Early Neurological Deterioration Research Articles

Early antiplatelet therapy after intravenous thrombolysis for acute ischemic stroke: a systematic review and meta-analysis.

Early neurological deterioration (END) and recurrence of vessel blockage frequently complicate intravenous thrombolysis (IVT) for acute ischemic stroke (AIS). Several studies have indicated the potential effectiveness of the early initiation (within < 24 h) of antiplatelet therapy (APT) after IVT. However, conflicting results have been reported by other studies. We aimed to offer a thorough overview of the current literature through a systematic review and meta-analysis. Our systematic review and meta-analysis were prospectively registered on PROSPERO (ID: CRD42023488173) following the PRISMA guidelines. We systematically searched Web of Science, SCOPUS, PubMed, and Cochrane Library until May 5, 2024. Rayyan. ai facilitated the screening process. The R statistical programming language was used to calculate the odds ratios and conduct a meta-analysis. Our primary outcomes were excellent functional recovery (modified Rankin Scale score 0-1), symptomatic intracranial hemorrhage (sICH), and mortality. Eight studies involving 2,134 participants were included in the meta-analysis. Early APT showed statistically significant increased odds of excellent functional recovery (mRS 0-1) compared to the standard APT group (OR, 1.81; [95% CI: 1.10, 2.98], p = 0.02). However, we found no differences between the early and standard APT groups regarding sICH (OR, 1.74; [95% CI: 0.91, 3.33], p = 0.10) and mortality (OR, 0.88; [95% CI: 0.62, 1.24]; p = 0.47). Early APT within 24 h of IVT in stroke patients is safe, with no increase in bleeding risk, and has a positive effect on excellent functional recovery. However, there was a statistically insignificant trend of increased sICH with early APT, and the current evidence is based on highly heterogeneous studies. Further large-scale RCTs are warranted.

Contrast enhancement after mechanical thrombectomy: clinical correlations and impact on outcomes.

Contrast enhancement (CE) after mechanical thrombectomy (MT) remains a subject of investigation, with a reported prevalence ranging from 31 to 88%. We examined our patients to identify predictors of CE and its impact on outcomes, an aspect that remains understudied. We retrospectively analyzed 106 patients who underwent MT at our hospital between 2018 and 2022. The inclusion criteria involved patients who underwent two head CT scans: one immediately after the procedure and a repeat scan within 24h. This study compared demographic, clinical, laboratory, neuroimaging, and procedure-related variables between patients with CE and those without hyperdensity. Regression analysis was employed to determine the associations between CEs and significant variables. Among the analyzed patients, 32.1% had CE. Hyperlipidemia was more prevalent in the CE group. CE correlated with an increase in the National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 within 24h, intracerebral hemorrhage (ICH) incidence, elevated NIHSS score, and a decreased rate of modified Rankin scale (mRS) 0-3 upon discharge. The adjusted model demonstrated a significant association between CE and the incidence of hyperlipidemia and ICH, with an increase in NIHSS score ≥ 4 within 24h of ICH and a lower mRS score of 0-3 upon discharge. CE is associated with hyperlipidemia, ICH, early neurological deterioration, and poor functional outcomes upon discharge. However, no similar association was shown for long-term outcomes. Further studies are required to clarify the pathophysiology of CE and its implications for optimizing stroke care.

Redefining Infarction Size for Small-Vessel Occlusion in Acute Ischemic Stroke: A Retrospective Case-Control Study.

Small-vessel occlusion, previously referred to as lacunar infarcts, accounts for approximately one-third of all ischemic strokes, using an axial diameter of less than 20 mm on diffusion-weighted imaging. However, this threshold may not adequately differentiate small-vessel occlusion from other pathologies, such as branch atheromatous disease (BAD) and embolism. This study aimed to assess the clinical significance and pathological implications of acute small subcortical infarctions (SSIs) based on infarct diameter. We conducted a retrospective case-control study using data from stroke patients recorded between 2016 and 2021 of the Stroke Registry in Chang Gung Healthcare System. Patients with acute SSIs in penetrating artery territories were included. Key variables such as patient demographics, stroke severity, and medical history were collected. Infarcts were categorized based on size, and the presence of early neurological deterioration (END) and favorable functional outcomes were assessed. Among the 855 patients with acute SSIs, the median age was 70 years and the median National Institutes of Health Stroke Scale (NIHSS) score at arrival was four. END occurred in 97 patients (11.3%). Those who experienced END were significantly less likely to achieve a favorable functional outcome compared to those who did not (18.6% vs. 59.9%, p < 0.001). The incidence of END increased progressively with infarct sizes of 15 mm or larger, with the optimal threshold for predicting END identified as 15.5 mm and for BAD, it was 12.1 mm. A multiple logistic regression analysis revealed that motor tract involvement [adjusted odds ratio (aOR) 2.3; 95% confidence interval (CI) 1.1-4.7], an initial heart rate greater than 90 beats per minute (aOR 2.3; 95% CI 1.2-4.3), and a larger infarct size (15 mm to less than 20 mm vs. 10 mm to less than 15 mm; aOR 3.0; 95% CI 1.4-6.3) were significantly associated with END. Our findings suggest that setting the upper limit for small-vessel occlusion at 15 mm would be more effective in distinguishing it from BAD. However, these findings should be interpreted in the context of the retrospective design and study population. Further multi-center research utilizing high-resolution vessel wall imaging is necessary to refine this threshold and enhance diagnostic accuracy.

Safety, feasibility, and acceptability of a novel device to monitor ischaemic stroke patients

This study assessed the safety, feasibility, and acceptability of a novel device to monitor ischaemic stroke patients. The device captured electroencephalography (EEG) and electrocardiography (ECG) data to compute an ECG-based metric, termed the Electrocardiography Brain Perfusion index (EBPi), which may function as a proxy for cerebral blood flow (CBF). Seventeen ischaemic stroke patients wore the device for nine hours and reported feedback at 1, 3, 6 and 9 h regarding user experience, comfort, and satisfaction (acceptability). Safety was assessed as the number of adverse events reported. Feasibility was assessed as the percentage of uninterrupted EEG/ECG data recorded (data capture efficiency). No adverse events were reported, only minor incidences of discomfort. Overall device comfort (mean ± 1 standard deviation (SD) (range)) (92.5% ± 10.3% (57.0–100%)) and data capture efficiency (mean ± 1 SD (range)) (95.8% ± 6.8% (54.8–100%)) were very high with relatively low variance. The device didn’t restrict participants from receiving clinical care and rarely (n = 6) restricted participants from undertaking routine tasks. This study provides a promising evidence base for the deployment of the device in a clinical setting. If clinically validated, EBPi may be able to detect CBF changes to monitor early neurological deterioration and treatment outcomes, thus filling an important gap in current monitoring options. TRIAL REGISTRATION: The study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000112763).

CT Perfusion imaging as prognostic factor for outcome of lacunar stroke.

Early neurological deterioration (END) affects 20-30% of patients with lacunar stroke within 48h despite optimal treatment. Previously established markers included infection and infarct location on imaging. We studied the utility of measuring global cerebral blood flow (gCBF) measured by CT-Perfusion (CTP) as an early predictor of END in patients with lacunar strokes. 162 patients with lacunar stroke were measured for gCBF including both cerebral hemispheres and cerebellum. We stratified patients by normal gCBF (> 40ml/100mg/min) vs. low gCBF (< 40ml/100mg/min). Stroke location, vascular risk factors, age and gender were assessed. The primary outcome was the change in the NIHSS score after 48h from index stroke. Mean gCBF of the overall cohort was 37.72ml/100mg/min. Both groups had a baseline NIHSS score of 4.2 with similar standard deviations. The NIHSS score decreased by 1.3 points in normal gCBF group and increased by 1.1 points in the low gCBF group. All stroke sites deteriorated in the low gCBF group, particularly the capsula interna, corona radiata, and lateral pontine area. END occurred in 37.8% in low gCBF compared to 3.1% in the normal gCBF patients. In contrast, clinical improvement after 48h occurred in 64.2% of patients with normal gCBF but only 6.1% with low gCBF. Our study supports measurement of gCBF by CTP as a potential imaging biomarker for END. Additionally, it adds evidence to the body of supporting the vulnerability of capsula interna and pontine infarctions to END.

Dual Antiplatelet Versus Alteplase for Early Neurologic Deterioration in Minor Stroke With Versus Without Large Vessel Occlusion: Prespecified Post Hoc Analysis of the ARAMIS Trial.

Dual antiplatelet therapy (DAPT) was noninferior to alteplase in minor nondisabling strokes in the ARAMIS trial (Antiplatelet Versus R-tPA for Acute Mild Ischemic Stroke); however, early neurological deterioration (END) associated with vessel stenosis may benefit from DAPT. We investigated whether the efficacy of DAPT was greater than alteplase in minor strokes with no large vessel occlusion (LVO). This study was a prespecified post hoc analysis of the ARAMIS trial and included patients with responsible vessel examination in the as-treated analysis set of the ARAMIS trial who were divided into LVO group and non-LVO group. In each group, patients were further classified into DAPT and intravenous alteplase treatments. Primary outcome was END at 24 hours defined as more than or equal to 4-point National Institutes of Health Stroke Scale score increase compared with baseline, and safety outcomes were symptomatic intracerebral hemorrhage and bleeding events during study. The primary analysis was estimated with a risk difference calculated by a generalized linear model including adjusted different baseline characteristics between treatments. Of 723 patients from the ARAMIS trial, 480 patients were included: 36 were categorized into LVO group and 444 into non-LVO group, of whom 20 patients had END. Compared with intravenous alteplase, a lower proportion of END was found after DAPT treatment in the non-LVO group (adjusted risk difference, -4.8% [95% CI, -6.9% to -2.6%]; P<0.001), but not in the LVO group (adjusted risk difference, 2.3% [95% CI, -17.6% to 22.3%]; P=0.82). The interaction was marginally significant between groups (P=0.06). In the non-LVO group, a lower proportion of bleeding events was found after DAPT treatment than intravenous alteplase (adjusted risk difference, -6.4% [95% CI, -8.9% to -3.9%]; P<0.001). Other safety outcomes were similar between the 2 treatments. Among minor nondisabling acute ischemic stroke without LVO, DAPT may be superior to intravenous alteplase regarding preventing END with a better safety profile. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03661411.

Nomogram for predicting early neurological deterioration in patients with mild large and medium vessel occlusion stroke intended for medical management: a multicenter retrospective study

BackgroundAccurately forecasting early neurological deterioration of ischemic origin (ENDi) following medical management may aid in identifying candidates for thrombectomy. We aimed to develop and validate a nomogram to predict ENDi...

Urinary Microalbumin predicts early neurological deterioration in acute ischemic stroke: A study based on etiological classification

IntroductionTo investigate the correlation between urinary microalbumin (U-Alb) levels and early neurological deterioration (END), as well as its predictive ability, in patients with acute ischemic stroke (AIS) under different etiological subtypes. Materials and methodsWe consecutively enrolled AIS patients within 72 h of onset, collecting relevant clinical characteristics and baseline laboratory data including U-Alb. END was defined as an increase of ≥4 points in NIHSS score within 72 h of onset, and TOAST criteria were used for stroke etiologic typing. Binary logistic regression analysis was employed to clarify the association between baseline U-Alb and the occurrence of END under different stroke etiological subtypes. ROC analysis was conducted to evaluate its predictive ability under different etiological subtypes. ResultsFinally, 615 patients were included, with 104 (16.9 %) developed END. Binary logistic regression analysis revealed that baseline U-Alb was independently associated with END occurrence (OR = 1.009, 95 % CI 1.002-1.016, p = 0.009). ROC analysis revealed that U-Alb had the best predictive ability for patients with small artery occlusion (AUC=0.707, p < 0.001), followed by large artery atherosclerosis (AUC = 0.632, p = 0.006), with corresponding optimal diagnostic cutoff points of 31.11 and 25.71 mg/L, respectively. However, U-Alb was not an independent risk factor for END in cardioembolic stroke patients (OR = 1.011, 95 % CI 0.980-1.043, p = 0.478). MAU was associated with stroke progression(p = 0.023), and U-Alb was positively correlated with increased infarct volume (r = 0.516, p < 0.01). ConclusionU-Alb is closely associated with END in AIS patients, serving as a potential indicator for predicting END, especially among those with small artery occlusion mechanisms.

Clinical and Prognostic Characteristics of Acute BAD-Related Stroke: A Multicenter MRI-Based Prospective Study.

Branch atheromatous disease (BAD)-related stroke has emerged as a meaningful subtype of ischemic stroke yet remained understudied. We aimed to investigate the demographic, clinical, therapeutic, and prognostic characteristics of BAD-related stroke. The BAD-study was a nationwide, multicenter, prospective, observational cohort study in 20 Chinese hospitals from June 2021 to June 2023, enrolling patients aged 18 to 80 years with BAD-related stroke within 72 hours of onset. Eligible single subcortical infarct in the territory of lenticulostriate artery and paramedian pontine artery was included. Clinical, laboratory, and treatment data were collected at baseline. The primary outcome was a proportion of good outcomes (modified Rankin Scale score, 0-2) at 90 days. Main secondary outcomes included early neurological deterioration (END), cerebrovascular event, major bleeding, and excellent outcome (modified Rankin Scale score, 0-1) during 90-day follow-up. We finally enrolled 476 patients, with a median age of 60 (interquartile range, 53-68) years, and 70.2% were male. The median National Institutes of Health Stroke Scale score was 3 (interquartile range, 2-6) at enrollment. Involvement of the lenticulostriate artery was more common than the paramedian pontine artery (60.7% versus 39.3%). END occurred in 14.7% of patients, with a median time from onset of 38 (interquartile range, 22-62) hours. The rates of good and excellent outcomes were 86.5% and 72%, respectively. Its 90-day stroke recurrence rate was 1.9%. Acute-phase therapy (from onset to 7 days of enrollment) showed heterogeneity and was not associated with prognosis. Multivariable logistic regression analysis identified the National Institutes of Health Stroke Scale score ≥4 at admission and END as negative predictors and extracranial artery stenosis as a positive predictor of good outcomes. Age ≥60 years, National Institutes of Health Stroke Scale score ≥4 at admission, and END were negative predictors of excellent outcomes. With distinct demographic, clinical, and prognostic characteristics, along with a high incidence of END and a low risk of stroke recurrence, BAD-related stroke could be categorized as a separate disease entity. Moreover, its acute-phase treatment strategies were undetermined, awaiting further high-quality studies.

Systemic Inflammation Predict Neurological Functional Outcome in Patients with Tuberculous Meningitis: A Multicenter Retrospective Cohort Study in China.

The predictors associated with clinical outcomes in patients with tuberculous meningitis (TBM) remain unclear. We aimed to analyse the relationship between systemic inflammation and clinical outcomes, as well as to explore whether systemic inflammation level influences the effectiveness of dexamethasone on treatment. Between January 2011 and December 2021, TBM patients admitted to five hospitals were observed consecutively. Baseline and post-treatment systemic inflammation levels were calculated using the neutrophil-lymphocyte-ratio (NLR). Generalized linear mixed models were employed to identify predictors of clinical outcomes. Propensity score matching and subgroup analyses were conducted to evaluate the effect of dexamethasone on treatment outcomes across different NLR levels. A total of 1203 TBM patients were included in the study. During the follow-up, 144 (13.6%) participants experienced early neurological deterioration within 7 days after admission, and 345 (28.67%) exhibited poor functional outcome at the 12-month follow-up. Multivariate analysis revealed that post-treatment NLR was significantly associated with early neurological deterioration (OR=1.25; 95% CI, 1.14-1.33; P<0.001), and poor outcome (OR=1.34; 95% CI, 1.26-1.45; P<0.001). After propensity score matching, dexamethasone treatment was not associated with early neurological deterioration (OR=0.83; 95% CI, 0.42-1.66; P=0.610) or poor outcome (OR=1.22; 95% CI, 0.49-2.11; P=0.490) in the highest quartile of post-treatment NLR. The effect of dexamethasone on treatment outcomes did not significantly vary with disease severity stratification. Elevated systemic inflammation is an independent risk factor for neurological outcome in TBM patients. Further studies are required to investigate systemic inflammation in more severely affected population to better predict the outcomes following anti-inflammatory therapies.

Is Thrombectomy Effective for Large Vessel Occlusion Stroke Patients with Mild Symptoms? Meta-Analysis and Trial Sequential Analysis

Background: Endovascular treatment (EVT) is an established method for managing large vessel occlusion (LVO), but its efficacy in patients with mild stroke (National Institutes of Health Stroke Scale [NIHSS] score &lt; 6) remains debated. Given the clinical problem of early neurological deterioration in approximately 10% of mild stroke patients, understanding the role of EVT in managing these patients is crucial. Our objective was to perform a meta-analysis with trial sequential analysis (TSA) focusing on mild stroke patients with LVO to determine whether EVT offers better outcomes than best medical therapy alone. Methods: A comprehensive search of PubMed, Cochrane, and Embase databases up to 12 December 2023 identified 14 retrospective and prospective cohort studies, including a total of 4436 patients with NIHSS scores less than 6 and presenting with LVO. Studies were categorized into crossover and non-crossover groups to prevent overestimation of the treatment effect. In the crossover group, patients initially treated with BMT were moved to EVT upon clinical deterioration. In the non-crossover group, patients remained in their initially assigned treatment. Meta-analysis and data extraction followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome was achieving an excellent functional outcome, defined as a modified Rankin scale (mRS) score of 0–1 at 3 months. Secondary outcomes included good (mRS 0–2) and favorable (mRS 0–3) functional outcomes. Safety outcomes were symptomatic intracerebral hemorrhage (sICH) and mortality at 3 months. Results: In the crossover group, EVT did not significantly improve excellent functional outcomes, and TSA results were inconclusive. Conversely, in the non-crossover group, EVT significantly improved the excellent functional outcome rates at 3 months (65.0% vs. 53.7%; OR 1.62; 95% CI 1.13 to 2.32), supported by TSA. EVT increased the risk of sICH in both crossover and non-crossover groups, while mortality rates did not significantly differ between EVT and BMT groups. Conclusions: Our research indicates that thrombectomy may not significantly help mild stroke patients in recovering functional status and could increase the risk of sICH. The disparity in results between crossover and non-crossover studies highlights the critical need for the prompt identification of patients at risk of early neurological deterioration to minimize negative outcomes. Additional randomized controlled trials are essential to optimize the application of EVT in this patient population.

Early Neurological Deterioration and Time to Start Dual Antiplatelet Therapy in Patients With Acute Mild-to-Moderate Ischemic Stroke: A Pre-Specified Post Hoc Analysis of the ATAMIS Trial.

This study comprised a post hoc analysis of the Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke (ATAMIS) trial aiming to determine whether the effect of dual antiplatelet therapy compared with that of monotherapy on preventing early neurological deterioration (END) differed according to the time from stroke onset to antiplatelet therapy (OTT). In the ATAMIS trial, patients were divided into two subgroups: OTT from 0 to 24 hours (0-24 h group) and OTT from 24 to 48 hours (24-48 h group). We conducted multivariate regression analysis with continuous and categorical OTT to detect the effect of antiplatelet therapy. The primary outcome was END at 7 days, defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score of more than two points compared with the baseline. The safety outcomes were bleeding events and intracranial hemorrhage within 90 days. A total of 2,915 patients were included. With respect to END at 7 days, clopidogrel plus aspirin showed a lower proportion than aspirin alone across continuous OTT (4.8% vs. 6.7%; adjusted risk difference, -1.9%; 95% confidence interval [CI], -3.6% to -0.2%; P=0.03), and was lower in the 0-24 hours group (5.7% vs. 9.2%; adjusted risk difference, -3.7%; 95% CI, -5.5% to -2.0%; P<0.01), but similar in the 24-48 hours group (3.5% vs. 2.9%; adjusted risk difference, 0.6%; 95% CI, -0.8% to 2.0%; P=0.40). We identified a significant interaction between the treatment effect and time subgroup with respect to the primary outcome (P=0.03). The occurrence of bleeding events and intracranial hemorrhage was similar in the time subgroup. For patients with acute mild-to-moderate ischemic stroke, clopidogrel plus aspirin was associated with a lower risk of END at 7 days than aspirin alone when it was started within 24 hours of symptom onset.

Platelet-to-neutrophil ratio predicts hemorrhagic transformation and unfavorable outcomes in acute ischemic stroke with intravenous thrombolysis.

Acute ischemic stroke (AIS) retains a notable stance in global disease burden, with thrombolysis via recombinant tissue plasminogen activator (rtPA) serving as a viable management approach, albeit with variable outcomes and the potential for complications like hemorrhagic transformation (HT). The platelet-to-neutrophil ratio (P/NR) has been considered for its potential prognostic value in AIS, yet its capacity to predict outcomes following rtPA administration demands further exploration. To elucidate the prognostic utility of P/NR in predicting HT and clinical outcomes following intravenous rtPA administration in AIS patients. Data from 418 AIS patients treated with intravenous rtPA at Thammasat University Hospital from January 2018 to June 2021 were retrospectively analyzed. The relationship between P/NR and clinical outcomes [early neurological deterioration (E-ND), HT, delayed ND (D-ND), and 3-mo outcomes] was scrutinized. Notable variables, such as age, diabetes, and stroke history, exhibited statistical disparities when comparing patients with and without E-ND, HT, D-ND, and 3-mo outcomes. P/NR prognostication revealed an optimal cutoff of 43.4 with a 60.3% sensitivity and a 52.5% specificity for 90-d outcomes. P/NR prognostic accuracy was statistically significant for 90-d outcomes [area under the curve (AUC) = 0.562], D-ND (AUC = 0.584), and HT (AUC = 0.607). P/NR demonstrated an association with adverse 3-mo clinical outcomes, HT, and D-ND in AIS patients post-rtPA administration, indicating its potential as a predictive tool for complications and prognoses. This infers that a diminished P/NR may serve as a novel prognostic indicator, assisting clinicians in identifying AIS patients at elevated risk for unfavorable outcomes following rtPA therapy.

Dual Antiplatelet Therapy and Outcomes in Acute Mild to Moderate Stroke With Versus Without Large-Artery Atherosclerosis Post Hoc Analysis of ATAMIS.

We conducted a post hoc analysis of the ATAMIS (Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke) trial to investigate whether the priority of clopidogrel plus aspirin to aspirin alone was consistent between patients with and without stroke pathogenesis of large-artery atherosclerosis (LAA). Patients with stroke classification randomized to a clopidogrel-plus-aspirin group and aspirin-alone group in a modified intention-to-treat analysis set of ATAMIS were classified into LAA and non-LAA subtypes. The primary outcome was early neurologic deterioration at 7 days, defined as a >2-point increase in National Institutes of Health Stroke Scale score compared with baseline, and safety outcomes were bleeding events and intracranial hemorrhage. We compared treatment effects in each stroke subtype and investigated the interaction. Among 2910 patients, 225 were assigned into the LAA subtype (119 in the clopidogrel-plus-aspirin group and 106 in the aspirin-alone group) and 2685 into the non-LAA subtype (1380 in the clopidogrel-plus-aspirin group and 1305 in the aspirin-alone group). Median age was 66 years, and 35% were women. A lower proportion of early neurologic deterioration was found to be associated with dual antiplatelet therapy in the LAA subtype (adjusted risk difference, -10.4% [95% CI, -16.2% to -4.7%]; P=0.001) but not in the non-LAA subtype (adjusted risk difference, -1.4% [95% CI, -2.6% to 0.1%]; P=0.06). No significant interaction was found (P=0.11). Compared with the non-LAA subtype, patients with stroke of the LAA subtype may get more benefit from dual antiplatelet therapy with clopidogrel plus aspirin with respect to early neurologic deterioration at 7 days. URL: clinicaltrials.gov; UnIque identifier: NCT02869009.

Machine learning-based prediction of early neurological deterioration after intravenous thrombolysis for stroke: insights from a large multicenter study.

This investigation seeks to ascertain the efficacy of various machine learning models in forecasting early neurological deterioration (END) following thrombolysis in patients with acute ischemic stroke (AIS). Employing data from the Shenyang Stroke Emergency Map database, this multicenter study compiled information on 7,570 AIS patients from 29 comprehensive hospitals who received thrombolytic therapy between January 2019 and December 2021. An independent testing cohort was constituted from 2,046 patients at the First People's Hospital of Shenyang. The dataset incorporated 15 pertinent clinical and therapeutic variables. The principal outcome assessed was the occurrence of END post-thrombolysis. Model development was executed using an 80/20 split for training and internal validation, employing classifiers like logistic regression with lasso regularization (lasso regression), support vector machine (SVM), random forest (RF), gradient-boosted decision tree (GBDT), and multi-layer perceptron (MLP). The model with the highest area under the curve (AUC) was utilized to delineate feature significance. Baseline characteristics showed variability in END incidence between the training (n = 7,570; END incidence 22%) and external validation cohorts (n = 2,046; END incidence 10%; p < 0.001). Notably, all machine learning models demonstrated superior AUC values compared to the reference model, indicating their enhanced predictive capacity. The lasso regression model achieved the highest AUC at 0.829 (95% CI: 0.799-0.86; p < 0.001), closely followed by the MLP model with an AUC of 0.828 (95% CI: 0.799-0.858; p < 0.001). The SVM, RF, and GBDT models also showed commendable AUCs of 0.753, 0.797, and 0.774, respectively. Decision curve analysis revealed that the SVM and MLP models demonstrated a high net benefit. Feature importance analysis emphasized "Onset To Needle Time" and "Admission NIHSS Score" as significant predictors. Our research establishes the MLP and lasso regression as robust tools for predicting early neurological deterioration in acute ischemic stroke patients following thrombolysis. Their superior predictive accuracy, compared to traditional models, highlights the significant potential of machine learning approaches in refining prognosis and enhancing clinical decisions in stroke care management. This advancement paves the way for more tailored therapeutic strategies, ultimately aiming to improve patient outcomes in clinical practice.

Rescue therapy of early neurological deterioration in lacunar stroke

BackgroundEarly neurological deterioration (END) occurs in many patients with acute ischemic stroke due to a variety of causes. Although pharmacologically induced hypertension (PIH) and anticoagulants have been investigated in several clinical trials for the treatment of END, the efficacy and safety of these treatments remain unclear. Here, we investigated whether PIH or anticoagulation is better as a rescue therapy for the progression of END in patients with lacunar stroke.MethodsThis study included patients with lacunar stroke who received rescue therapy with END within 3 days of symptom onset between April 2014 and August 2021. In the PIH group, phenylephrine was administered intravenously for 24 h and slowly tapered when symptoms improved or after 5 days of PIH. In the anticoagulation group, argatroban was administered continuously intravenously for 2 days and twice daily for next 5 days. We compared END recovery, defined as improvement in NIHSS from baseline, excellent outcomes (0 or 1 mRS at 3 months), and safety profile.ResultsAmong the 4818 patients with the lacunar stroke, END occurred in 147 patients. Seventy-nine patients with END received PIH (46.9%) and 68 patients (46.3%) received anticoagulation therapy. There was no significant difference in age (P = 0.82) and sex (P = 0.87) between the two groups. Compared to the anticoagulation group, the PIH group had a higher incidence of END recovery (77.2% vs. 51.5%, P < 0.01) and excellent outcomes (34.2% vs. 16.2%, P = 0.04). PIH was associated with END (HR 2.49; 95% CI 1.06–5.81, P = 0.04). PIH remained associated with END recovery (adjusted HR 3.91; 95% CI 1.19–12.90, P = 0.02). Safety outcomes, like hemorrhagic conversion and mortality, were not significantly different between the two groups.ConclusionsAs a rescue therapy for the progression of END in lacunar stroke patients, PIH with phenylephrine was more effective with similar safety compared to anticoagulation with argatroban.

Early neurological deterioration in acute lacunar ischemic stroke: Systematic review of incidence, mechanisms, and prospects for treatment.

Cerebral small vessel disease (CSVD) causes between 25% and 30% of all ischemic strokes. In acute lacunar ischemic stroke, despite often mild initial symptoms, early neurological deterioration (END) occurs in approximately 15-20% of patients and is associated with poor functional outcome, yet its mechanisms are not well understood. In this review, we systematically evaluated data on: (1) definitions and incidence of END, (2) mechanisms of small vessel occlusion, (3) predictors and mechanisms of END, and (4) prospects for the prevention or treatment of patients with END. We identified 67 reports (including 13,407 participants) describing the incidence of END in acute lacunar ischemic stroke. The specified timescale for END varied from <24 h to 3 weeks. The rate of END ranged between 2.3% and 47.5% with a pooled incidence of 23.54% (95% confidence interval (CI) = 21.02-26.05) but heterogeneity was high (I2 = 90.29%). The rates of END defined by National Institutes of Health Stroke Scale (NIHSS) decreases of ⩾1, ⩾2, ⩾3, and 4 points were as follows: 24.17 (21.19-27.16)%, 22.98 (20.48-25.30)%, 23.33 (16.23-30.42)%, and 10.79 (2.09-23.13)%, respectively, with lowest heterogeneity and greatest precision for a cutoff of ⩾2 points. Of the 20/67 studies (30%) reporting associations of END with clinical outcome, 19/20 (95%) reported worse outcomes (usually measured using the modified Rankin score at 90 days or at hospital discharge) in patients with END. In a meta-regression analysis, female sex, hypertension, diabetes, and smoking were associated with END. END occurs in more than 20% of patients with acute lacunar ischemic stroke and might provide a novel target for clinical trials. A definition of an NIHSS ⩾2 decrease is most used and provides the best between-study homogeneity. END is consistently associated with poor functional outcome. Further research is needed to better identify patients at risk of END, to understand the underlying mechanisms, and to carry out new trials to test potential interventions.

Associations of serum Dickkopf-1 levels with disease severity and 90-day Prognosis after spontaneous intracerebral hemorrhage: results from the prospective cohort study.

Dickkopf-1 (DKK-1) may be involved in inflammatory response and secondary brain injury after acute brain injury. We gauged serum DKK-1 levels and further assessed its correlation with disease severity and investigated its predictive value for 90-day prognosis in patients with spontaneous intracerebral hemorrhage (sICH). Serum DKK-1 levels were measured in 128 sICH patients and 128 healthy controls. The severity of sICH was assessed using the Glasgow Coma Scale (GCS) scores and hematoma volumes. Poor prognosis was referred to as a Glasgow Outcome Scale (GOS) score of 1-3 at 90days after stroke. Multivariate analysis was performed to identify associations of serum DKK-1 levels with disease severity, early neurological deterioration (END) and poor prognosis. Receiver operating characteristic curve (ROC) was built to investigate the prognostic predictive capability. The serum DKK-1 levels of patients were significantly higher than those of controls (median, 4.74ng/mL versus 1.98ng/mL; P < 0.001), and were independently correlated with hematoma volumes (ρ = 0.567, P < 0.001; t = 3.444, P = 0.001) and GCS score (ρ = -0.612, P < 0.001; t = -2.048, P = 0.043). Serum DKK-1 significantly differentiated patients at risk of END (area under ROC curve (AUC), 0.850; 95% confidence interval (CI), 0.777-0.907; P < 0.001) and poor prognosis (AUC, 0.830; 95% CI, 0.753-0.890; P < 0.001), which had similar prognostic ability, as compared to GCS scores and hematoma volumes. Subsequent Logistic regression model affirmed that GCS score, hematoma volume, and serum DKK-1 levels were independently associated with END and poor prognosis at 90days after sICH. The models, which contained them, performed well using ROC curve analysis and calibration curve analysis. Serum DKK-1 levels are markedly associated with disease severity, END and 90-day poor prognosis in sICH. Hence, serum DKK-1 is presumed to be used as a potential prognostic biomarker of sICH.

Defining short-term outcomes of minor ischemic stroke due to small artery occlusion in the era of dual antiplatelet treatment: A READAPT study sub-analysis

BackgroundThe outcomes of minor ischemic stroke resulting from small artery occlusion (SAO-MIS) have not yet been characterized after dual antiplatelet treatment (DAPT) has become the standard of care. We provided updated figures on the short-term prognosis of SAO-MIS treated with early short-term DAPT and compared the outcomes of SAO-MIS versus non-SAO-MIS patients. MethodsThis is a prespecified sub-analysis from a prospective multicentric real-world study (READAPT, NCT05476081) including patients with minor (NIHSS≤5) non-cardioembolic ischemic stroke treated with DAPT. The primary outcome was a composite of 90-day symptomatic ischemic stroke or major cardiovascular events. Secondary outcomes were the 90-day ordinal distribution of modified Rankin Scale (mRS) scores, 90-day excellent functional outcome (mRS of 0 to 1), and 24-h early neurological deterioration (END). Safety outcomes were 90-day intracerebral hemorrhage, moderate-to-severe and any bleedings. All outcomes were compared between SAO-MIS and non-SAO-MIS patients. ResultsWe included 678 MIS, of whom 253 (37.3 %) were SAO-related. At 90 days, 3 patients with SAO-MIS had primary outcome (1.2 % [95 % CI 0.2 %–3.5 %]), which were all SAO-related ischemic strokes. For the secondary outcomes, most SAO-MIS patients (n = 191, 75.5 %) had 90-day excellent functional outcome and 12 had 24-h END (4.7 % [95 % CI 2.5 %–8.3 %]). Referring to safety outcomes, 90-day intracerebral hemorrhage occurred only in one patient with SAO-MIS (0.4 % [95 % CI 0.0 %- 2.2 %]). Compared to non-SAO-MIS, the 90-day risk of recurrent vascular events was significantly lower among SAO-MIS (aHR 0.24 [95 % CI 0.08–0.68]; p = 0.007), while there were not significant differences in other secondary outcomes, nor in the risk of safety events. ConclusionsOur findings show overall favorable short-term prognosis after SAO-MIS treated with DAPT. Future studies should investigate factors associated with residual stroke risk and long-term outcomes of SAO-MIS.

Clinical features and predictors of early neurological deterioration in patients with Trousseau syndrome-related cerebral infarction

Objective: This study aimed to explore the clinical features of Trousseau syndrome (TS)-related cerebral infarction and determine predictors of early neurological deterioration (END). Methods: A retrospective study was conducted on patients with TS-related cerebral infarction admitted to the Zhongshan Hospital Affiliated with Xiamen University, from December 2015 to December 2023. Patients were categorized into groups with and without END. The laboratory findings and imaging data were compared, and receiver operating characteristic (ROC) curves were constructed to determine the best predictors of END. Results: The study included 30 patients with TS-related cerebral infarction, comprising 17 males and 13 females with an average age of 70.93 ± 8.7 years. Five patients experienced END. Lung cancer was the most common primary malignancy (n=13, 43.33%), with most patients (n=22, 73.33%) having stage IV disease with extensive metastasis. The primary neurological symptom was hemiplegia (n=17, 56.67%). The mean NIHSS score at admission was 9.33 ± 5.83. Imaging revealed varying stages of cerebral infarction in 10 patients (38.46%). Within three months, 25 patients (83.33%) died, 8 of whom (32%) succumbed to tumor-related complications. The incidence of END in TS-related cerebral infarction patients was 16.67% (5/30). Patients in the END group had significantly greater D-dimer levels and lower fibrinogen (Fib) levels upon admission (P &lt; 0.001, P = 0.042). Comparisons of ROC curves revealed that D-dimer (AUC 0.916, optimal cutoff 17.86, sensitivity 1.000, specificity 0.840) and Fib (AUC 0.788, optimal cutoff 2.54, sensitivity 1.000, specificity 0.740) significantly predicted END (P = 0.004, P = 0.045). The combined use of these markers improved the AUC to 0.952, with a sensitivity of 1.00 and specificity of 0.920, surpassing those of the individual markers (P = 0.002). Conclusion: TS-related cerebral infarction most commonly occurs in patients with advanced-stage lung cancer with widespread metastasis and is associated with poor long-term prognosis. Elevated D-dimer and decreased fibrinogen levels are significant predictors of END in patients with TS-related cerebral infarction.