Severity Of White Matter Lesions Research Articles

Association of plasma GFAP with elevated brain amyloid is dependent on severity of white matter lesions in an Asian cognitively impaired cohort.

While elevated blood glial fibrillary acidic protein (GFAP) has been associated with brain amyloid pathology, whether this association occurs in populations with high cerebral small vessel disease (CSVD) concomitance remains unclear. Using a Singapore-based cohort of cognitively impaired subjects, we assessed associations between plasma GFAP and neuroimaging measures of brain amyloid and CSVD, including white matter hyperintensities (WMH). We also examined the diagnostic performance of plasma GFAP in detecting brain amyloid beta positivity (Aβ+). When stratified by WMH status, elevated brain amyloid was associated with higher plasma GFAP only in the WMH- group (β=0.383; P<0.001). The diagnostic performance of plasma GFAP in identifying Aβ+ was significantly higher in the WMH- group (area under the curve [AUC]=0.896) than in the WMH+ group (AUC=0.712, P=0.008). The biomarker utility of plasma GFAP in detecting brain amyloid pathology is dependent on the severity of concomitant WMH. Glial fibrillary acidic protein (GFAP)'s association with brain amyloid is unclear in populations with high cerebral small vessel disease (CSVD).Plasma GFAP was measured in a cohort with CSVD and brain amyloid.Plasma GFAP was better in detecting amyloid in patients with low CSVD versus high CSVD.Biomarker utility of GFAP in detecting brain amyloid depends on the severity of CSVD.

Electrical stimulation of the cuneiform nucleus enhances the effects of rehabilitative training on locomotor recovery after incomplete spinal cord injury.

Most human spinal cord injuries are anatomically incomplete, leaving some fibers still connecting the brain with the sublesional spinal cord. Spared descending fibers of the brainstem motor control system can be activated by deep brain stimulation (DBS) of the cuneiform nucleus (CnF), a subnucleus of the mesencephalic locomotor region (MLR). The MLR is an evolutionarily highly conserved structure which initiates and controls locomotion in all vertebrates. Acute electrical stimulation experiments in female adult rats with incomplete spinal cord injury conducted in our lab showed that CnF-DBS was able to re-establish a high degree of locomotion five weeks after injury, even in animals with initially very severe functional deficits and white matter lesions up to 80-95%. Here, we analyzed whether CnF-DBS can be used to support medium-intensity locomotor training and long-term recovery in rats with large but incomplete spinal cord injuries. Rats underwent rehabilitative training sessions three times per week in an enriched environment, either with or without CnF-DBS supported hindlimb stepping. After 4 weeks, animals that trained under CnF-DBS showed a higher level of locomotor performance than rats that trained comparable distances under non-stimulated conditions. The MLR does not project to the spinal cord directly; one of its main output targets is the gigantocellular reticular nucleus in the medulla oblongata. Long-term electrical stimulation of spared reticulospinal fibers after incomplete spinal cord injury via the CnF could enhance reticulospinal anatomical rearrangement and in this way lead to persistent improvement of motor function. By analyzing the spared, BDA-labeled giganto-spinal fibers we found that their gray matter arborization density after discontinuation of CnF-DBS enhanced training was lower in the lumbar L2 and L5 spinal cord in stimulated as compared to unstimulated animals, suggesting improved pruning with stimulation-enhanced training. An on-going clinical study in chronic paraplegic patients investigates the effects of CnF-DBS on locomotor capacity.

Diurnal cortisol, neuroinflammation, and neuroimaging visual rating scales in memory clinic patients

BackgroundNeuroinflammation is a hallmark of the Alzheimer’s disease (AD) pathogenic process. Cortisol dysregulation may increase AD risk and is related to brain atrophy. This cross-sectional study aims to examine interactions of cortisol patterns and neuroinflammation markers in their association with neuroimaging correlates. Method134 participants were recruited from the Karolinska University Hospital memory clinic (Stockholm, Sweden). Four visual rating scales were applied to magnetic resonance imaging or computed tomography scans: medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), white matter lesions (WML), and posterior atrophy. Participants provided saliva samples for assessment of diurnal cortisol patterns, and underwent lumbar punctures for cerebrospinal fluid (CSF) sampling. Three cortisol measures were used: the cortisol awakening response, total daily output, and the ratio of awakening to bedtime levels. Nineteen CSF neuroinflammation markers were categorized into five composite scores: proinflammatory cytokines, other cytokines, angiogenesis markers, vascular injury markers, and glial activation markers. Ordinal logistic regressions were conducted to assess associations between cortisol patterns, neuroinflammation scores, and visual rating scales, and interactions between cortisol patterns and neuroinflammation scores in relation to visual rating scales. ResultHigher levels of angiogenesis markers were associated with more severe WML. Some evidence was found for interactions between dysregulated diurnal cortisol patterns and greater neuroinflammation-related biomarkers in relation to more severe GCA and WML. No associations were found between cortisol patterns and visual rating scales. ConclusionThis study suggests an interplay between diurnal cortisol patterns and neuroinflammation in relation to brain structure. While this cross-sectional study does not provide information on causality or temporality, these findings suggest that neuroinflammation may be involved in the relationship between HPA-axis functioning and AD.

A Study of Factors Affecting Functional Outcomes in Patients With Successful Recanalization by Mechanical Thrombectomy.

Reperfusion therapy is typically performed in cases with acute cerebral infarction. Mechanical thrombectomy (MT) achieves superior recanalization and favorable outcomes. However, some patients have poor functional prognosis despite successful recanalization. We investigated factors affecting functional prognosis after MT with good reperfusion. Among the 205 consecutive cases with ischemic stroke treated with MT at our center from January 1, 2019 to March 31, 2021, 168 with successful recanalization were included. Factors affecting early neurological improvement (ENI) and modified Rankin Scale (mRS) scores were reviewed retrospectively. There were 93 (55%) cases with ENI and 75 (45%) without ENI. The times from onset to recombinant tissue-type plasminogen activator administration and recanalization in ENI cases were shorter than those in non-ENI cases. However, non-ENI cases had significantly higher Fazekas grades for white matter lesions. In multivariate analysis, the Fazekas grade was related to ENI (odds ratio [OR]=0.572, 95% confidence interval [CI]=0.345-0.948). The mRS score at discharge was 0-2 in 64 cases (good outcome) and 3-6 in 104 cases (poor outcome). Patients with a poor outcome had a significantly higher age, National Institutes of Health Stroke Scale (NIHSS) score, and Fazekas grade. Multivariate analysis revealed that the NIHSS score (OR=1.073, 95% CI=1.020-1.129) and Fazekas grade (OR=2.162, 95% CI=1.458-3.205) at hospitalization affected the mRS score at discharge. There is a correlation of greater severity of white matter lesions with poorer ENI and clinical outcomes at discharge post-MT.

Neurodevelopmental Outcome at 3 Years of Age in Very Low Birth Weight Infants According to Brain Development and Lesions.

During the last decades, severe brain lesions affecting very low birth weight (<1500 gr, VLBW) infants were gradually substituted by milder lesions with debatable prognoses. The objective of this study is to define type, frequency and 3 years of neurodevelopmental outcome of prematurity-related brain lesions in a modern cohort of VLBW infants. VLBW infants admitted to our NICU in 5 years period with brain MRI at term-equivalent age were included. MRI scans were reviewed to identify and grade white matter lesions (WML), intraventricular hemorrhage (IVH), and cerebellar hemorrhage (CBH). Linear measurements of brain size, biparietal width (BPW) and trans-cerebellar diameter (TCD) were carried out. Total maturation score (TMS) was calculated. Developmental Coefficients (DQ) on Griffiths Scale at 3 years of age were compared between patients with different types and grades of lesions and patients without lesions; possible correlations between linear brain measurements, brain maturation and outcome were explored. Study included 407 patients. Of them, 187 (46%) had at least one brain lesion on MRI, while 37 (9%) had severe lesions. The most frequent lesion was IVH (28%), followed by WML (21%) and CBH (17%). Mild and severe IVH, moderate and severe WML and all grades of CBH were related to worst outcome at 3 years. In patients without lesions, small BPW and small TCD were associated with worse outcomes. No correlations were observed between TMS and outcome. We have observed that even mild brain lesions have a negative influence on neurological outcome at 3 years of age.

Deep learning-based white matter lesion volume on CT is associated with outcome after acute ischemic stroke.

Intravenous thrombolysis (IVT) before endovascular treatment (EVT) for acute ischemic stroke might induce intracerebral hemorrhages which could negatively affect patient outcomes. Measuring white matter lesions size using deep learning (DL-WML) might help safely guide IVT administration. We aimed to develop, validate, and evaluate a DL-WML volume on CT compared to the Fazekas scale (WML-Faz) as a risk factor and IVT effect modifier in patients receiving EVT directly after IVT. We developed a deep-learning model for WML segmentation on CT and validated with internal and external test sets. In a post hoc analysis of the MR CLEAN No-IV trial, we associated DL-WML volume and WML-Faz with symptomatic-intracerebral hemorrhage (sICH) and 90-day functional outcome according to the modified Rankin Scale (mRS). We used multiplicative interaction terms between WML measures and IVT administration to evaluate IVT treatment effect modification. Regression models were used to report unadjusted and adjusted common odds ratios (cOR/acOR). In total, 516 patients from the MR CLEAN No-IV trial (male/female, 291/225; age median, 71 [IQR, 62-79]) were analyzed. Both DL-WML volume and WML-Faz are associated with sICH (DL-WML volume acOR, 1.78 [95%CI, 1.17; 2.70]; WML-Faz acOR, 1.53 95%CI [1.02; 2.31]) and mRS (DL-WML volume acOR, 0.70 [95%CI, 0.55; 0.87], WML-Faz acOR, 0.73 [95%CI 0.60; 0.88]). Only in the unadjusted IVT effect modification analysis WML-Faz was associated with more sICH if IVT was given (p= 0.046). Neither WML measure was associated with worse mRS if IVT was given. DL-WML volume and WML-Faz had a similar relationship with functional outcome and sICH. Although more sICH might occur in patients with more severe WML-Faz receiving IVT, no worse functional outcome was observed. White matter lesion severity on baseline CT in acute ischemic stroke patients has a similar predictive value if measured with deep learning or the Fazekas scale. Safe administration of intravenous thrombolysis using white matter lesion severity should be further studied. White matter damage is a predisposing risk factor for intracranial hemorrhage in patients with acute ischemic stroke but remains difficult to measure on CT. White matter lesion volume on CT measured with deep learning had a similar association with symptomatic intracerebral hemorrhages and worse functional outcome as the Fazekas scale. A patient-level meta-analysis is required to study the benefit of white matter lesion severity-based selection for intravenous thrombolysis before endovascular treatment.

Prenatal Opioid Exposure and Risk for Adverse Brain and Motor Outcomes in Infants Born Premature

ObjectiveTo compare brain MRI biomarkers and neurodevelopmental test scores in infants born preterm with and without prenatal opioid exposure (POE). Study designWe examined 395 preterm infants (≤ 32 weeks gestational age[GA]) who had term-equivalent brain MRIs, composite scores from the Bayley Scales of Infant and Toddler Development-III(BSID-III) at 2 years corrected age, and POE data. MRI parameters included total/regional brain volumes and severe punctate white matter lesions (PWMLs). We conducted bivariable analysis and multivariable logistic regression analyses. ResultsThe mean(SD) gestational age was 29.3(2.5) weeks; 35(8.9%) had POE and 20(5.1%) had severe PWML. Compared with unexposed infants, those with POE exhibited higher rates of severe PWML (17.1% vs. 3.9%, respectively; p=0.002); findings remained significant with OR 4.16 (95% CI:1.26, 13.68) after adjusting for confounders. On mediation analysis, the significant relationship between POE and severe PWML was not indirectly mediated through preterm birth/GA (OR:0.93; 95% CI:0.78,1.10), thus suggesting the association was largely driven by a direct adverse effect of POE on white matter. In multivariable analyses, POE was associated with a significantly lower score by -6.2 (95%CI: -11.8,-0.6) points on BSID-III Motor subscale compared with unexposed infants. ConclusionsPOE was associated with severe PWML; this outcome may be a direct effect of POE rather than being mediated by premature birth. POE was also associated with worse motor development. Continued follow-up to understand the long-term effects of POE is warranted.

Association between brain imaging biomarkers and continuous glucose monitoring-derived glycemic control indices in Japanese patients with type 2 diabetes mellitus

IntroductionAlthough type 2 diabetes mellitus (T2DM) is associated with alterations in brain structure, the relationship between glycemic control indices and brain imaging markers remains unclear. This study aimed to investigate...

Construction and validation of a nomogram model to predict symptomatic intracranial hemorrhage after intravenous thrombolysis in elderly population with severe white matter lesions

Background and Objective: Elderly people are at high prevalence of atherosclerotic cerebral infarction. Cerebral white matter lesions (WMLs) increase the risk of bleeding after intravenous thrombolysis (IVT) although they may also require the IVT. The aim of this study is to develop a clinical nomogram model for post-IVT symptomatic intracranial hemorrhage (sICH), with the aim to prevent sICH in elderly patients with severe WMLs when IVT is being considered. Methods: This is a large single-center retrospective analysis study of elderly patients with severe WMLs receiving IVT from January 2018 to December 2022. Univariate and multi-factor logistic regression analysis were used to construct nomogram model, and a series of validations were performed on the model. Results: More than 2,000 patients with IVT were screened for inclusion in this study after cranial magnetic resonance imaging evaluation. Out of these, 163 elderly patients had cerebral WMLs, and 25 had sICH. In univariate analysis, history of hypertension (p=0.037), hyperlipidemia (p&lt;0.001), NIHSS score before IVT (p&lt;0.001), low-density lipoprotein levels (p=0.016), cholesterol levels (p=0.020), platelet count (p=0.006), systolic blood pressure (p&lt;0.001), diastolic blood pressure (p&lt;0.001) were significantly associated with sICH. In a multifactorial analysis, the NIHSS score before IVT (OR 42.056 CI 7.308-242.012, p&lt;0.001), and diastolic blood pressure (OR 1.050 CI 1.002-1.100, p=0.040) were found to be significantly associated with sICH after IVT. The four most significant risk factors from logistic regression are subsequently fitted to create a predictive model. The accuracy was verified using calibration curves, decision curves, and clinical impact curves, and the model was considered to have strong stability. Conclusions: The NHISS score before IVT and diastolic blood pressure are independent risk factors for sICH after IVT in elderly patients with severe WMLs. The models are highly accurate and can be applied clinically to provide a reliable predictive basis for IVT in elderly patients with severe WMLs.

Diurnal cortisol, neuroinflammation, and neuroimaging visual rating scales in memory clinic patients

AbstractBackgroundNeuroinflammation is considered a hallmark of the Alzheimer’s disease (AD) pathogenic process. Dysregulations in stress hormones (cortisol) may increase AD risk and are related to brain atrophy. This cross‐sectional study aims to examine interactions of cortisol patterns and neuroinflammation markers in their association with neuroimaging correlates.Method188 participants were recruited from the Karolinska University Hospital memory clinic (Stockholm, Sweden), and underwent magnetic resonance imaging or computed tomography. Four visual rating scales were applied to the scans: medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), white matter lesions (Fazekas), and posterior atrophy (Koedam). Additionally, participants provided saliva to assess diurnal cortisol patterns, and underwent lumbar punctures for cerebrospinal fluid (CSF) sampling. Five cortisol measures were used: awakening levels, bedtime levels, cortisol awakening response (CAR), total daily output, and the ratio of awakening to bedtime levels (AM/PM ratio). Nineteen CSF neuroinflammation markers were categorized into five composite scores (mean z‐scores): proinflammatory cytokines (Interleukin (IL‐)6, IL‐8, IL‐15, IL‐12/IL‐23 p40, CC chemokine ligand (CCL)4, CXC chemokine ligand 10), other cytokines (IL‐5, IL‐16, CCL17), angiogenesis markers (Vascular endothelial growth factor (VEGF), VEGF‐D, VEGF‐receptor 1, Placental growth factor), vascular injury markers (Serum amyloid A, C‐reactive protein, Vascular cell adhesion molecule‐1, Intercellular adhesion molecule‐1), and glial activation markers (YKL‐40, CCL2). Ordinal logistic regressions were conducted to assess associations between cortisol patterns, neuroinflammation scores, and visual rating scales, and interactions between cortisol patterns and neuroinflammation composite scores in predicting visual rating scales.ResultHigher levels of angiogenesis markers were associated with greater odds of more severe white matter lesions. Furthermore, awakening cortisol levels, bedtime levels, CAR, and total daily output independently interacted with ‘other cytokines’ scores to predict MTA, CAR and total daily output independently interacted with ‘proinflammatory cytokines’ scores to predict white matter lesions, and the AM/PM ratio interacted with angiogenesis markers to predict GCA. No associations were found between cortisol patterns and visual rating scales.ConclusionThis study provides evidence for potential interplay between diurnal cortisol patterns and neuroinflammation. While this study does not provide information on causality, these findings suggest that neuroinflammation is involved in the pathway between chronic stress and AD.

Higher High-Mobility Group Box-1 Levels are Associated with White Matter Lesions in Ischemic Stroke Patients.

High-mobility group box-1 (HMGB1) is a useful biomarker for disease severity stratification and prognosis prediction. We aim to explore whether the circulating HMGB1 concentrations are associated with the white matter lesions (WMLs) burden in stroke patients. Between 2022 June and December 2022, patients with acute ischemic stroke were prospectively enrolled. HMGB1 levels were measured by an enzyme-linked immunosorbent assay after admission for all patients. The WMLs severity was assessed by the Fazekas scale. We dichotomized patients into those with moderate-severe WMLs (Fazekas score 3-6) versus those with none-mild WMLs (Fazekas score 0-2). Furthermore, based on the severity of periventricular WMLs (PWMLs) and deep WMLs (DWMLs), patients were categorized as none-mild (Fazekas score 0-1) or moderate-severe (Fazekas score 2-3). A total of 287 participants (mean age: 64.9 years; 157 male) were analyzed. The median serum HMGB1 levels were 7.3 ng/mL (interquartile, 4.3 ng/mL-12.3 ng/mL). After adjustment for potential confounders, elevated HMGB1 levels were associated with the presence of moderate-severe WMLs (first quartile vs fourth quartile, odds ratio [OR], 4.101; 95% confidence interval [CI], 1.948-8.633; P = 0.001) and moderate-severe PWMLs (first quartile vs fourth quartile, OR, 9.181; 95% CI, 4.078-20.671; P = 0.001). Similar results were found when the HMGB1 levels were analyzed as a continuous variable. This study demonstrated that increased HMGB1 levels were associated with the severity of WMLs, mainly in the periventricular region.

Predicting the severity of white matter lesions among patients with cerebrovascular risk factors based on retinal images and clinical laboratory data: a deep learning study.

As one common feature of cerebral small vascular disease (cSVD), white matter lesions (WMLs) could lead to reduction in brain function. Using a convenient, cheap, and non-intrusive method to detect WMLs could substantially benefit to patient management in the community screening, especially in the settings of availability or contraindication of magnetic resonance imaging (MRI). Therefore, this study aimed to develop a useful model to incorporate clinical laboratory data and retinal images using deep learning models to predict the severity of WMLs. Two hundred fifty-nine patients with any kind of neurological diseases were enrolled in our study. Demographic data, retinal images, MRI, and laboratory data were collected for the patients. The patients were assigned to the absent/mild and moderate-severe WMLs groups according to Fazekas scoring system. Retinal images were acquired by fundus photography. A ResNet deep learning framework was used to analyze the retinal images. A clinical-laboratory signature was generated from laboratory data. Two prediction models, a combined model including demographic data, the clinical-laboratory signature, and the retinal images and a clinical model including only demographic data and the clinical-laboratory signature, were developed to predict the severity of WMLs. Approximately one-quarter of the patients (25.6%) had moderate-severe WMLs. The left and right retinal images predicted moderate-severe WMLs with area under the curves (AUCs) of 0.73 and 0.94. The clinical-laboratory signature predicted moderate-severe WMLs with an AUC of 0.73. The combined model showed good performance in predicting moderate-severe WMLs with an AUC of 0.95, while the clinical model predicted moderate-severe WMLs with an AUC of 0.78. Combined with retinal images from conventional fundus photography and clinical laboratory data are reliable and convenient approach to predict the severity of WMLs and are helpful for the management and follow-up of WMLs patients.

Association between Citrullinated Histone H3 and White Matter Lesions Burden in Patients with Ischemic Stroke.

Neutrophil extracellular traps play a role in the pathophysiology of stroke and are associated with severity and mortality. We aimed to investigate whether the citrullinated histone H3 (CitH3), a biomarker for neutrophil extracellular traps formation, is associated with the white matter lesion (WML) burden in ischemic stroke patients. Between September 2021 and April 2022, 322 patients were enrolled in this prospective observational cohort study. Serum CitH3 levels were measured after admission using an enzyme-linked immunosorbent assay. WMLs severity was graded according to the Fazekas scale and conceptually defined as mild (total Fazekas score 0-2) and severe (total Fazekas score 3-6). We used multivariable regression models to determine the relationship between CitH3 concentrations and the severity of WMLs burden. One-hundred and forty-eight (46.0%) patients were diagnosed with severe WMLs burden after admission. Increased CitH3 levels (first quartile vs. fourth quartile of H3Cit, odds ratio, 3.311, 95% confidence interval, 1.336-8.027; p = 0.011) were independently associated with a greater WML burden in the fully adjusted multivariable model. Similar results were found when the H3Cit was analyzed as a continuous variable. Furthermore, the multiple-adjusted spline regression model showed a linear association between H3Cit levels and severe WMLs (P = 0.001 for linearity). In the present study, increased CitH3 levels were positively associated with extensive WMLs in ischemic stroke patients, indicating a role of neutrophil extracellular traps formation in the pathogenesis of WMLs.

Microbial lipopolysaccharide-induced inflammation contributes to cognitive impairment and white matter lesion progression in diet-induced obese mice with chronic cerebral hypoperfusion.

White matter lesions (WMLs) are involved in the pathological processes leading to cognitive decline and dementia. We examined the mechanisms underlying the exacerbation of ischemia-induced cognitive impairment and WMLs by diet-induced obesity, including lipopolysaccharide (LPS)-triggered neuroinflammation via toll-like receptor (TLR) 4. Wild-type (WT) and TLR4-knockout (KO) C57BL/6 mice were fed a high-fat diet (HFD) or low-fat diet (LFD), and subjected to bilateral carotid artery stenosis (BCAS). Diet groups were compared for changes in gut microbiota, intestinal permeability, systemic inflammation, neuroinflammation, WML severity, and cognitive dysfunction. In WT mice, HFD induced obesity and increased cognitive impairment and WML severity compared with LFD-fed mice following BCAS. HFD caused gut dysbiosis and increased intestinal permeability, and plasma LPS and pro-inflammatory cytokine concentrations. Furthermore, HFD-fed mice had higher LPS levels and higher neuroinflammatory status, including increased TLR4 expression, in WMLs. In TLR4-KO mice, HFD also caused obesity and gut dysbiosis but did not increase cognitive impairment or WML severity after BCAS. No difference was found between HFD- and LFD-fed KO mice for LPS levels or inflammatory status in either plasma or WMLs. Inflammation triggered by LPS-TLR4 signaling may mediate obesity-associated exacerbation of cognitive impairment and WMLs from brain ischemia.

Correlation of White Matter Lesions Severity and Age in Ischemic Stroke at Siloam Jember Hospital

White matter lesions is a disease that is often found in stroke patients and is associated with an increased risk of stroke. In addition, WML is often referred to as a degenerative disease. Stroke is one of the diseases with a high prevalence in Indonesia, including in East Java. Stroke is also often associated with increased age. The most common cause of stroke is due to ischemia in the brain. The research conducted was observational analytical research with a cross-sectional research design. The data used in the study was a medical record of magnetic resonance imaging (MRI) examination. WML severity degrees are differentiated using the Fazekas scale. The study was conducted on 60 samples. The results showed a significant and positive relationship with a p-value of 0.016 and a correlation coefficient of 0.31. From the results of the study, it can be concluded that there is a relationship between the severity of WML and increased age in chronic stroke patients at Siloam Hospital Jember with the strength of the relationship between the two variables is weak.&#x0D; &#x0D; Keywords : White Matter Lesions, Ischemic Stroke, Age, MRI, Fazekas&#x0D; Correspondence : fatmawatiheni@unej.ac.id

Construction and validation of a nomogram model to predict symptomatic intracranial hemorrhage after intravenous thrombolysis in severe white matter lesions.

Cerebral white matter lesions (WMLs) increase the risk of bleeding after intravenous thrombolysis (IVT) but are also considered to require IVT. Its risk factors and predictive models are still poorly studied. The aim of this study is to develop a clinically applicable model for post-IVT haemorrhage. It offers the possibility to prevent symptomatic intracranial hemorrhage (sICH) in patients with IVT in severe WMLs. A large single-center observational study conducted a retrospective analysis of IVT in patients with severe WMLs from January 2018 to December 2022. Univariate and multi-factor logistic regression results were used to construct nomogram model, and a series of validations were performed on the model. More than 2,000 patients with IVT were screened for inclusion in this study after cranial magnetic resonance imaging evaluation of 180 patients with severe WMLs, 28 of whom developed sICH. In univariate analysis, history of hypertension (OR 3.505 CI 2.257-4.752, p = 0.049), hyperlipidemia (OR 4.622 CI 3.761- 5.483, p < 0.001), the NIHSS score before IVT (OR 41.250 CI 39.212-43.288, p < 0.001), low-density lipoprotein levels (OR 1.995 CI 1.448-2.543, p = 0.013), cholesterol levels (OR 1.668 CI 1.246-2.090, p = 0.017), platelet count (OR 0.992 CI 0.985-0.999, p = 0.028), systolic blood pressure (OR 1.044 CI 1.022-1.066, p < 0.001), diastolic blood pressure (OR 1.047 CI 1.024-1.070, p < 0.001) were significantly associated with sICH. In a multifactorial analysis, the NIHSS score before IVT (OR 94.743 CI 92.311-97.175, p < 0.001), and diastolic blood pressure (OR 1.051 CI 1.005-1.097, p = 0.033) were considered to be significantly associated with sICH after IVT as risk factors for the occurrence of sICH. The four most significant factors from logistic regression are subsequently fitted to create a predictive model. The accuracy was verified using ROC curves, calibration curves, decision curves, and clinical impact curves, and the model was considered to have high accuracy (AUC 0.932, 95% 0.888-0.976). The NHISS score before IVT and diastolic blood pressure are independent risk factors for sICH after IVT in patients with severe WMLs. The models based on hyperlipidemia, the NIHSS score before IVT, low-density lipoprotein and diastolic blood pressure are highly accurate and can be applied clinically to provide a reliable predictive basis for IVT in patients with severe WMLs.

White matter disease and recovery following endovascular thrombectomy after acute ischemic stroke (P11-5.006)

<h3>Objective:</h3> To determine the impact of chronic white matter lesions (WML) on functional outcomes in patients with acute stroke who underwent endovascular thrombectomy (EVT). <h3>Background:</h3> The evidence regarding the impact of chronic WML on functional outcomes after EVT is mixed. <h3>Design/Methods:</h3> A prospective stroke center registry (10/2019–06/2021) of consecutive adult patients with acute stroke was queried for patients with ICA or M1 occlusions who had undergone magnetic resonance imaging (MRI). Multivariable logistic regression was used to estimate the relationship between age, Alberta Stroke Program Early Computed Tomography Scale score, National Institutes of Health Stroke Scale, occlusion location, and successful recanalization (thrombolysis in cerebral infarction score of 2b–3 versus 0–2a or no thrombectomy) on good functional outcome (90-day mRS 0–2). Mediation analysis was used to estimate the effect of WML severity on age as a predictor of good functional outcome following successful recanalization. <h3>Results:</h3> Among the 121 included patients, the median age was 67y (IQR 58–77), 49 (40.5%) were female, and 39 (32.2%) had a Fazekas score of 2 or 3. In unadjusted regression, age was associated with WML severity (step 1: OR 1.03, 95% CI 1.02–1.04, p&lt;0.001), and age was associated with an unfavorable 90-day mRS (step 2: proportional OR 0.98, 95% CI 0.95–0.99, p = 0.027). WML severity was also associated with 90-day mRS (step 3: OR 0.74, 95% CI 0.52–1.06, p=0.096). In multivariable regression, the total effect of age on unfavorable shift in 90-day mRS remained significant (OR 0.96, 95% CI 0.94–0.98, p&lt;0.001), with a trend toward a persistent indirect mediator effect of WML (p=0.084). The mediator WML severity explained 23% of the association of age with 90-day mRS. <h3>Conclusions:</h3> In this single center analysis, WML burden partially mediated the effect of age on functional recovery in acute stroke. <b>Disclosure:</b> Mr. Vigilante has nothing to disclose. Ms. Koneru has nothing to disclose. Ms. Penckofer has nothing to disclose. Mr. Sprankle has nothing to disclose. Dr. Patel has nothing to disclose. Dr. Khalife has nothing to disclose. Dr. Oliveira has nothing to disclose. Scott Kamen has nothing to disclose. An immediate family member of Dr. Thon has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. An immediate family member of Dr. Thon has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. An immediate family member of Dr. Thon has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genentech. Dr. Thon has received personal compensation in the range of $500-$4,999 for serving as a Focus group participant with Alexion. Dr. Siegler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Ceribell. Dr. Siegler has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for AstraZeneca.

Whether jugular venous reflux relates to more serious ischemic white matter lesions?

ObjectiveTo evaluate whether jugular venous reflux (JVR) relates to more serious ischemic white matter lesions (WMLs). Patients and MethodsFifty cases were enrolled and divided into absent to mild ischemic WMLs group and moderate to severe ischemic WMLs group. Then the univariate and multivariate analyses were conducted to evaluate the relationship between JVR and moderate to severe ischemic WMLs, and a receiver operating characteristic (ROC) curve was used to evaluate the predictive value of JVR for moderate to severe ischemic WMLs. ResultsThere were 28 patients in the absent to mild ischemic WMLs group and 22 patients in the moderate to severe ischemic WMLs group. There was no significant difference between the two groups in gender, blood lipid indexes, proportions of diabetes, and abnormal deep cerebral veins (all p > 0.05). However, compared with the absent to mild ischemic WMLs group, the moderate to severe ischemic WMLs group was older and had a higher proportion of hypertension and JVR (p = 0.005; p < 0.001; p < 0.001, respectively). Multivariate logistic regression analysis showed that JVR was an independent risk factor for moderate to severe ischemic WMLs (OR = 17.679, 95 % CI: 3.056–102.286, p = 0.001). Furthermore, the area under curve of JVR combined with hypertension was 0.912 (p < 0.001), and the specificity of predicting moderate to severe ischemic WMLs was 92.9 %. ConclusionOur study suggested that JVR might relate to more severe ischemic WMLs.

S-35-3: HAMA, AN EUROPEAN REGISTRY OF MALIGNANT HYPERTENSION SUPPORTED BY THE EUROPEAN SOCIETY OF HYPERTENSION: PRELIMINARY RESULTS AND CURRENT PERSPECTIVES

Introduction: Malignant hypertension (MH) is one of the most severe acute forms of hypertension. It is very high blood pressure and an acute lesion of target organ damage. Incidence is currently increased in high-income countries and is higher in low-income countries due to difficulty with antihypertensive drug access. Causes of MH are very various, and probably prognosis of MH depends on the etiology. However, MH is not well known. We are conducting a multicentric prospective registry of MH patients started in 2019, primarily in France and is currently undergoing a European expansion with the support of the European Society of Hypertension (ESH) to describe the different forms and prognosis of MH and increase our knowledge of the disease (NCT03755726). Method: From 2019, in the 36 centres in France, Patients with a BP &gt; 180/100 mmHg AND Severe Hypertensive Retinopathy - stade II or III of Kirkendall classification - OR with three criteria among the following: 1) Heart damage (Left ventricular Mass &gt; 140 g/m2 for men of &gt; 120 g/m2 for women); 2) Brain damage (PRES or acute stroke or severe white matter lesions (WML) with a Fazekas score &gt; 2 before 60 years old); 3) Kidney damage (acute kidney injury defined by KDIGO criteria) 4) presence of Thrombotic Microangiopathy (TMA) with the presence of schizocytes and low haptoglobin or high LDH) were included. Results: To date, 278 patients were enrolled. The reason for hospital admission was symptomatic hypertension for 210/272 (77%) and asymptomatic hypertension for 62/272 (23%) BP was 218 ± 28 / 127 ± 23 mmHg. The mean age was 48 ± 15 years old. Males were 186/278 (67%). Non-Caucasians were 114/278 (41%), 101/278 (36%) smoked and 45/278 (16%) had diabetes. Before enrollment, 108/278 (39%) patients had chronic hypertension. Severe retinopathy was present in 251/278 (90%), Heart damage in 172/278 (62%), kidney damage in 176/278 (63%), and creatinine was 261 ± 326 μmol/l at admission. Brain damage was present in 105/278 (38%), 47/105 (45%) patients had severe WML. TMA was present in 40/278 (14%) patients. At discharge, BP was 148 ± 19 / 89 ± 15 mmHg; creatinine was 248 ± 274 μmol/l. The etiology of hypertension was assessed in 181/278 (65%), and a specific cause was found in 75/181 (41%). Conclusion: This multicentric prospective cohort is the opportunity to considerably increase our knowledge of MH, a non-uncommon severe disease. A biobank is currently being started to identify patients clustering to differentiate the etiology, prognosis and pathogenesis of each form of MH.

The role of the fibrinolytic system laboratory markers in the assessment of the cerebral small vessel disease severity

Background: Small vessel disease (SVD) is a common brain disease causing about 40% of all dementias and about 25% of ischemic strokes, which makes important the study of its pathophysiology and the search for its biomarkers. A number of studies have shown a significant role of endothelial dysfunction and nonspecific inflammation, as well as of some individual parameters of hemostasis disorders in the development of SVD.&#x0D; Aim: To identify the role of the laboratory markers of fibrinolytic system in the assessment of the severity of white matter lesions in patients with SVD.&#x0D; Materials and methods: This single center cross-sectional non-controlled observational study included 117 patients with dyscirculatory encephalopathy (chronic brain ischemia), with a mean ( SD) age of 57.7 11.5 years. Laboratory tests of the fibrinolytic system, endothelial dysfunction, markers of inflammation and for an integral assessment of plasma hemostasis were performed in all patients, including XIIa-dependent fibrinolysis, levels of plasminogen, alpha2-antiplasmin, plasminogen activator inhibitor 1 (PAI-1), fibrinogen, von Willebrand factor (vWF) and activity of blood coagulation factor VIII (FVIII), highly sensitive C-reactive protein and parameters of the thrombodynamics assay. In all the patients, brain magnetic resonance imaging was performed with the assessment of the white matter lesions by the Fazecas scale.&#x0D; Results: Depending on the identified neuroimaging SVD markers (assessed with the Fazecas scale), the patients were divided into the SVD group (n = 54) and no-SVD group (n = 63). Those with SVD were older than those without (65 9 vs 51 10 years; p 0.001), had higher prevalence of arterial hypertension (p 0.001), diabetes mellitus (p = 0.029) and past thrombotic events (p 0.001). The SVD patients, compared to those without SVD, had a higher time of XIIa-dependent fibrinolysis (7.6 2.9 vs 6.5 1.7 min, p = 0.032), higher alpha2-antiplasmin levels (111 [95117] vs 105 [95111]%, p = 0.016) and higher clot density (D) (22789 [2056726411] vs 20627 [1832422650] U, p 0.001), although the parameters were within the reference ranges. As far as the thrombodynamics is concerned, the SVD group had higher values for all test parameters, as well as higher levels of the inflammation and endothelial dysfunction markers. Increased time of XIIa-dependent fibrinolysis was associated with higher probability of periventricular and subcortical leukoareosis grade 2 by the Fazecas scale (odds ratio 1.31 [1.071.60], p = 0.009), including an increase in the size and number of gliosis areas. Higher plasminogen levels were associated with a lower probability of leukoareosis by the Fazecas scale (odds ratio 0.97 [0.950.98], p 0.001).&#x0D; Conclusion: The severity of fibrinolytic and hemostatic abnormalities correlates with the severity of brain SVD, thus forming the hypofibrinolytic and prothrombotic status of the patients with this disorder.