Risk Of Early Neurological Deterioration Research Articles

A Randomized Controlled Trial of Tenecteplase Versus Standard of Care for Minor Ischemic Stroke with Proven Occlusion (TEMPO-2): Rational and design of a multicenter, randomized open-label clinical trial.

Almost half of acute ischemic stroke patients present with mild symptoms and there are large practice variations in their treatment globally. Individuals with an intracranial occlusion who present with minor stroke are at an increased risk of early neurological deterioration and poor outcomes. Individual patient data meta-analysis in the subgroup of patients with minor deficits showed benefit of alteplase in improving outcomes; however, this benefit has not been seen with intravenous alteplase in published randomized trials. TEMPO-2 (A Randomized Controlled Trial of Tenecteplase Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion) is a prospective, open label with blinded outcome assessment, randomized controlled trial, designed to test the superiority of intravenous tenecteplase (0.25 mg/kg) over nonthrombolytic standard of care, with an estimated sample size of 1274 patients. Adult patients presenting with acute ischemic stroke with the National Institutes of Health Stroke Scale (NIHSS) ⩽ 5 and visible arterial occlusion or perfusion deficit within 12 h of onset are randomized to receive either tenecteplase (0.25 mg/kg) or standard of care. The primary outcome is return to baseline neurological functioning, measured by the modified Rankin scale (mRS) at 90 days. Safety outcomes include death and symptomatic hemorrhage (intra or extra-cranial). Other secondary outcomes include mRS 0-1, mRS 0-2, ordinal shift analysis of the mRS, partial, and full recanalization on follow-up computed tomography angiogram. Results of this trial will aid in determining whether there is benefit of using tenecteplase (0.25 mg/kg) in treating patients presenting with minor stroke who are at high risk of developing poor outcomes due to presence of an intracranial occlusion. Data will be available upon reasonable request.

Correlations of 2 Novel Inflammation Indexes With the Risk for Early Neurological Deterioration in Acute Ischemic Stroke Patients After Intravenous Thrombolytic Therapy.

Elevation of the systemic immune inflammation (SII) index and system inflammation response index (SIRI) is known to be associated with higher risk of stroke and all-cause death. However, no study has reported their correlation with early neurological deterioration (END) following recombinant tissue-type plasminogen activator (IV-rtPA) in acute ischemic stroke patients. The aim of this study was to explore the correlation of SII and SIRI with the risk of END after IV-rtPA. Included in this study were 466 consecutive patients treated with IV-rtPA. SII and SIRI were calculated according to blood cell counts before IV-rtPA. Patients were divided into 3 groups based on trisectional quantiles according to SII and SIRI values. The risk of END was assessed by multivariate regression. The overall discriminative ability of SII and SIRI in predicting END was assessed by receiver operating characteristic curve analysis. Of the 466 included patients, 62 (13.3%) were identified as having END. Compared with the first tertile of SII, multivariable regression analysis demonstrated that patients were more likely to have END (odds ratio 2.54; 95% CI: 1.23-5.23) and poor outcome at 90 days (odds ratio 2.02; 95% CI: 1.06-3.86) in third tertile after adjustment for potential confounders. In addition, a cutoff value of 591.63 for SII was detected in predicting post-thrombolysis END with a sensitivity of 58.1% and a specificity of 64.6% (area under the curve 0.61; 95% CI: 0.54-0.69). Higher SII but not SIRI may prove to be a predictor for high risk of END and a poor functional outcome at 90 days after IV-rtPA.

Effects of Tirofiban on Neurological Deterioration in Patients With Acute Ischemic Stroke

Evidence supports using antiplatelet therapy in patients with acute ischemic stroke. However, neurological deterioration remains common under the currently recommended antiplatelet regimen, leading to poor clinical outcomes. To determine whether intravenous tirofiban administered within 24 hours of stroke onset prevents early neurological deterioration in patients with acute noncardioembolic stroke compared with oral aspirin. This investigator-initiated, multicenter, open-label, randomized clinical trial with blinded end-point assessment was conducted at 10 comprehensive stroke centers in China between September 2020 and March 2023. Eligible patients were aged 18 to 80 years with acute noncardioembolic stroke within 24 hours of onset and had a National Institutes of Health Stroke Scale (NIHSS) score of 4 to 20. Patients were assigned randomly (1:1) to receive intravenous tirofiban or oral aspirin for 72 hours using a central, web-based, computer-generated randomization schedule; all patients then received oral aspirin. The primary efficacy outcome was early neurological deterioration (increase in NIHSS score ≥4 points) within 72 hours after randomization. The primary safety outcome was symptomatic intracerebral hemorrhage within 72 hours after randomization. A total of 425 patients were included in the intravenous tirofiban (n = 213) or oral aspirin (n = 212) groups. Median (IQR) age was 64.0 years (56.0-71.0); 124 patients (29.2%) were female, and 301 (70.8%) were male. Early neurological deterioration occurred in 9 patients (4.2%) in the tirofiban group and 28 patients (13.2%) in the aspirin group (adjusted relative risk, 0.32; 95% CI, 0.16-0.65; P = .002). No patients in the tirofiban group experienced intracerebral hemorrhage. At 90-day follow-up, 3 patients (1.3%) in the tirofiban group and 3 (1.5%) in the aspirin group died (adjusted RR, 1.15; 95% CI, 0.27-8.54; P = .63), and the median (IQR) modified Rankin scale scores were 1.0 (0-1.25) and 1.0 (0-2), respectively (adjusted odds ratio, 1.28; 95% CI, 0.90-1.83; P = .17). In patients with noncardioembolic stroke who were seen within 24 hours of symptom onset, tirofiban decreased the risk of early neurological deterioration but did not increase the risk of symptomatic intracerebral hemorrhage or systematic bleeding. ClinicalTrials.gov Identifier: NCT04491695.

Higher baseline serum bilirubin levels are associated with increased risk of early neurological deterioration in women with acute ischemic stroke.

Early neurological deterioration (END) occurs in up to one-third of patients with acute ischemic stroke (AIS) and associated with poor outcome. The role of serum bilirubin in END remains controversial. This study aims to investigate the association of total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) with END. This study was a cross-sectional retrospective study with 344 AIS patients enrolled. We retrospectively reviewed consecutive AIS patients with END through a medical record retrieval system and enrolled patients as control randomly from the AIS patients without END at the same period. The bilirubin levels were compared between the END group and No END group. The correlations of bilirubin with END were assessed according to the bilirubin tertiles on the cohort of different genders. In women, as the bilirubin level increased, the occurrence of END showed an increasing trend. The linear association was significant based on the tertiles of all bilirubin types (TBIL p = 0.003; DBIL p = 0.025; IBIL p = 0.025), while in men no similar trend was observed. After adjustment for confounders, higher TBIL (p for trend 0.009) and DBIL (p for trend 0.033) levels were associated with increased risk of END in women. The adjusted OR for T3 relative to T1 was 5.240 (95% CI 1.496-18.347) in TBIL and 3.549 (95% CI 1.089-11.566) in DBIL. Multivariate logistic regression showed that DBIL was independently associated with END in women (OR 1.717, 95% CI 1.106-2.666). The study also found that DBIL was superior to TBIL and IBIL in prediction of END occurrence in women, with greater predictive value. There were gender differences in the relationship between bilirubin and END, and DBIL level was positively associated with END occurrence in women, not in men. DBIL had greater incremental predictive value for END than TBIL and IBIL.

Evaluation of routine laboratory markers as short-term outcome indicators in patients with acute ischemic stroke

Abstract Introduction: Stroke is a disease with high mortality and morbidity. Currently, there are no specific laboratory markers that can replace or improve clinical and radiological diagnosis and prognosis. We evaluated the role of C-reactive protein (CRP), fibrinogen and D-dimer in predicting short-term outcomes in acute ischemic stroke. Methods: We included 118 acute ischemic stroke patients, admitted within 24 h of onset, mean age 72.73±10.08 years. The severity of the stroke was assessed by the National Institutes of Health Stroke Scale (NIHSS), and for poor outcome (PO) we accepted a severe functional deficit at the end of the hospital stay with NIHSS ≥15, and for good outcome (GO) – NIHSS ≤ 14. In all patients, we monitored the dynamics of CRP, fibrinogen and D-dimer and evaluated their predictive value regarding to the PO and GO of the stroke. Results: D-dimer had the strongest poor predictive value at admission (p<0.001). Six hours after admission, CRP, D-dimer or both were higher in PO patients (p=0.046, p=0.022 and p=0.006, respectively). At the 24.h, only CRP could be used to predict PO (p<0.001). Elevated CRP, D-dimer or both have been determined as strong indicators of PO with 72 hours of admission (p<0.001, p=0.032 and p=0.001, respectively). Fibrinogen levels were higher 72 hours after admission without a significant relationship with the NIHSS. Conclusion: Changes in routine biomarkers CRP and D-dimer, but not fibrinogen, can predict short-term stroke prognosis and may be associated with the risk of early neurological deterioration or death during hospital stay.

Variants in 3p24.3 predicts the risk of early neurological deterioration in large artery atherosclerotic stroke

The rate of early neurological deterioration (END) differs in different subtypes of ischaemic stroke. Previous studies showed PLCL2 gene is a novel susceptibility locus for the occurrence of atherosclerosis and thrombotic events. The objective of this research is to examine the efficacy that PLCL2 may have on the risk of END in large artery atherosclerotic (LAA) stroke. Tagged single nucleotide polymorphisms (SNPs) were identified by a strategy of fine-mapping. The genotyping of the selected SNPs was performed by SNPscan. The impact of PLCL2 on indicating the susceptibility of END in LAA patients was evaluated by binary logistic regression. The SNP–SNP interactions of PLCL2 for END was assessed by generalized multifactor dimensionality reduction (GMDR). A total of 1527 LAA stroke patients were recruited, 582 patients (38 %) experienced END. Compared to participants without END, participants experienced END were much older (P = 0.018), more likely to suffer pre-existing diabetes mellitus (P = 0.036), higher frequent in active tobacco users (P = 0.022) and had much higher median NIHSS on admission (P < 0.001). Rs4685423 was identified to be a predictor to the risk of END: the frequency of END in AA genotype patients is lower than that in AC or CC genotype patients (multivariate-adjusted, OR 0.63; 95 % CI 0.49–0.80; P < 0.001). The SNP-SNP interactions analysis indicates rs4685423 has the greatest impacton the risk of END for LAA patients. The time from admission diagnosis to END onset in AA genotype patients is much later than that in CA or CC genotype patients (log-rank, P = 0.005). In summary, the PLCL2 rs4685423 SNP is probably associated with the END risk in LAA stroke patients.

Analysis of the diagnostic informativity of non-contrast computed tomography markers of intracerebral hemorrhage expansion in assessment of the individual risk of early neurological deterioration in patients with hemorrhagic hemispheric stroke

The aim of the study was to evaluate the diagnostic informativity of non-contrast computed tomography (NCCT) markers of intracerebral hemorrhage (ICH) expansion in assessment of the individual risk of early neurological deterioration (END) in patients with hemorrhagic hemispheric stroke (HHS). Materials and methods. A prospective, cohort study was conducted involving 333 patients in the acute period of hypertensive spontaneous supratentorial ICH on the background of conservative therapy. The level of neurological deficit was assessed using the Full Outline of Unresponsiveness (FOUR) coma scale and the National Institute of Health Stroke Scale (NIHSS). The computed tomography of the brain was used to verify the ICH volume, the midline shift (MS), the secondary intraventricular hemorrhage volume (IVHV) and NCCT markers of intracerebral hemorrhage expansion. As a combined clinical endpoint, END was considered (decrease of the FOUR scale score ≥2 or/and increase of the NIHSS score ≥4 or/and lethal outcome within 48 hours of hospitalization). Results. Early neurological deterioration was registered in 112 patients. On the basis of a comparative analysis, it was established that the specific weight of END was significantly higher in subcohorts of patients with individual NCCT markers of intracerebral hemorrhage expansion, than it was in subcohorts of patients without corresponding NCCT signs (p ˂ 0.0001). It was established that the following NCCT markers of ICH expansion are the most sensitive predictors of END: hypodensity, swirl sign and irregular shape (sensitivity &gt;90.0 %). The most specific NCCT markers were island sign, black hole sign, blend sign, satellite sign and heterogeneous density (specificity &gt;87.0 %). In accordance with the multiple logistic regression analysis, hypodensity (OR (95 % CI) = 13.56 (4.54–40.49), p &lt; 0.0001) and island sign (OR (95 % CI) = 5.94 (2.05–17.16), p = 0.0010) are independently associated with the risk of END. A highly sensitive multi-prediction logistic regression model was elaborated in order to predict END in patients with HHS which takes into account the most informative NCCT markers of ICH expansion (hypodensity, island sign) and quantitative neuroimaging indicators (MS, IVHV) (AUC ± SE (95 % CI) = 0.92 ± 0.02 (0.89–0.95), р ˂ 0.0001). Conclusions. Non-contrast computed tomography markers of ICH expansion are associated with increased risk of END in patients with HHS. Hypodensity and island sign are independent predictors of END. The integration of NCCT markers of ICH expansion with quantitative neuroimaging indicators (MS, IVHV) in the structure of the multi-prediction logistic regression model allows to assess the individual risk of END with an accuracy of &gt;85.0 %.

Construction of a prediction model for risk of early neurological deterioration following intravenous thrombolysis in patients with acute ischemic stroke.

The etiology of early neurological deterioration (END) occurring after intravenous thrombolysis is unclear. To investigate the factors associated with END following intravenous thrombolysis in patients with acute ischemic stroke, and to construct a prediction model. We selected a total of 321 patients with acute ischemic stroke, who were divided into two groups: the END group (n= 91) and the non-END group (n= 230). They were compared for their demographics, onset-to-needle time (ONT), door-to-needle time (DNT), related score results, and other data. The risk factors of the END group were identified using logistic regression analysis, and we constructed a nomogram model using the R software. A calibration curve was used to evaluate the calibration of the nomogram, and we assessed its clinical applicability using decision curve analysis (DCA). In our multivariate logistic regression analysis, we found that four indexes, namely, complication with atrial fibrillation, post-thrombolysis National Institutes of Health Stroke Scale (NIHSS) score, pre-thrombolysis systolic blood pressure (SBP), and serum albumin level, were independent risk factors for END following intravenous thrombolysis in the patients (P< 0.05). We constructed an individualized nomogram prediction model using the above four predictors. The AUC value of the nomogram model was 0.785 (95% CI: 0.727-0.845) after internal validation, and the mean absolute error (MAE) in the calibration curve was 0.011, which indicated that the nomogram model had good prediction value. The decision curve analysis indicated that the nomogram model was clinically relevant. The model was found to have excellent value in clinical application and prediction of END. This will be beneficial for healthcare providers to develop individualized prevention measures for END in advance, and thus reduce the incidence of END following intravenous thrombolysis.

Systemic inflammation response index as a clinical outcome evaluating tool and prognostic indicator for hospitalized stroke patients: a systematic review and meta-analysis.

Stroke, which is the main element of cerebrovascular disease (CVD), has become the foremost reason for death and disability on a global scale. The systemic inflammation response index (SIRI), a newly developed and comprehensive indicator, has demonstrated promise in forecasting clinical results for diverse ailments. Nevertheless, the uncertainty surrounding the assessment and prediction of clinical outcomes for stroke patients by SIRI persists, and the conflicting findings from the limited studies conducted on this matter further complicate the situation. Consequently, we performed a thorough systematic review and meta-analysis to explore the correlation between SIRI and the clinical results in individuals suffering from stroke. This research was registered in PROSPERO and carried out following the PRISMA guidelines. A thorough investigation was carried out on PubMed, Embase, the Cochrane Library, Web of Science, and Scopus databases. Furthermore, we conducted a manual search in Chinese databases, such as China national Knowledge Infrastructure (CNKI), WanFang, VIP, and China Biology Medicine (CBM). We assessed the potential for bias in the studies included by utilizing the Newcastle-Ottawa Scale (NOS) tool. Adverse clinical outcomes were the main focus of the study, with secondary endpoints including mortality, the predictive value of SIRI, SIRI values across various endpoints, and clinical parameters associated with subarachnoid hemorrhage (SAH) in relation to low and high SIRI group. Following rigorous evaluation, a grand total of 22 investigations, encompassing a populace of 12,737 individuals, were considered suitable for incorporation in the final analysis. The findings from our meta-analysis indicate a strong and consistent correlation between elevated SIRI levels and adverse functional outcomes, irrespective of the method used to evaluate unfavorable outcomes. Furthermore, increased SIRI values have a strong correlation with mortality rates in both the short and long term. Besides, SIRI is a useful indicator of the severity of SAH. SIRI demonstrates strong predictive ability in identifying unfavorable outcomes and stroke-related pneumonia (SAP), as higher SIRI values are typically linked to negative endpoints. Nevertheless, the meta-analysis indicated that there was no significant increase in the risk of early neurological deterioration (END) and acute hydrocephalus (AHC) in high SIRI group when comparing to low SIRI. This study could potentially pave the way for groundbreaking insights into the relationship between SIRI and stroke patient outcomes, as it appears to be the first meta-analysis to explore this association. Given the critical role of the inflammatory response in stroke recovery, closely monitoring patients with high SIRI levels could represent a promising strategy for mitigating brain damage post-stroke. Thus, further investigation into SIRI and its impact on clinical outcomes is essential. While our initial findings offer valuable insights into this area, continued research is necessary to fully elucidate the potential of SIRI, ideally through dynamic monitoring and large-scale, multi-center studies. Ultimately, this research has the potential to inform clinical decision-making and improve patient outcomes following stroke. https://www.crd.york.ac.uk/prospero/ ; Identifier CRD42023405221.

Prognostic utility of sTREM-1 in predicting early neurological deterioration in patients with acute ischemic stroke treated without reperfusion therapy

ObjectiveSerum triggering receptor expressed on myeloid cells type 1 (sTREM-1) is a new type of immunoglobulin superfamily receptor related to inflammation that aggravates brain injury. This study aimed to assess the clinical value of sTREM-1 in predicting early neurological deterioration in patients with acute ischemic stroke (AIS) treated without reperfusion therapy. MethodsThis prospective cohort study enrolled 315 patients with acute ischemic stroke admitted to the Affiliated Taizhou People's Hospital of Nanjing Medical University between October 2020 and October 2022. The study excluded patients treated with reperfusion therapy. sTREM-1 levels were evaluated within 24 h of the acute ischemic stroke. Early neurological deterioration (END) was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points within three days after admission. Multivariable analyses were used to investigate the relationship between sTREM-1 levels and END. ResultsA total of 81 (25.7 %) patients had early neurological deterioration. Patients in the END group had a higher NIHSS score at admission (P =0.007), CRP levels (P =0.011), white blood cell count (P =0.002), fasting blood glucose levels (P =0.028), and sTREM-1 levels (P <0.001). After adjusting for confounders, higher sTREM-1 levels were significantly associated with an increased risk of early neurological deterioration (OR, 1.98; 95 % CI, 1.17-3.38, P=0.012). Moreover, sTREM-1 levels efficiently differentiated END (area under the curve: 0.779; 95 % CI: 0.731-0.822). Furthermore, the results showed significant differences between the high sTREM-1 group and the low sTREM-1 group in NIHSS scores (P=0.019), C-reactive protein (P=0.018), white blood cell count (P=0.013), and the incidence of early neurological deterioration (P<0.001). According to the multivariate logistic regression model, we discovered that the high sTREM-1 group was a significant independent predictor of early neurological deterioration incidence (OR, 4.19; 95 % CI, 1.46-9.84; P= 0.003). ConclusionsTREM-1 could be a potential biomarker for predicting early neurological deterioration in AIS patients not treated with reperfusion therapy.

Correlation between Increased Leukocyte Counts in Patients with Acute Phase Hemorrhagic Stroke with Early Neurological Deterioration Events

Stroke is the second most common cause of death and the leading cause of disability worldwide. Hemorrhagic stroke occurs in 15% of stroke cases. Increased leukocyte counts in the acute phase of hemorrhagic stroke are believed to be related to the incidence of early neurological deterioration. This study aims to determine the relationship between increased leukocyte count and early neurological deterioration in hemorrhagic stroke patients while being treated at UKI General Hospital. This research is analytic research with a cross-sectional design. There were 38 research subjects. The sample was selected using total sampling with specified inclusion and exclusion criteria. The study subjects were grouped into leukocytosis with leukocyte values &gt; 11,000/µL blood and normoleukocytes with leukocyte ranges ranging from 4000-11000/µL blood. The data used is secondary data. The results of the study were processed using the SPSS computer program. It was found that early neurological deterioration in patients with leukocytosis was significantly higher than in patients with normoleucosis, with a Relative Risk of early neurological deterioration in patients with leukocytosis of 3.003 (CI 95%); p=0.031). A significant relationship exists between increased leukocyte count (leukocytosis) upon admission and early neurological deterioration while being treated for hemorrhagic stroke patients at the UKI General Hospital.

Culprit Plaques of Large Parent Arteries, Rather than Cerebral Small Vessel Disease, Contribute to Early Neurological Deterioration in Stroke Patients with Intracranial Branch Atheromatous Disease

Introduction: Intracranial branch atheromatous disease (BAD) has been applied to occlusions that occur at the origin of large caliber penetrating arteries due to the microatheromas or large parent artery plaques. This study aimed to explore the association between culprit plaques of large parent arteries, neuroimaging markers of cerebral small vessel disease (CSVD), and the risk of early neurological deterioration (END) in stroke patients with BAD. Methods: A total of 97 stroke patients with BAD in the vascular territories of the lenticulostriate arteries or paramedian pontine arteries, diagnosed using high-resolution magnetic resonance imaging, were prospectively recruited in this observational study. A culprit plaque in the middle cerebral artery was defined as the only arterial plaque on the ipsilateral side of an infarction visible on diffusion-weighted imaging. A culprit plaque in the basilar artery (BA) was identified when it was observed within the same axial slices of an infarction or on the adjacent upper or lower slice, whereas a plaque within the BA located in the ventral region was considered non-culprit. If more than one plaque was present in the same vascular territory, the most stenotic plaque was chosen for the analysis. Four CSVD neuroimaging markers, including white matter hyperintensity, lacunes, microbleeds, and enlarged perivascular spaces, were evaluated in accordance with the total CSVD score. The associations between neuroimaging features of lesions within large parent arteries, neuroimaging markers of CSVD, and the risk of END in stroke patients with BAD were investigated using logistic regression analysis. Results: END occurred in 41 stroke patients (42.27%) with BAD. The degree of large parent artery stenosis (p < 0.001), culprit plaques of large parent arteries (p < 0.001), and plaque burden (p < 0.001) were significantly different between the END and non-END groups in stroke patients with BAD. In logistic regression analysis, culprit plaques of large parent arteries (odds ratio, 32.258; 95% confidence interval, 4.140–251.346) were independently associated with the risk of END in stroke patients with BAD. Conclusions: Culprit plaques of large parent arteries could predict the risk of END in stroke patients with BAD. These results suggest that lesions in the large parent arteries, rather than damage to the cerebral small vessels, contribute to END in stroke patients with BAD.

Serum neurofilament light chain levels are associated with early neurological deterioration in minor ischemic stroke.

Patients with minor ischemic stroke (MIS) frequently suffer from early neurological deterioration (END) and become disabled. Our study aimed to explore the association between serum neurofilament light chain (sNfL) levels and END in patients with MIS. We conducted a prospective observational study in patients with MIS [defined as a National Institutes of Health Stroke Scale (NIHSS) score 0-3] admitted within 24 h from the onset of symptoms. sNfL levels were measured at admission. The primary outcome was END, defined as an increase in the NIHSS score by ≥2 points within 5 days after admission. Univariate and multivariate analyses were performed to explore the risk factors associated with END. Stratified analyses and interaction tests were conducted to identify variables that might modify the association between sNfL levels and END. A total of 152 patients with MIS were enrolled, of which 24 (15.8%) developed END. The median sNfL level was 63.1 [interquartile range (IQR), 51.2-83.4] pg/ml on admission, which was significantly higher than that of 40 age- and sex-matched healthy controls (median 47.6, IQR 40.8-56.1 pg/ml; p < 0.001). Patients with MIS with END had a higher level of sNfL (with ND: median 74.1, IQR 59.5-89.8 pg/ml; without END: median 61.2, IQR 50.5-82.2 pg/ml; p = 0.026). After adjusting for age, baseline NIHSS score, and potential confounding factors in multivariate analyses, an elevated sNfL level (per 10 pg/mL) was associated with an increased risk of END [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.04-1.77; p = 0.027). Stratified analyses and interaction tests demonstrated that the association between sNfL and END did not change by age group, sex, baseline NIHSS score, Fazekas' rating scale, hypertension, diabetes mellitus, intravenous thrombolysis, and dual antiplatelet therapy in patients with MIS (all p for interaction > 0.05). END was associated with an increased risk of unfavorable outcomes (modified Rankin scale score ranging from 3 to 6) at 3 months. Early neurological deterioration is common in minor ischemic stroke and is associated with poor prognosis. The elevated sNfL level was associated with an increased risk of early neurological deterioration in patients with minor ischemic stroke. sNfL might be a promising biomarker candidate that can help to identify patients with minor ischemic stroke at high risk of neurological deterioration, for reaching individual therapeutic decisions in clinical practice.

Relationship of Serum IL-12 to Inflammation, Hematoma Volume, and Prognosis in Patients With Intracerebral Hemorrhage.

Objective Inflammatory cascades and hematomas after intracerebral hemorrhage (ICH) cause brain tissue and neuronal damage. Interleukin-12 (IL-12) promotes brain inflammation, and regulates coagulation mediated by red blood cells and platelets. This study was designed to investigate the relationship of serum IL-12 to inflammation, hematoma volume, and prognosis in ICH patients. Methods We recruited patients with ICH within 12 hours of symptom onset (n = 209) and measured their serum IL-12 levels. Patients with an increased National Institute of Health stroke scale (NIHSS) score ≥4 were defined as early neurological deterioration, and modified rankin scale (mRS) score >2 at 3 months after intracerebral hemorrhage was defined as poor prognosis. Results Levels of serum IL-12 was positively correlated with the admission of NIHSS scores (r = 0.535, P < 0.001), hematoma volume (r = 0.608, P < 0.001), serum CRP levels (r = 0.561, P < 0.001), and serum TNF-α levels (r = 0.533, P < 0.001) in 209 cases ICH patients. Levels of IL-12 in ICH patients with early neurological deterioration (median: 82.9 versus 65.8, P < 0.001) or with poor prognosis (median: 79.0 versus 65.3, P < 0.001) were all significantly higher than those in other ICH patients. In addition, serum IL-12 levels could be used to differentiate ICH patients at risk for early neurological deterioration with an AUC of 0.788 (95% CI: 0.717–0.858) or ICH patients at risk for suffering from an unfavorable outcome with an AUC of 0.787 (95% CI: 0.722–0.851). Conclusion Elevated admission serum IL-12 levels are closely related to the inflammation, hematoma volume, and prognosis in ICH patients. Substantializing serum IL-12 levels is a prognostic biomarker for ICH.

Serum neurofilament light chain and initial severity of neurological disease predict the early neurological deterioration in Wilson’s disease

BackgroundIn Wilson’s disease (WD), early neurological deterioration after treatment initiation is associated with poor outcomes; however, data on this phenomenon are limited. Our study analysed the frequency and risk factors of early neurological deterioration in WD.MethodsEarly neurological deterioration, within 6 months from diagnosis, was defined based on the Unified Wilson’s Disease Rating Scale (UWDRS): any increase in part II or an increase of ≥ 4 in part III. In total, 61 newly diagnosed WD patients were included. UWDRS scores, brain magnetic resonance imaging (MRI) scores, copper metabolism parameters, treatment type and serum neuro-filament light chain (sNfL) concentrations at diagnosis were analysed as potential risk factors of early deterioration.ResultsEarly neurological deterioration was observed in 16.3% of all WD patients; all cases of worsening occurred in the neurological phenotype (27.7%). Higher scores were seen in those who deteriorated compared with those who did not for UWDRS part II (4.3 ± 5.0 vs 2.0 ± 5.9; p < 0.05), UWDRS part III (21.5 ± 14.1 vs 9.3 ± 16.4; p < 0.01) and MRI-assessed chronic damage (3.2 ± 1.6 vs 1.4 ± 2.2; p = 0.006); all these variables indicated the initial severity of neurological disease. Pre-treatment sNfL concentrations were significantly higher in patients who deteriorated compared with those who did not (33.2 ± 23.5 vs 27.6 ± 62.7 pg/mL; p < 0.01). In univariate logistic regression amongst all patients, chronic damage MRI scores, UWDRS part III scores and sNfL concentrations predicated early deterioration. In the neurological WD, only sNFL were a significant predictor. In bivariate logistic regression amongst all patients, sNfL remained the only significant predictor of deterioration when corrected for MRI scores.ConclusionsNfL concentrations are a promising biomarker of the risk of early neurological deterioration in WD.

Association between serum netrin-1 levels and early neurological deterioration after acute ischemic stroke.

Background and purposesExperimental studies demonstrated that netrin-1 (NT-1) has anti-inflammatory, tissue regeneration, and immune modulation properties. We aimed to discern the utility of NT-1 as a biomarker for assessing the risk of early neurological deterioration (END) after ischemic stroke.MethodsThis was a prospective study enrolling ischemic stroke patients with symptoms onset <24 h. Serum NT-1 concentrations were measured at admission. The National Institutes of Health Stroke Scale increased by ≥2 points and ≥4 points during the first 72 h after admission and was defined as END2 and END4, respectively.ResultsThe study included 268 patients (146 men and 122 women) with a mean age of 63.0 ± 9.6 years. The median NT-1 concentrations were 466.4 pg/ml (interquartile range, 341.4–589.2 pg/ml). During the initial 72 h after admission, END2 was found in 83 (31.0%) patients, and END4 was observed in 48 (17.9%) subjects. After adjusted for potential confounders, multivariate analysis indicated that decreased NT-1 levels is an independent predictor for END2 [odds ratio (OR) 0.62, 95% confidence interval (CI) 0.46–0.84, p < 0.001) and END4 (OR 0.53, 95% CI 0.36–0.76, p < 0.001). Similar results were found when the NT-1 levels were analyzed as a categorical variable. Furthermore, restricted cubic spline analysis showed a linear association between NT-1 concentrations and the risk of END (END2, p = 0.006 for linearity; END4, p < 0.001 for linearity).ConclusionsOur results suggest that decreased NT-1 levels were significantly associated with a higher risk of END after ischemic stroke.

Malnutrition and the Risk of Early Neurological Deterioration in Elderly Patients with Acute Ischemic Stroke.

Background and PurposeThis study aimed to investigate the relationship between malnutrition and early neurological deterioration (END) in elderly patients with acute ischemic stroke in China.MethodsWe used the registry data in the Third Affiliated Hospital of Nantong University and Nanjing Brain Hospital from June 2019 to January 2021. Malnutrition risk was evaluated by controlling nutritional status score (CONUT), geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI) score, respectively. END was defined as an increment of at least two points in the total NIHSS score within three days after admission. We evaluated the relationship between malnutrition and END with multivariable logistic regression models and reclassification indexes.ResultsA total of 732 elderly patients with first-ever acute ischemic stroke were included in the study. 243 patients developed END. 5.7%, 21.4%, 4.6% patients were classified as moderate to severe malnutrition by CONUT, GNRI and PNI, respectively. Malnutrition was associated with the risk of END for CONUT (odds ratio [OR], 1.210; 95% confidence interval [CI] 1.092–1.341; P < 0.001), for GNRI (OR, 0.943; 95% CI, 0.919–0.967; P < 0.001), and for PNI (OR, 0.936; 95% CI, 0.908–0.965; P < 0.001) in multivariable logistic regression models using the back-ward selection method. The discriminative ability was 0.763 (95% CI, 0.727–0.798) for CONUT, 0.769 (95% CI, 0.733–0.805) for GNRI and 0.769 (95% CI, 0.733–0.805) for PNI after adjusting for confounders. Besides, adding malnutrition indexes into models made the prediction of END more accurate.ConclusionMalnutrition was associated with END in elderly Chinese patients with acute ischemic stroke.

Прогностична цінність сироваткової концентрації васкулярного ендотеліального фактору росту а у пацієнтів в гострому періоді спонтанного супратенторіального внутрішньомозкового крововиливу

The aim of the study – to evaluate the informativeness of serum vascular endothelial growth factor A levels in detection of short-term prognosis in acute period of spontaneous supratentorial intracerebral hemorrhage on the ground of conservative treatment. Materials and methods. Prospective cohort comparative study of the 89 patients in acute period of spontaneous supratentorial intracerebral hemorrhage was done on the ground of conservative treatment. The evaluation of neurological deficit level was performed by using Full Outline of Unresponsiveness coma scale, Glasgow scale and National Institute of Health Stroke Scale. Cerebral brain structures visualization was made by computed tomography. During 24 hours of hospitalization serum samples were collected and vascular endothelial growth factor A (VEGF-A) was measures by using ELISA method. Early neurological deterioration and unfavorable acute spontaneous supratentorial intracerebral hemorrhage period outcome (4-6 score by modified Rankin scale on the 21st day of the disease) were registered as combined clinical endpoints. Statistical operation was made with the help of correlation analysis, logistic regression analysis, ROC-analysis. Results. Patients with unfavorable course and spontaneous supratentorial intracerebral hemorrhage acute period outcome were characterized by higher serum VEGF-A values on the 1st day from admission, that correlates with the volume of intracerebral hemorrhage (R=0,21, p˂0,01), volume of secondary intraventricular hemorrhage (R=0,29, p˂0,01) and total volume of intracranial hemorrhage (R=0,31, p˂0,01). It was detected that evaluation of VEGF-A serum concentrations together with neurovisualization parameters (midline shift severity, volume of secondary intraventricular hemorrhage) as a part of multipredictive logistic regression model allow to detect individual risk of early neurological deterioration with the accuracy 89,9% (AUC±SE (95% CI) = 0,91±0,04 (0,83-0,96), р˂0,0001). Conclusions. Serum VEGF-A levels in patients with spontaneous supratentorial intracerebral hemorrhage on the 1st day from admission is an informative additional parameter for prognosis of early neurological deterioration on the ground of conservative treatment

The Relationship of the Type of Intracerebral Hemorrhage to Early Disease Evolution and Long-Term Prognosis After r-tPA Thrombolysis.

To investigate the relationship of different subtypes of intracerebral hemorrhage (ICH) to early disease evolution and long-term prognosis in patients with acute cerebral infarction after intravenous recombinant tissue plasminogen activator(r-tPA). Seventy ischemic stroke patients treated with intravenous r-tPA who underwent computed tomography (CT) within 24 hours after thrombolysis were divided into 4 types (hemorrhagic infarction type 1 [HI-1], HI-2, parenchymal hemorrhage type 1 [PH-1], or PH-2 which according to the size of the hematoma and the presence or absence of space-occupying effect). Early evolution of the disease was observed by the change in the National Institutes of Health Stroke Scale (NIHSS) score within 24 hours after thrombolysis. The long-term prognosis was assessed by the modified Rankin Scale (mRS) score at the third month. There were 17 (24.3%) patients with ICH. Compared with patients in the non-ICH group, HI did not affect early neurological function or clinical outcome at the third month. PH-1 did not increase the risk of early neurological deterioration; however, PH-1 has a tendency to increase the risk of death at the third month (50% vs 11.3%, P = 0.090). PH-2 was significantly related to early neurological deterioration (66.7% vs 3.8%, P < 0.001) and mortality at the third month (50.0% vs 11.3%, P = 0.040). Patients with different subtypes of ICH after thrombolysis have different clinical outcomes. PH-2 is significantly associated with early neurological deterioration and increases mortality at the third month.

阿司匹林联合氯吡格雷可降低携带CYP2C19*2功能减退等位基因的缺血性卒中患者早期神经功能恶化的风险

阿司匹林联合氯吡格雷可降低携带CYP2C19*2功能减退等位基因的缺血性卒中患者早期神经功能恶化的风险