, sugar (SIGNALS) score was developed as a sum of individual points (0-8) based on site (1 point for infratentorial location), size (3 points for >20 mL of supratentorial hematoma volume or 2 points for >10 mL of infratentorial hematoma volume), sex (1 point for male sex), National Institutes of Health Stroke Scale score (1 point for >10), age (1 point for ≥70 years), white blood cell (1 point for>9.0×109/L), and fasting blood glucose (1 point>7.0 mmol/L). The proportion of patients who suffered from neurological deterioration increased with higher SIGNALS score, showing good discrimination and good calibration in the training cohort (C statistic, 0.821; Hosmer-Lemeshow test, P=0.687) and in the validation cohort (C statistic, 0.848; Hosmer-Lemeshow test, P=0.592), respectively. Conclusions The SIGNALS score reliably predicts the risk of in-hospital neurological deterioration of patients with intracerebral hemorrhage.

Neuron derived fractalkine promotes microglia to absorb hematoma via CD163/HO-1 after intracerebral hemorrhage.

BACKGROUND: Hematoma leads to progressive neurological deficits and poor outcomes after intracerebral hemorrhage (ICH). Early clearance of hematoma is widely recognized as an essential treatment to limit the damage and improve the clinical prognosis. CD163, alias hemoglobin (Hb) scavenger receptor on microglia, plays a pivotal role in hematoma absorption, but CD163 on neurons permits Hb uptake and results in neurotoxicity. In this study, we focus on how to specially promote microglial but not neuronal CD163 mediated-Hb uptake and hematoma absorption. METHODS: RNA sequencing was used to explore the potential molecules involved in ICH progression, and hematoma was detected by magnetic resonance imaging (MRI). Western blot and immunofluorescence were used to evaluate the expression and location of fractalkine (FKN) after ICH. Erythrophagocytosis assay was performed to study the specific mechanism of action of FKN in hematoma clearance. Small interfering RNA (siRNA) transfection was used to explore the effect of peroxisome proliferator-activated receptor-γ (PPAR-γ) on hematoma absorption. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum FKN concentration in ICH patients. RESULTS: FKN was found to be significantly increased around the hematoma in a mouse model after ICH. With its unique receptor CX3CR1 in microglia, FKN significantly decreased the hematoma size and Hb content, and improved neurological deficits in vivo. Further, FKN could enhance erythrophagocytosis of microglia in vitro via the CD163/ hemeoxygenase-1 (HO-1) axis, while AZD8797 (a specific CX3CR1 inhibitor) reversed this effect. Moreover, PPAR-γ was found to mediate the increase in the CD163/HO-1 axis expression and erythrophagocytosis induced by FKN in microglia. Of note, a higher serum FKN level was found to be associated with better hematoma resolution in ICH patients. CONCLUSIONS: We systematically identified that FKN may be a potential therapeutic target to improve hematoma absorption and we shed light on ICH treatment.

Hematoma Expansion in Intracerebral Hemorrhage: An Update on Prediction and Treatment.

Intracerebral hemorrhage (ICH) is the most lethal type of stroke, but there is no specific treatment. After years of effort, neurologists have found that hematoma expansion (HE) is a vital predictor of poor prognosis in ICH patients, with a not uncommon incidence ranging widely from 13 to 38%. Herein, the progress of studies on HE after ICH in recent years is updated, and the topics of definition, prevalence, risk factors, prediction score models, mechanisms, treatment, and prospects of HE are covered in this review. The risk factors and prediction score models, including clinical, imaging, and laboratory characteristics, are elaborated in detail, but limited by sensitivity, specificity, and inconvenience to clinical practice. The management of HE is also discussed from bench work to bed practice. However, the upmost problem at present is that there is no treatment for HE proven to definitely improve clinical outcomes. Further studies are needed to identify more accurate predictors and effective treatment to reduce HE.