Quantitative imaging for predicting hematoma expansion in intracerebral hemorrhage: A multimodel comparison.

BACKGROUND: Several studies report that radiomics provides additional information for predicting hematoma expansion in intracerebral hemorrhage (ICH). However, the comparison of diagnostic performance of radiomics for predicting revised hematoma expansion (RHE) remains unclear. METHODS: The cohort comprised 312 consecutive patients with ICH. A total of 1106 radiomics features from seven categories were extracted using Python software. Support vector machines achieved the best performance in both the training and validation datasets. Clinical factors models were constructed to predict RHE. Receiver operating characteristic curve analysis was used to assess the abilities of non-contrast computed tomography (NCCT) signs, radiomics features, and combined models to predict RHE. RESULTS: We finally selected the top 21 features for predicting RHE. After univariate analysis, 4 clinical factors and 5 NCCT signs were selected for inclusion in the prediction models. In the training and validation dataset, radiomics features had a higher predictive value for RHE (AUC = 0.83) than a single NCCT sign and expansion-prone hematoma. The combined prediction model including radiomics features, clinical factors, and NCCT signs achieved higher predictive performances for RHE (AUC = 0.88) than other combined models. CONCLUSIONS: NCCT radiomics features have a good degree of discrimination for predicting RHE in ICH patients. Combined prediction models that include quantitative imaging significantly improve the prediction of RHE, which may assist in the risk stratification of ICH patients for anti-expansion treatments.

Prehospital Ultra-Early Neurological Deterioration in Intracerebral Hemorrhage: Definition, Prevalence, and Association with Outcomes.

INTRODUCTION: The objective of this study was to define prehospital ultra-early neurological deterioration (UND) and to investigate the association with functional outcomes in patients with intracerebral hemorrhage (ICH). METHODS: We conducted a prospective cohort study of consecutive acute ICH patients. The stroke severity at onset and hospital admission was assessed using the Chongqing Stroke Scale (CQSS), and prehospital UND was defined as a CQSS increase of ≥2 points between symptoms onset and admission. Early neurological deterioration (END) was defined as the increase of ≥4 points in NIHSS score within the first 24 h after admission. Poor outcome was defined as a modified Rankin Scale (mRS) of 4-6 at 3 months. RESULTS: Prehospital UND occurred in 29 of 169 patients (17.2%). Patients with prehospital UND had a median admission NIHSS score of 17.0 as opposed to those without prehospital UND with a median NIHSS score of 8.5. There were three patterns of neurological deterioration: prehospital UND only in 21 of 169 patients (12.4%), END but without prehospital UND in 20 of 169 patients (11.8%), and continuous neurological deterioration in both phases in 8 patients (4.7%). Prehospital UND was associated with worse 3-month outcomes (median mRS score, 4.0 vs. 2.0, p = 0.002). After adjusting for age, time from onset to admission, END, and systolic blood pressure, prehospital UND was an independent predictor of poor outcome (odds ratio [OR] 3.27, 95% confidence interval [CI] 1.26-8.48, p = 0.015). CONCLUSION: Prehospital UND occurs in approximately 1 in 7 patients between symptom onset and admission and is associated with poor functional outcome in patients with ICH. Further research is needed to investigate the prehospital UND in the prehospital phase in the triage of patients with ICH.

MicroRNA Transcriptomics Analysis Identifies Dysregulated Hedgehog Signaling Pathway in a Mouse Model of Acute Intracerebral Hemorrhage Exposed to Hyperglycemia.

OBJECTIVE: Hyperglycemia is often observed in the patients after acute stroke. This study aims to elucidate the potential effect and mechanism of hyperglycemia by screening microRNAs expression in intracerebral hemorrhage mice. METHODS: We employed the collagenase model of intracerebral hemorrhage. Twenty male C57BL/6 mice were used and randomly divided in normo- and hyperglycemic. The hyperglycemia was induced by intraperitoneally injection of 50% of Dextrose (8 mL/kg) 3 hours after intracerebral hemorrhage. The neurologic impairment was investigated by neurologic deficit scale. To study the specific mechanisms of hyperglycemia, microRNAs expression in perihematomal area was investigated by RNA sequencing. MicroRNAs expression in hyperglycemic intracerebral hemorrhage animals were compared normoglycemic mice. Functional annotation analysis was used to indicate potential pathological pathway, underlying observed effects. Finally, polymerase chain reaction validation was administered. RESULTS: Intraperitoneal injection of dextrose significantly increased blood glucose level. That was associated with aggravation of neurological deficits in hyperglycemic compared to normoglycemic animals. A total of 73 differentially expressed microRNAs were identified via transcriptomics analysis. Bioinformatics analyses showed that these microRNAs were significantly altered in several signaling pathways, of which the hedgehog signaling pathway was regarded as the most potential pathway associated with the effect of hyperglycemia on acute intracerebral hemorrhage. Furthermore, polymerase chain reaction results validated the correlation between microRNAs and hedgehog signaling pathway. CONCLUSIONS: MicroRNA elevated in hyperglycemia group may be involved in worsening the neurological function via inhibiting the hedgehog signaling, which provides a novel molecular physiological mechanism and lays the foundation for treatment of intracerebral hemorrhage.

Computed Tomography Imaging Predictors of Intracerebral Hemorrhage Expansion.

PURPOSE OF REVIEW: Hematoma expansion (HE) is strongly associated with poor clinical outcome and is a compelling target for improving outcome after intracerebral hemorrhage (ICH). Non-contrast computed tomography (NCCT) is widely used in clinical practice due to its faster acquisition at the presence of acute stroke. Recently, imaging markers on NCCT are increasingly used for predicting HE. We comprehensively review the current evidence on HE prediction using NCCT and provide a summary for assessment of these markers in future research studies. RECENT FINDINGS: Predictors of HE on NCCT have been described in reports of several studies. The proposed markers, including swirl sign, blend sign, black hole sign, island sign, satellite sign, and subarachnoid extension, were all significantly associated with HE and poor outcome in their small sample studies after ICH. In summary, the optimal management of ICH remains a therapeutic dilemma. Therefore, using NCCT markers to select patients at high risk of HE is urgently needed. These markers may allow rapid identification and provide potential targets for anti-HE treatments in patients with acute ICH.

Relationship Between Non-contrast Computed Tomography Imaging Markers and Perihemorrhagic Edema Growth in Intracerebral Hemorrhage.

OBJECTIVES: Perihemorrhagic edema (PHE) growth has been gradually considered as predictor for outcome of Intracerebral hemorrhage (ICH) patients. The aim of our study was to investigate correlation between non-contrast computed tomography (CT) markers and early PHE growth. METHODS: ICH patients between July 2011 and March 2017 were included in this retrospective analysis. ICH and PHE volumes were measured by using a validated semiautomatic volumetric algorithm. Nonparametric test was used for comparing PHE volume at different time points of non-contrast computed tomography (NCCT) imaging markers. Multivariable linear regression was constructed to study the relationship between NCCT imaging markers and PHE growth over 36 h. RESULTS: A total of 214 patients were included. Nonparametric test showed that PHE volume was significantly different between patients with and without NCCT imaging markers. (all p < 0.05) In multivariable linear regression analysis adjusted for ICH characteristics, blend sign (p = 0.011), black hole sign (p = 0.002), island sign (p < 0.001), and expansion-prone hematoma (p < 0.001) were correlated with PHE growth. Follow-up PHE volume within 36 h after baseline CT scan was associated with blend sign (p = 0.001), island sign (p < 0.001), and expansion-prone hematoma (p < 0.001). CONCLUSION: NCCT imaging markers of hematoma expansion are associated with PHE growth. This suggests that early PHE growth can be predicted using radiology markers on admission CT scan.

Hydrocephalus Growth: Definition, Prevalence, Association with Poor Outcome in Acute Intracerebral Hemorrhage.

BACKGROUND/OBJECTIVES: To propose a novel definition for hydrocephalus growth and to further describe the association between hydrocephalus growth and poor outcome among patients with intracerebral hemorrhage (ICH). METHODS: We analyzed consecutive patients who presented within 6 h after ICH ictus between July 2011 and June 2017. Follow-up CT scans were performed within 36 h after initial CT scans. The degree of hydrocephalus were evaluated by the hydrocephalus score of Diringer et al. The optimal increase of the hydrocephalus scores between initial and follow-up CT scan was estimated to define hydrocephalus growth. Poor long-term outcome was defined as a modified Rankin Scale of 4-6 at 3 months. Multivariate logistic regression analysis was performed to investigate the hydrocephalus growth for predicting 30-day mortality, 90-day mortality, and poor long-term outcome. RESULTS: A total of 321 patients with ICH were included in the study. Of 64 patients with hydrocephalus growth, 34 (53.1%) patients presented with both concurrent hematoma expansion and intraventricular hemorrhage (IVH) growth. After adjusting for potential confounding factors, hydrocephalus growth independently predicted 30-day mortality, 90-day mortality, and 90-day poor long-term outcome in multivariate logistic regression analysis. Hydrocephalus growth showed higher accuracy for predicting 30-day mortality, 90-day mortality, and poor long-term outcome than IVH growth or hematoma expansion, respectively. CONCLUSIONS: Hydrocephalus growth is defined by strongly predictive of short- or long-term mortality and poor outcome at 90 days, and might be a potential indicator for assisting clinicians for clinical decision-making.

Overlap of burnout-depression symptoms among Chinese neurology graduate students in a national cross-sectional study.

BACKGROUND: The overlap of burnout and depression is a phenomenon that can effectively reflect the psychological state of a group. However, whether burnout is a type of depression is still debated in current research. The high incidence of burnout and depressive symptoms among medical students indicates that it is urgent to provide appropriate health services for them. However, the proportion of burnout and depression in the overlapping symptoms experienced by medical students, and the characteristics of the relative influencing factors, remain unclear. Therefore, we addressed these issues for neurology graduate students in China. METHODS: Using data from a cross-sectional survey of Chinese neurology graduate students, a diagnostic model was established according to their burnout and/or depression symptoms. Burnout was assessed by using the Maslach Burnout Inventory. Depression symptoms were assessed with a two-item depression screening tool for primary care evaluation of mental disorders. Univariate analyses with chi-squared tests were conducted to assess associations between variables. Multinomial logistic regression models were used to analyze the effects of multiple factors on dependent variables. The factors included demographic information and three medical-study related problems. RESULTS: In total, 32.2% of surveyed students evidenced overlapping burnout and depression symptoms. Students with depressive symptoms tended to be included in the burnout students' category. In the regression model, being unmarried, having children, and career choice regret were related to students who had only burnout, while the students with overlapping symptoms were affected by more factors such as family income, the consideration of dropping out once. CONCLUSIONS: The symptoms and related factors of burnout and depression among Chinese neurology postgraduates have obvious overlap and show a significant trend. The occurrence of depressive symptoms among medical students is closely related to whether they are burned out. Students with only burnout were common, but students with only depressive symptoms were uncommon. Finally, burnout may be a pre-depression state.

Importance of lipid ratios for predicting intracranial atherosclerotic stenosis.

BACKGROUND: This study aims to investigate the association of lipid ratios with intracranial atherosclerotic stenosis (ICAS) in a Chinese population. METHODS: This cross-sectional study included 658 consecutive patients with ischemic stroke. Intracranial and extracranial arteries were evaluated for atherosclerotic stenosis using digital subtraction angiography or computed tomography angiography. Lipid ratios [total cholesterol (TC)/high-density lipoprotein-cholesterol (HDL-C), triglycerides (TG)/HDL-C, low-density lipoprotein-cholesterol (LDL-C)/HDL-C, non-high-density lipoprotein-cholesterol (non-HDL-C)/HDL-C, remnant cholesterol (RC)/HDL-C, apolipoprotein B (apo B)/apolipoprotein A-I (apo A-I), and apo B/HDL-C] were calculated. RESULTS: The TC/HDL-C, LDL-C/HDL-C, RC/HDL-C, non-HDL-C/HDL-C, apo B/HDL-C and apo B/apo A-I ratios (all P < 0.05) were significantly associated with ICAS but not with extracranial atherosclerotic stenosis after adjustment for confounding factors. Receiver operating characteristic (ROC) curves analysis revealed that the apo B/apo A-I ratio had the largest area under the ROC curve (AUC) among lipid levels alone and for lipid ratios (AUC = 0.588). Lipid ratios had higher AUC values than those for lipid levels alone for the identification of ICAS. CONCLUSION: The TC/HDL-C, LDL-C/HDL-C, RC/HDL-C, non-HDL-C/HDL-C apo B/HDL-C, and apo B/apo A-I ratios were significantly related to ICAS risk. Compared with the other variables tested, the apo B/apo A-I ratio appeared to be a better discriminator for identifying ICAS risk in stroke patients.

Intraventricular Hemorrhage Growth: Definition, Prevalence and Association with Hematoma Expansion and Prognosis.

BACKGROUND/OBJECTIVES: The objective of this study is to propose a definition of intraventricular hemorrhage (IVH) growth and to investigate whether IVH growth is associated with ICH expansion and functional outcome. METHODS: We performed a prospective observational study of ICH patients between July 2011 and March 2017 in a tertiary hospital. Patients were included if they had a baseline CT scan within 6 h after onset of symptoms and a follow-up CT within 36 h. IVH growth was defined as either any newly occurring intraventricular bleeding on follow-up CT scan in patients without baseline IVH or an increase in IVH volume ≥ 1 mL on follow-up CT scan in patients with initial IVH. Poor outcome was defined as modified Rankin Scale score of 3-6 at 90 days. The association between IVH growth and functional outcome was assessed by using multivariable logistic regression analysis. RESULTS: IVH growth was observed in 59 (19.5%) of 303 patients. Patients with IVH growth had larger baseline hematoma volume, higher NIHSS score and lower GCS score than those without. Of 44 patients who had concurrent IVH growth and hematoma growth, 41 (93.2%) had poor functional outcome at 3-month follow-up. IVH growth (adjusted OR 4.15, 95% CI 1.31-13.20; P = 0.016) was an independent predictor of poor functional outcome (mRS 3-6) at 3 months in multivariable analysis. CONCLUSION: IVH growth is not uncommon and independently predicts poor outcome in ICH patients. It may serve as a promising therapeutic target for intervention.

Expansion-Prone Hematoma: Defining a Population at High Risk of Hematoma Growth and Poor Outcome.

BACKGROUND: Noncontrast computed tomography (CT) markers are increasingly used for predicting hematoma expansion. The aim of our study was to investigate the predictive value of expansion-prone hematoma in predicting hematoma expansion and outcome in patients with intracerebral hemorrhage (ICH). METHODS: Between July 2011 and January 2017, ICH patients who underwent baseline CT scan within 6 h of symptoms onset and follow-up CT scan were recruited into the study. Expansion-prone hematoma was defined as the presence of one or more of the following imaging markers: blend sign, black hole sign, or island sign. The diagnostic performance of blend sign, black hole sign, island sign, and expansion-prone hematoma in predicting hematoma expansion was assessed. Predictors of hematoma growth and poor outcome were analyzed using multivariable logistical regression analysis. RESULTS: A total of 282 patients were included in our final analysis. Of 88 patients with early hematoma growth, 69 (78.4%) had expansion-prone hematoma. Expansion-prone hematoma had a higher sensitivity and accuracy for predicting hematoma expansion and poor outcome when compared with any single imaging marker. After adjustment for potential confounders, expansion-prone hematoma independently predicted hematoma expansion (OR 28.33; 95% CI 12.95-61.98) and poor outcome (OR 5.67; 95% CI 2.82-11.40) in multivariable logistic model. CONCLUSION: Expansion-prone hematoma seems to be a better predictor than any single noncontrast CT marker for predicting hematoma expansion and poor outcome. Considering the high risk of hematoma expansion in these patients, expansion-prone hematoma may be a potential therapeutic target for anti-expansion treatment in future clinical studies.

Black Hole Sign Predicts Poor Outcome in Patients with Intracerebral Hemorrhage.

BACKGROUND: In spontaneous intracerebral hemorrhage (ICH), black hole sign has been proposed as a promising imaging marker that predicts hematoma expansion in patients with ICH. The aim of our study was to investigate whether admission CT black hole sign predicts hematoma growth in patients with ICH. METHODS: From July 2011 till February 2016, patients with spontaneous ICH who underwent baseline CT scan within 6 h of symptoms onset and follow-up CT scan were recruited into the study. The presence of black hole sign on admission non-enhanced CT was independently assessed by 2 readers. The functional outcome was assessed using the modified Rankin Scale (mRS) at 90 days. Univariate and multivariable logistic regression analyses were performed to assess the association between the presence of the black hole sign and functional outcome. RESULTS: A total of 225 patients (67.6% male, mean age 60.3 years) were included in our study. Black hole sign was identified in 32 of 225 (14.2%) patients on admission CT scan. The multivariate logistic regression analysis demonstrated that age, intraventricular hemorrhage, baseline ICH volume, admission Glasgow Coma Scale score, and presence of black hole sign on baseline CT independently predict poor functional outcome at 90 days. There are significantly more patients with a poor functional outcome (defined as mRS ≥4) among patients with black hole sign than those without (84.4 vs. 32.1%, p < 0.001; OR 8.19, p = 0.001). CONCLUSIONS: The CT black hole sign independently predicts poor outcome in patients with ICH. Early identification of black hole sign is useful in prognostic stratification and may serve as a potential therapeutic target for anti-expansion clinical trials.

Comparison of Swirl Sign and Black Hole Sign in Predicting Early Hematoma Growth in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND Early hematoma growth is associated with poor outcome in patients with spontaneous intracerebral hemorrhage (ICH). The swirl sign (SS) and the black hole sign (BHS) are imaging markers in ICH patients. The aim of this study was to compare the predictive value of these 2 signs for early hematoma growth. MATERIAL AND METHODS ICH patients were screened for the appearance of the 2 signs within 6 h after onset of symptoms. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the 2 signs in predicting early hematoma growth were assessed. The accuracy of the 2 signs in predicting early hematoma growth was analyzed by receiver-operator analysis. RESULTS A total of 200 patients were enrolled in this study. BHS was found in 30 (15%) patients, and SS was found in 70 (35%) patients. Of the 71 patients with early hematoma growth, BHS was found on initial computed tomography scans in 24 (33.8%) and SS in 33 (46.5%). The sensitivity, specificity, PPV, and NPV of BHS for predicting early hematoma growth were 33.8%, 95.3%, 80.0%, and 72.0%, respectively. The sensitivity, specificity, PPV, and NPV of SS were 46.5%, 71.3%, 47.0%, and 71.0%, respectively. The area under the curve was 0.646 for BHS and 0.589 for SS (P=0.08). Multivariate logistic regression showed that presence of BHS is an independent predictor of early hematoma growth. CONCLUSIONS The Black hole sign seems to be good predictor for hematoma growth. The presence of swirl sign on admission CT does not independently predict hematoma growth in patients with ICH.

Defining the Optimal Midline Shift Threshold to Predict Poor Outcome in Patients with Supratentorial Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Midline shift (MLS) has been associated with unfavorable outcome in patients with intracerebral hemorrhage (ICH). However, the optimal criteria to define the MLS measurements that indicate future outcome in ICH patients are absent, and the quantitative threshold of MLS that differentiates favorable and poor clinical outcome should be further explored. METHODS: We enrolled patients with ICH who underwent admission computed tomography (CT) within 6 h after onset of symptoms. We assessed MLS at several locations, including the pineal gland, septum pellucidum, and cerebral falx. MLS(max) was defined as the maximum midline shift among these locations. Functional outcomes were assessed with the Modified Rankin Scale (mRS) at 3 months. We performed multivariate logistic regression analysis to investigate the MLS locations for predicting poor outcome. ROC curve analysis was used to establish whether MLS values were predictive of 90-day poor outcome. RESULTS: In 199 patients with ICH, 78 (39.2%) patients had poor functional outcome at 3-month follow-up. Pineal gland shift, septum pellucidum shift, cerebral falx shift, and MLS(max) all showed a significant difference between poor outcome and favorable outcome (p < 0.001). After adjustment for age, baseline Glasgow Coma Scale score, ICH location, time to initial CT, baseline ICH volume, and intraventricular hemorrhage, the MLS(max) was independently associated with poor outcome (p = 0.032). MLS(max) > 4 mm (our proposed optimal threshold) was more likely to have poorer outcomes than those without (p < 0.001). CONCLUSIONS: MLS(max) can be a good independent predictor of clinical outcome, and MLS(max) > 4 mm is an optimal threshold associated with poor outcome in patients with ICH.

Island Sign: An Imaging Predictor for Early Hematoma Expansion and Poor Outcome in Patients With Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: The aim of the study was to investigate the usefulness of the computed tomography (CT) island sign for predicting early hematoma growth and poor functional outcome. METHODS: We included patients with spontaneous intracerebral hemorrhage (ICH) who had undergone baseline CT within 6 hours after ICH symptom onset in our hospital between July 2011 and September 2016. Two readers independently assessed the presence of the island sign on the admission noncontrast CT scan. Multivariable logistic regression analysis was used to analyze the association between the presence of the island sign on noncontrast admission CT and early hematoma growth and functional outcome. RESULTS: A total of 252 patients who met the inclusion criteria were analyzed. Among them, 41 (16.3%) patients had the island sign on baseline noncontrast CT scans. In addition, the island sign was observed in 38 of 85 patients (44.7%) with hematoma growth. Multivariate logistic regression analysis demonstrated that the time to baseline CT scan, initial hematoma volume, and the presence of the island sign on baseline CT scan independently predicted early hematoma growth. The sensitivity of the island sign for predicting hematoma expansion was 44.7%, specificity 98.2%, positive predictive value 92.7%, and negative predictive value 77.7%. After adjusting for the patients' age, baseline Glasgow Coma Scale score, presence of intraventricular hemorrhage, presence of subarachnoid hemorrhage, admission systolic blood pressure, baseline ICH volume, and infratentorial location, the presence of the island sign (odds ratio, 3.51; 95% confidence interval, 1.26-9.81; P=0.017) remained an independent predictor of poor outcome in patients with ICH. CONCLUSIONS: The island sign is a reliable CT imaging marker that independently predicts hematoma expansion and poor outcome in patients with ICH. The noncontrast CT island sign may serve as a potential marker for therapeutic intervention.

Black Hole Sign: Novel Imaging Marker That Predicts Hematoma Growth in Patients With Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Early hematoma growth is a devastating neurological complication after intracerebral hemorrhage. We aim to report and evaluate the usefulness of computed tomography (CT) black hole sign in predicting hematoma growth in patients with intracerebral hemorrhage. METHODS: Patients with intracerebral hemorrhage were screened for the presence of CT black hole sign on admission head CT performed within 6 hours after onset of symptoms. The black hole sign was defined as hypoattenuatting area encapsulated within the hyperattenuating hematoma with a clearly defined border. The sensitivity, specificity, and positive and negative predictive values of CT black hole sign in predicting hematoma expansion were calculated. Logistic regression analyses were used to assess the presence of the black hole sign and early hematoma growth. RESULTS: A total of 206 patients were enrolled. Black hole sign was found in 30 (14.6%) of 206 patients on the baseline CT scan. The black hole sign was more common in patients with hematoma growth (31.9%) than those without hematoma growth (5.8%; P<0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of back hole sign in predicting early hematoma growth were 31.9%, 94.1%, 73.3%, and 73.2%, respectively. The time-to-admission CT scan, baseline hematoma volume, and the presence of black hole sign on admission CT independently predict hematoma growth in multivariate model. CONCLUSIONS: The CT black hole sign could be used as a simple and easy-to-use predictor for early hematoma growth in patients with intracerebral hemorrhage.

SERPINA3: A novel inflammatory biomarker associated with cerebral small vessel disease burden in ischemic stroke.

BACKGROUND AND OBJECTIVE: Inflammation has emerged as a prominent risk factor for cerebral small vessel disease (CSVD). However, the specific association between various inflammatory biomarkers and the development of CSVD remains unclear. Serine proteinase inhibitor A3 (SERPINA3), Matrix metalloproteinase-9 (MMP-9), Tissue inhibitor metalloproteinase-1 (TIMP-1), Monocyte Chemoattractant Protein-1 (MCP-1) are several inflammatory biomarkers that are potentially involved in the development of CSVD. In this present study, we aimed to investigate the relationship between candidate molecules and CSVD features. METHOD: The concentration of each biomarker was measured in 79 acute ischemic stroke patients admitted within 72 h after symptom onset. The associations between blood levels of inflammatory markers and CSVD score were investigated, as well as each CSVD feature, including white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces (EPVS). RESULTS: The mean age was 69.0 ± 11.8 years, and 65.8% of participants were male. Higher SERPINA3 level (>78.90 ng/mL) was significantly associated with larger WMH volume and higher scores on Fazekas's scale in all three models. Multiple regression analyses revealed the linear association between absolute WMH burden and SERPINA3 level, especially in model 3 (ß = 0.14; 95% confidence interval [CI], 0.04-0.24 ; p = 0.008 ). Restricted cubic spline regression demonstrated a dose-response relationship between SERPINA3 level and larger WMH volume (p nonlineariy = 0.0366 and 0.0378 in model 2 and mode 3, respectively). Using a receiving operating characteristic (ROC) curve, plasma SERPINA3 level of 64.15 ng/mL distinguished WMH >7.8 mL with the highest sensitivity and specificity (75.92% and 60%, respectively, area under curve [AUC] = 0.668, p = 0.0102). No statistically significant relationship has been found between other candidate biomarkers and CSVD features. CONCLUSION: In summary, among four inflammatory biomarkers that we investigated, SERPINA3 level at baseline was associated with WMH severity, which revealed a novel biomarker for CSVD and validated its relationship with inflammation and endothelial dysfunction.

Age-related changes after intracerebral hemorrhage: a comparative proteomics analysis of perihematomal tissue.

The risk factors and causes of intracerebral hemorrhage (ICH) and the degree of functional recovery after ICH are distinct between young and elderly patients. The increasing incidence of ICH in young adults has become a concern; however, research on the molecules and pathways involved ICH in subjects of different ages is lacking. In this study, tandem mass tag (TMT)-based proteomics was utilized to examine the protein expression profiles of perihematomal tissue from young and aged mice 24 h after collagenase-induced ICH. Among the 5,129 quantified proteins, ICH induced 108 and 143 differentially expressed proteins (DEPs) in young and aged mice, respectively; specifically, there were 54 common DEPs, 54 unique DEPs in young mice and 89 unique DEPs in aged mice. In contrast, aging altered the expression of 58 proteins in the brain, resulting in 39 upregulated DEPs and 19 downregulated DEPs. Bioinformatics analysis indicated that ICH activated different proteins in complement pathways, coagulation cascades, the acute phase response, and the iron homeostasis signaling pathway in mice of both age groups. Protein-protein interaction (PPI) analysis and ingenuity pathway analysis (IPA) demonstrated that the unique DEPs in the young and aged mice were related to lipid metabolism and carbohydrate metabolism, respectively. Deeper paired-comparison analysis demonstrated that apolipoprotein M exhibited the most significant change in expression as a result of both aging and ICH. These results help illustrate age-related protein expression changes in the acute phase of ICH.

Stroke depression: a concept with clinical applicability.

Stroke is a common neurological condition and among the leading causes of death and disability worldwide. Depression is both a risk factor for and complication of stroke, and the two conditions may have a complex reciprocal relationship over time. However, the secondary effects of depression on stroke are often overlooked, resulting in increased morbidity and mortality. In the previous concept of 'poststroke depression', stroke and depression were considered as two independent diseases. It often delays the diagnosis and treatment of patients. The concept 'stroke depression' proposed in this article will emphasise more the necessity of aggressive treatment of depression in the overall management of stroke, thus to reduce the incidence of stroke and in the meantime, improve the prognosis of stroke. Hopefully, it will lead us into a new era of acute stroke intervention.

Multi-time point metabolomics reveals key metabolic features from the ultra-early stage of intracerebral hemorrhage in mice.

Despite decades of intensive research, there are still very limited options for the effective treatment of intracerebral hemorrhage (ICH). Recently, mounting evidence has indicated that the ultra-early stage (<3 h), serving as the primary phase of ICH, plays a pivotal role and may even surpass other stages in terms of its significance. Therefore, uncovering the metabolic alterations induced by ICH in the ultra-early stage is of crucial importance. To investigate this, the collagenase ICH mouse model was employed in this study. ICH or sham-operated mice were euthanized at the ultra-early stage of 3 h and the acute stage of 24 h and 72 h after the operation. Then, the metabolic changes in the perihematomal tissues were detected by liquid chromatography coupled with tandem mass spectrometry. In total, alterations in the levels of 465 metabolites were detected. A total of 136 metabolites were significantly changed at 3 h. At 24 h and 72 h, the amounts were 132 and 126, respectively. Additionally, the key corresponding metabolic pathways for these time points were analyzed through KEGG. To gather additional information, quantitative real-time transcription polymerase chain reaction, enzyme-linked immunosorbent assay and Western blots were performed to validate the metabolic changes. Overall, ICH significantly alters important physiological functions such as cysteine metabolism, purine metabolism, synaptic alterations, the synaptic vesicle cycle, and the ATP-binding cassette transporter system. These might be the key pathologic mechanisms of the ultra-early stage induced by ICH.

Neutrophil percentage to albumin ratio is associated with stroke-associated pneumonia and poor outcome in patients with spontaneous intracerebral hemorrhage.

Background: The purpose of this study was to investigate the diagnostic performance of the neutrophil percentage-to-albumin ratio (NPAR) for predicting stroke-associated pneumonia (SAP) and functional outcome in patients with intracerebral hemorrhage (ICH). Methods: We analyzed our prospective database of consecutive ICH patients who were admitted to the First Affiliated Hospital of Chongqing Medical University from January 2016 to September 2021. We included subjects with a baseline computed tomography available and a complete NPAR count performed within 6h of onset. The patients' demographic and radiological characteristics were analyzed. Good outcome was defined as a modifed Rankin Scale score of 0-3 at 90 days. Poor outcome was defined as a modifed Rankin Scale score of 4-6 at 90 days. Multivariable logistic regression models were used to investigate the association between NPAR, SAP, and functional outcome. Receiver operating characteristic (ROC) curve analysis was conducted to identify the optimal cutoff of NPAR to discriminate between good and poor outcomes in ICH patients. Results: A total of 918 patients with ICH confirmed by non-contrast computed tomography were included. Of those, 316 (34.4%) had SAP, and 258 (28.1%) had poor outcomes. Multivariate regression analysis showed that higher NPAR on admission was an independent predictor of SAP (adjusted odds ratio: 2.45; 95% confidence interval, 1.56-3.84; P<0.001) and was associated with increased risk of poor outcome (adjusted odd ratio:1.72; 95% confidence interval, 1.03-2.90; P=0.040) in patients with ICH. In ROC analysis, an NPAR of 2 was identified as the optimal cutoff value to discriminate between good and poor functional outcomes. Conclusion: Higher NPAR is independently associated with SAP and poor functional outcome in patients with ICH. Our findings suggest that early prediction of SAP is feasible by using a simple biomarker NPAR.