Fazekas Score Research Articles

Association of white matter hyperintensities with lipoprotein (a) levels: insights from a cohort study

BackgroundLittle is known about the relationship between lipoprotein (a) [Lp(a)] and cerebral white matter hyperintensities (WMH). The aim of the study was to examine if elevated Lp(a) levels are associated with higher burden of WMH.MethodsWe retrospectively investigated associations between Lp(a) and the burden of WMH among patients with confirmed diagnosis of acute ischemic stroke or transient ischemic attacks. WMH burden was assessed using 3-Tesla brain MRI and graded according to the Fazekas score. Multivariable models were generated to determine the contribution of Lp(a) to the presence and extent of WMH.ResultsOne hundred and fifty-three patients were included (mean age, 45.9 years; 35.9% women). When the study population was stratified by Lp(a) level into three categories, low (<75 nmol/L), moderate (75 to <125 nmol/L), and high (≥125 nmol/L), the distribution of the three groups was 60.8, 15.0 and 24.2%, respectively. High Lp(a) Level was associated with higher burden of both periventricular WMH and deep WMH compared to the lower level (odds ratio [OR], 4.4; 95% confidence interval [CI], 1.60–12.07; p = 0.004; and OR, 5.6; CI, 1.69–14.7; p = 0.001, respectively).ConclusionWe show in this cohort of patients that a higher burden of WMH was observed in patients with higher level of Lp(a). Further studies are needed to confirm this observation and assess whether lowering Lp(a) level may be a potential therapeutic target for mitigating the development of WMH.

Short- and Long-Term Prognoses After Tissue-Negative Transient Ischemic Attack.

The tissue-based definition of transient ischemic attack, which requires the use of diffusion-weighted imaging (DWI), has limitations in its applicability to clinical practice. This contributes to the limited evidence regarding the risk of subsequent stroke and the associated predictors in the group of patients who are tissue-negative on DWI. Our aim was to assess the early and long-term prognoses of consecutive patients with tissue-negative transient ischemic attacks attended at an emergency department. We performed a prospective cohort study of consecutive patients with neurologist-confirmed transient ischemic attack who were DWI-negative from January 2006 to June 2010. All patients underwent DWI on magnetic resonance imaging (4.0 [SD, 1.8] days) after the index event. The risk and predictors of stroke recurrence (SR) were determined at 1 year and after a median follow-up time of 6.6 (interquartile range, 5.0-9.6) years. A total of 370 patients were included. Previously, 244 patients with positive DWI results and 109 patients without magnetic resonance imaging performed were excluded. ABCD2 score >5 was determined in 95 (26.2%) patients; 15 (4.1%) patients experienced SR at 1 year and 18 (4.9%) beyond 1 year. Predictive models for short- and long-term prognoses were different. Large artery atherosclerosis cause (hazard ratio, 3.7 [95% CI, 1.2-11.0]) was the only predictor of 1-year SR. In contrast, male sex (hazard ratio, 4.17 [95% CI, 1.14-15.23]; P=0.031), speech impairment (hazard ratio, 4.90 [95% CI, 1.05-22.93]; P=0.044), and the presence of chronic microangiopathy expressed as Fazekas score of 3 (hazard ratio, 1.84 [95% CI, 1.15-2.97]; P=0.012) were predictors of long-term SR follow-up. Patients with DWI-negative have a clinically important risk of recurrent vascular events and SR during medium- and long-term follow-ups. These patients warrant optimized secondary prevention to reduce their risk of recurrent vascular events over time. Predictors of SR varied over the follow-up.

Association between plasma trimethylamine N-oxide and cerebral white matter hyperintensity: a cross-sectional study.

Cerebral white matter hyperintensity (WMH) is a pivotal imaging feature of cerebral small vessel disease (CSVD), closely correlated with an elevated risk of ischemic stroke (IS). Trimethylamine N-oxide (TMAO), a metabolite of gut microbiota, is increasingly associated with IS and atherosclerosis. However, the intricate relationship between TMAO and WMH remains ambiguous. This study aimed to study the connection between plasma TMAO and WMH. Furthermore, it assessed the potential of TMAO as a risk evaluation instrument for WMH. In this cross-sectional study, we categorized WMH into periventricular WMH (P-WMH) and deep WMH (D-WMH), based on its locations. The severity of WMH was assessed and grouped according to the Fazekas scale. Plasma TMAO levels were quantitatively determined. We established the correlation between plasma TMAO levels and WMH severity using a Logistic regression model. Additionally, we employed ROC curves to evaluate the diagnostic efficacy of plasma TMAO concentration in distinguishing the severity of WMH. A higher plasma TMAO tertile was significantly linked to a higher Fazekas score, encompassing the overall score, P-WMH score, and D-WMH score (p < 0.001). A logical regression analysis revealed that plasma TMAO levels were independently associated with overall moderate and severe WMH, compared to overall non-mild WMH, in the unadjusted model (OR = 1.373, 95%CI 1.183-1.594 for moderate; OR = 1.384, 95%CI 1.192-1.607 for severe), the adjusted model a (OR = 1.436, 95%CI 1.214-1.669 for moderate; OR = 1.446, 95%CI 1.222-1.711 for severe) and the adjusted model b (OR = 1.490, 95%CI 1.234-1.800 for moderate; OR = 1.494, 95%CI 1.237-1.805 for severe). The analysis also showed an independent correlation between plasma TMAO levels and WMH severity, irrespective of the unadjusted model, adjusted model a, or adjusted model b, when considering P-WMH and D-WMH severity. The ROC indicated that, in overall WMH and P-WMH, the area under curve (AUC) for non-mild and severe WMH were both>0.5, while the AUC for moderate WMH was<0.5. In contrast, in D-WMH, the AUC for non-mild, moderate, and severe WMH were all>0.5. Plasma TMAO levels exhibited a significant correlation with both overall and region-specific WMH severity. Furthermore, the plasma TMAO levels displayed robust predictive capability for D-WMH.

Prevalence and Clinical Implications of Hemosiderin Deposits in Recent Small Subcortical Infarcts.

A quarter of ischemic strokes are of lacunar clinical subtype and have an underlying recent small subcortical infarct (RSSI), but their long-term outcomes remain poorly characterized. Hemosiderin deposits (HDs) have been noted in RSSIs at chronic stages and might mimic primary hemorrhage. We characterized HDs' morphology, frequency, and clinical relevance. Participants with RSSIs were identified from a prospective longitudinal study and evaluated on 3T MRI including susceptibility-weighted imaging (SWI) from stroke diagnosis to 12 months. We categorized HDs in RSSIs on SWI at all available time points into 4 types (spots, smudge, rim, cluster) and assessed their associations with demographic factors, stroke-related factors, and image markers with adjusted logistic regression. HDs were observed in 43 (55.0%) of 108 participants within 3 months and 83 (76.9%) of 108 within 12 months after stroke onset. The mean time to first detection of HDs was 87 (interquartile range 53-164) days. A "rim" pattern (similar to late appearance of primary hemorrhage) occurred in at least 26.5% of RSSIs at all follow-up time points, mainly those located in the lentiform/internal capsule (50.0%) or thalamus (36.4%). Infarct volume (odds ratio [OR] 1.003, 95% CI 1.001-1.006; p = 0.004) and the total small vessel disease (SVD) score at baseline (OR 2.50, 95% CI 1.28-4.86, p = 0.007) independently predicted HDs at 12 months. HDs were positively associated with more lacunes (OR 1.60, 95% CI 1.13-2.26, p < 0.01), but not the Fazekas score, number of microbleeds, basal ganglia mineral deposit score, or clinical outcomes. HDs occur commonly in RSSIs and may be associated with infarct volume and SVD score. Hemosiderin "rim" is common in RSSIs, urging caution to avoid mistaking ischemic RSSI for primary hemorrhage in subacute and chronic stages.

Alkaline phosphatase is associated with vascular depression in patients with severe white matter hyperintensities.

Cerebrovascular disease (CVD) poses a substantial risk for depression. Elevated levels of alkaline phosphatase (ALP) serve not only as an independent predictive factor for acute cerebrovascular events and unfavorable prognoses but also as a significant predictor of depression in premenopausal women. Nevertheless, the association between elevated ALP levels and vascular depression (VDe) in patients presenting with white matter hyperintensities (WMHs) remains unclear. In a cross-sectional survey, 265 individuals diagnosed with CVD were incorporated. Baseline demographic information, fasting blood parameters, and MRI data were systematically gathered for analysis. All patients were divided into a severe WMHs (sWMHs) group and a mild WMHs (mWMHs) group based on their Fazekas score. Univariate analysis of potential variables among different subgroups of patients with scores of Hamilton Rating Scale for Depression (HAMD) was performed. Subsequently, the diagnostic effectiveness of multivariables for positive VDe within two WMHs groups was assessed using binary logistic regression. The diagnostic capability of the multivariate approach for VDe was further scrutinized through ordinal logistic regression. (1) Hypersensitivity C-reactive protein (hs-CRP, p = 0.031), high-density lipoprotein cholesterol (HDL-C, p = 0.038), apolipoprotein A1 (APOA1, p = 0.009), and ALP (p = 0.011) exhibited distinct expression in patients with mWMHs across varying HAMD scores. In contrast, erythrocyte counts (p = 0.024), hemoglobin (Hb, p = 0.011), hs-CRP (p = 0.002), and ALP (p = 0.021) displayed differential expression in patients with sWMHs across different HAMD scores. (2) ALP and hs-CRP combined with APOA1 or Hb can improve the diagnostic efficiency of positive VDe in sWMHs [AUC = 0.849, 95% CI (0.753, 0.946), p < 0.001] or mWMHs [AUC = 0.718, 95% CI (0.603, 0.834), p = 0.002] patients, respectively. (3) Alkaline phosphatase (ALP) [OR = 1.016, 95% CI (1.003, 1.028), p = 0.016] is correlated with VDe in patients with sWMHs, a relationship that persisted even following adjustments for age and sex. The amalgamation of multiple markers enhances the diagnostic efficacy of VDe through WMHs classification. Serum ALP is associated with VDe in sWMHs patients.

Retinal vascular alterations are associated with cognitive function and neuroimaging in white matter hyperintensities

AimTo reveal alterations in retinal structure, vessels, and function, and their association with cognitive function and neuroimaging in white matter hyperintensities (WMH). MethodsThis study enlisted WMH and age-matched healthy controls (HC). All participants underwent six different tests: magnetic resonance imaging (MRI) of the brain, the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), fundus photography, optical coherence tomography (OCT), and visual field testing. Visual field can reflect the function of optic nerve and retina. The peripapillary retinal nerve fiber layer (p-RNFL) was analyzed using OCT. Image J software was employed to measure retinal vascular caliber in fundus photographs and to compute the central retinal artery equivalent (CRAE), central retinal venous equivalent (CRVE) and arteriole-to-venule ratio (AVR). ResultsA total of 90 WMH patients and 93 HC participants. In comparison with the HC, the WMH group exhibited reduced cognitive function scores (MoCA: P < 0.001; MMSE: P < 0.001), narrower retinal arteries (P < 0.001), smaller AVR (P < 0.001) and thinner p-RNFL thickness (total: P = 0.026; temporal: P = 0.006). About visual field, both univariate and multivariate analysis showed that mean sensitivity decreased, and mean defect increased in WMH group (P < 0.05). Additionally, correlation analysis indicated a positive correlation between CRAE and AVR with MMSE and MoCA score (r = 0.424–0.57, P < 0.001) and a negative correlation with Fazekas score (CRAE: r = −0.515, P < 0.001; AVR: r = −0.554, P < 0.001), and p-RNFL was negatively correlated with Fazekas score (total p-RNFL: r = −0.192, P = 0.009; temporal p-RNFL: r = −0.217, P = 0.003). Notably, no significant correlation was found between cognitive function and p-RNFL. ConclusionWMH group exhibit narrower retinal arteries, smaller arteriole-to-venule ratio, damaged p-RNFL and visual function. These alterations in retinal vessels are associate with both neuroimaging and cognitive function. Our results suggest that retinal imaging could serve as a valuable instrument for evaluating WMH and provides some new approaches to study the characteristic markers of WMH.

Amyloid-Related Imaging Abnormalities in Clinical Trials of Gantenerumab in Early Alzheimer Disease

Data from 2 phase 3 studies of gantenerumab, GRADUATE I/II, and their open-label extensions represent a resource to further characterize amyloid-related imaging abnormalities (ARIA), including long-term sequelae. To describe the characteristics of ARIA and risk factors and clinical consequences of ARIA-edema (ARIA-E). Secondary data collection from the GRADUATE I/II phase 3 randomized, double-blind, placebo-controlled, 116-week parallel-group studies and their open-label extensions, including PostGraduate, with up to 210 (mean, 125) weeks of total gantenerumab treatment were conducted between 2018 and 2023. The study included multicenter trials at 288 sites across 30 countries. GRADUATE I/II enrolled 985 and 980 participants, respectively, with early symptomatic Alzheimer disease (AD) and amyloid-beta (Aβ) pathology who were aged 50 to 90 years. PostGraduate enrolled 1382 participants (671 previously randomized to gantenerumab). Data were analyzed from November 2, 2022, to October 10, 2023. GRADUATE I/II participants were randomized 1:1 to gantenerumab or placebo. Nine-month uptitration was used to mitigate ARIA risk. Postbaseline safety monitoring, including brain magnetic resonance imaging (MRI) findings, and adverse events and cognitive assessments. The safety-evaluable MRI population of GRADUATE I/II comprised 1939 participants (mean age, 71.7 years; 1105 female [57.0%]). Severity of AD-related Aβ neuropathology (lower cerebrospinal fluid [CSF] Aβ42, hazard ratio [HR] for CSF Aβ42: 0.4; 95% CI, 0.2-0.7) and comorbid cerebrovascular pathology (Fazekas score: HR, 1.6; 95% CI, 1.3-2.0; total superficial siderosis count: HR, 1.9; 95% CI, 1.3-2.6; total microhemorrhage count: HR, 1.3; 95% CI, 1.0-1.5) may be important baseline risk factors for ARIA-E, in addition to apolipoprotein E (APOE) ε4 status (APOE ε4 heterozygous carrier: HR, 2.0; 95% CI, 1.4-2.8 and APOE ε4 homozygous carrier: HR, 4.7; 95% CI, 3.2-6.7). At the group level, ARIA-E did not impact long-term cognitive and functional performance (relative difference in adjusted means for Clinical Dementia Rating-Sum of Boxes was -9% in pooled GRADUATE analysis at week 116 and when censored at first ARIA-E). While taking gantenerumab, ARIA-E and ARIA-hemosiderin occurred in 24.9% (247 of 993) and 22.9% (227 of 993) participants, respectively; first ARIA-E occurred by week 64 in 86.2% (213 of 247) of participants with ARIA-E. Narratives are provided for all serious symptomatic ARIA-E cases. These results show that in addition to APOE ε4 allele count, severity of Aβ neuropathology and comorbid cerebrovascular pathology may be relevant for clinicians prescribing anti-Aβ monoclonal antibodies for early AD and developing individualized safety monitoring plans. Evaluation of these risk factors in other anti-Aβ monoclonal antibodies is recommended. ClinicalTrials.gov Identifiers: NCT03444870, NCT03443973, NCT04374253.

Course of brain damage following malignant hypertension.

Malignant hypertension (MHT) crisis triggers widespread microvascular damage, particularly in the brain. Despite recent MRI evidence highlighting acute cerebral injuries during MHT crises, follow-up data remain scarce. This study seeks to fill this gap by exploring how brain MRI markers evolve following acute MHT crisis management. We conducted a retrospective analysis of brain MRI data from MHT patients admitted to Bordeaux University Hospital between 2008 and 2022. Eligible patients had at least one follow-up MRI. Analysis blinded to clinical data was performed to identify markers of posterior reversible encephalopathy syndrome (PRES), acute stroke, cerebral hemorrhage, and microangiopathy. Out of 149 patients, 47 had follow-up MRIs. Most were male (72.3%) with a mean age of 48.2 ± 10.8 years. The median interval between initial and follow-up MRI was 228 days. Follow-up MRIs revealed new strokes in 10.6% of patients, cerebral hemorrhages in 4.3%, and no cases of PRES. Additionally, more patients exhibited chronic lacunar infarcts and/or microbleeds, with overall Fazekas scores remaining stable in 66.0%, improving in 31.9%, and worsening in 2.1%. Subgroup analyses based on blood pressure control or follow-up duration showed no significant differences in MRI markers. This study sheds light on the risk of new cerebrovascular events and the dynamic changes in brain MRI markers following acute MHT crisis management. Understanding these changes could lead to improved diagnosis, personalized treatment strategies, and proactive patient care for individuals with MHT.

A severity comparison of leukoaraiosis in ischemic and hemorrhagic stroke: a retrospective study.

Leukoaraiosis (LA) is a common neuroradiological finding in patients suffering from stroke. Cerebral small-vessel disease (SVD) is one of the primary causes of both ischemic stroke and hemorrhagic stroke (intracerebral hemorrhage, ICH) and the development of LA. Significant evidence that LA predicts the risk of functional dependency and mortality exists. However, studies examining the difference in LA severity between ischemic stroke and hemorrhagic stroke are lacking. We therefore aimed to compare the severity and abundance of LA in the two stroke subgroups. All patients admitted to the Department of Neurology, Haukeland University Hospital, with an ischemic stroke and intracerebral hemorrhagic (ICH) stroke diagnosed between 2006 and 2020 were included in the study. We collected patient data on risk factors and clinical and radiological findings and outcomes from our local stroke registry. The presence and severity of LA were assessed using the Fazekas score based on CT imaging. We evaluated the outcome using the modified Rankin Score (mRS) 7 days post-stroke. A total of 5,084 patients were included in our analyses: 4437 (87%) with ischemic stroke and 647 (13%) with ICH. LA was present in 2476 (45%) patients. In our ordinal logistic regression model, adjusting for age, sex, known hypertension, known diabetes mellitus, and smoking, LA was more severe and more abundant in ICH patients compared to ischemic stroke patients (Fazekas score: 1, OR: 1.54; Fazekas score: 2, OR: 1.88; and Fazekas score: 3, OR 2.13; p < 0.001). Increasing severity of LA was associated with worse functional outcomes in both groups (ischemic stroke, OR: 1.49; p < 0.001 and ICH, OR: 1.36; p < 0.025). In this study, LA was more severe and abundant in patients with ICH.

Cerebral damage after malignant hypertensive crisis: cerebral MRI follow-up data

Abstract Background Malignant hypertension (MHT) crisis is characterized by acute and diffuse microvascular damages, and the brain is a primary target organ. While a recent MRI study has revealed extensive and frequent cerebral injuries during the acute phase of MHT crisis (1), there is a scarcity of follow-up data. Purpose This study aims to investigate the evolution of MRI markers of cerebral injury following the management of the acute phase of MHT. Methods In this retrospective analysis, we examined brain MRI data from patients admitted for acute MHT between 2008 and 2022 at our center. Eligible patients had at least one follow-up brain MRI available. A skilled operator conducted a comprehensive analysis of each brain MRI, searching for posterior reversible encephalopathy syndrome (PRES), acute stroke or cerebral hemorrhage and microangiopathy markers, blinded for clinical and demographical data. Results Among 149 patients enrolled, 104 had a brain MRI at inclusion, 47 individuals had at least one follow-up brain MRI and were included in the analysis. 72,3% were male, mean age was 48,2 ± 10.8 years and 45,7% presented blood pressure control at the time of the follow-up brain MRI. Median interval between initial and follow-up brain MRI was 228 (84 – 726) days. Five (10,6%) new recent strokes, 2 (4,3 %) cerebral hemorrhage and 0 PRES were recorded during follow-up. On the follow-up brain MRI, more patients presented chronic lacunar infarct and/or microbleeds, in higher numbers. On the contrary, overall Fazekas score was stable in 31 patients (66,0%), improved in 15 patients (31,9 %) and worsened in 1 patients (2,1%). Comparison of subgroups dichotomized according to blood pressure control or follow up duration showed no difference in brain MRI markers. Conclusion This study offers valuable insights into the risk of new cerebrovascular events and the evolution of brain MRI markers after managing the acute phase of MHT. Our findings emphasize the dynamic nature of cerebral microvascular burden and the potential for regression of white matter hyperintensities. A better understanding of these phenomena might contribute to improved diagnosis, tailored treatment, and proactive patient care in the context of MHT.

Non-classical monocyte levels correlate negatively with HIV-associated cerebral small vessel disease and cognitive performance.

Despite antiretroviral treatment (cART), aging people living with HIV (PWH) are more susceptible to neurocognitive impairment (NCI) probably due to synergistic/additive contribution of traditional cerebrovascular risk factors. Specifically, transmigration of inflammatory CD16+ monocytes through the altered blood brain barrier (BBB) may exacerbate cerebral small vessel disease (CSVD), a known cause of vascular cognitive impairment. PWH on cART (n=108) and age, sex, and Reynold's cardiovascular risk score-matched uninfected individuals (PWoH, n=111) were enrolled. This is a longitudinal observational study but only cross-sectional data from entry visit are reported. Neuropsychological testing and brain magnetic resonance imaging (MRI) were performed. CSVD was diagnosed by Fazekas score ≥1. Flow cytometric analyses of fresh whole blood were conducted to evaluate circulating levels of monocyte subsets (classical, intermediate, and non-classical) and markers of monocyte activation (CCR2, CD40, PSGL-1, TNFR2 and tissue factor). ELISAs were used to measure sCD14, ICAM, and Osteoprotegerin. Two-way analysis of variance (ANOVA), and linear regression models were performed to study the effects of HIV status, CSVD status, and their interaction to outcome variables such as cognitive score. Two-sample t-tests and correlation analyses were performed between and within PWoH with CSVD and PWH with CSVD participants. PWH with CSVD (n=81) had significantly lower total cognitive scores, higher levels of NCMs and soluble CD14 and intracellular adhesion molecule 1 (ICAM-1) as compared to PWoH with CSVD group (n=68). sCD14 and ICAM1 were positively correlated with each other indicating that monocyte and endothelial activation are associated with each other. Cognition was negatively correlated with NCMs, especially in the PWH with CSVD group. Among other blood biomarkers measured, osteoprotegerin levels showed mild negative correlation with cognitive performance in individuals with CSVD irrespective of HIV status. Elevated levels of NCMs may contribute to neuroinflammation, CSVD and subsequent cognitive impairment. This finding is of particular relevance in aging PWH as both HIV and aging are associated with increased levels of NCMs. NCMs may serve as a potential biomarker to address these comorbidities. Further longitudinal studies are needed to evaluate whether changes in NCM levels are associated with changes in CSVD burden and cognitive impairment.

Cerebral small vessel disease and its relationship with all-cause mortality risk: Results from the Amsterdam Ageing cohort

IntroductionCerebral Small-Vessel Disease (CSVD) is a complex condition affecting the brain's vascular network, linked to cognitive and physical decline, cerebrovascular disease, and death. This study assesses the relationship between CSVD (composite and individual features) and all-cause mortality in a large cohort of geriatric outpatients. MethodsData from 1305 geriatric outpatients (mean age 78 ± 7; 51 % female) in the Amsterdam Ageing cohort were analysed. CSVD presence was based on brain imaging (MRI or CT), defined by a Fazekas score ≥ 2, presence of ≥1 lacunes, or (in MRI) ≥ 3 microbleeds. Mortality data (February 2016 - January 2024) was sourced from the Dutch Municipality Register. The relationship between CSVD and all-cause mortality was evaluated using a Cox proportional-hazards model, adjusting for key confounders. ResultsAt baseline, 835 (64 %) of the 1305 patients had CSVD. During a median follow-up of 3.1 years (IQR 1.6–4.6 years), all-cause mortality was 40 % (333 patients) in the CSVD group and 26 % (121 patients) in the non-CSVD group, corresponding with incidence rates of 137 and 78 per 1000 patient-years, respectively. The age- and sex-adjusted hazard ratio for mortality in the CSVD group was 1.6 (95 % CI: 1.3–2.0). This association remained significant after adjusting for cardiovascular disease and its risk factors, physical function (gait speed), and cognitive function (MMSE). ConclusionRadiographic CSVD presence is prevalent and its integration into daily care is important as it is independently linked to increased all-cause mortality in geriatric outpatients.

Quantitative Analysis of White Matter Hyperintensities as a Predictor of 1-Year Risk for Ischemic Stroke Recurrence.

This study evaluates the role of quantitative characteristics of white matter hyperintensities (WMHs) in predicting the 1-year recurrence risk of ischemic stroke. We conducted a retrospective analysis of 1061 patients with ischemic stroke from January 2018 to April 2021. WMHs were automatically segmented using a cluster-based method to quantify their volume and number of clusters (NoC). Additionally, two radiologists independently rated periventricular and deep WMHs using the Fazekas scale. The cohort was divided into a training set (70%) and a testing set (30%). We employed Cox proportional hazards models to develop predictors based on quantitative WMH characteristics, Fazekas scores, and clinical factors, and compared their performance using the concordance index (C-index). A total of 180 quantitative variables related to WMHs were extracted. A higher NoC in deep white matter and brainstem, advanced age (>90years old), specific stroke subtypes, and absence of discharge antiplatelets showed stronger associations with the risk of ischemic stroke recurrence within 1year. The nomogram incorporating quantitative WMHs data showed superior discrimination compared to those based on the Fazekas scale or clinical factors alone, with C-index values of 0.709 versus 0.647 and 0.648, respectively, in the testing set. Notably, a combined model including both WMHs and clinical factors achieved the highest predictive accuracy, with a C-index of 0.735 in the testing set. Quantitative assessment of WMHs provides a valuable neuro-imaging tool for enhancing the prediction of ischemic stroke recurrence risk.

Outcome of intravenous thrombolysis in acute ischemic stroke patients with small vessel disease

IntroductionLacunar stroke (LS) subtype accounts for a quarter of ischemic strokes. Intravenous thrombolysis (IVT) is known to improve overall stroke outcomes. Very few studies have focused on the outcome of IVT in lacunar strokes. Aim: To detect the outcome of IVT in LS patients compared to non-thrombolysed LS patients. MethodsFifty patients presenting with LS received the standard protocol of IVT (Group I). They were compared to fifty matched LS patients who presented beyond the time window and were selected as the control group (Group II). Clinical outcome was measured using NIHSS within 24 h, NIHSS at discharge, and MRS after 3 months. Risk factors that could have affected clinical outcomes were compared in the thrombolysis group. ResultsThe short-term clinical outcome of Group I showed statistically significant improvement of NIHSS after 24 hrs compared to Group II (mean NIHSS = 5.52±3.89 and 7.44±1.82 respectively), as well as on discharge (mean NIHSS = 3.88±3.50 and 5.78±2.97) respectively. For long-term outcomes, 94 % of GroupⅠ reached MRS 0, 1, and 2 (n = 47/50) versus 74 % (n = 36/50) in Group II. Longer door-to-needle time, severe WMCs (Fazekas score), and pneumonia were shown to be significant predictor factors for the worst outcome. ConclusionIVT has improved short- and long-term outcomes in LS patients. Longer door-to-needle time, severe WMCs, and pneumonia were shown to be significant predictor factors for the worst outcome.

Cerebrovascular Burden and Its Association with Ménière’s Disease: A Case-Control Study

Background: Ménière’s disease (MD) lacks a universally accepted pathogenesis model. Recent research has revisited the vascular hypothesis. This study aims to compare the cerebrovascular burden in patients with MD and age-matched controls, investigating the potential role of cerebrovascular dysfunction in MD. Methods: A total of 145 patients (70 MD, 75 controls) underwent magnetic resonance imaging (MRI) assessment for small-vessel disease (SVD) markers (including Fazekas and EPVS scores), cortical strokes, and baseline comorbidities. Statistical analyses were performed to compare the cerebrovascular burden between the groups, adjusting for potential confounders. Results: The MD group exhibited significantly higher mean SVD scores across various measures compared to controls (p &lt; 0.05). This association persisted even after adjusting for age, sex, and comorbidities (ORs ranging from 1.746 to 2.495, p &lt; 0.05). Neither the presence of cortical strokes nor comorbidities significantly differed between groups. Conclusions: This study is the first to compare cerebrovascular burden between MD patients and controls. The findings suggest that cerebrovascular dysfunction may contribute to MD incidence. Further research is needed to elucidate the relationship between cerebrovascular disease and MD, potentially leading to novel therapeutic avenues.

Baseline and Longitudinal MRI Markers Associated With 16-Year Mortality in Patients With Cerebral Small Vessel Disease.

Information on whether small vessel disease (SVD) reduces life expectancy is limited. Moreover, the excess mortality risk attributed specifically to SVD compared with controls from the general population has not been evaluated. This study aimed to investigate the baseline and progression of MRI markers of SVD associated with mortality in a 16-year follow-up cohort study and to determine the excess long-term mortality risk of patients with SVD. Participants with SVD from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC) study (with MRI assessments in 2006, 2011, 2015, and 2020) were followed until their death or December 1, 2021. Adjusted Cox regression analyses and linear mixed-effect regression models were used to investigate the association between MRI markers of SVD and mortality. The excess mortality risk of SVD was calculated by comparing mortality data of the RUN DMC study with the general population matched by sex, age, and calendar year. 200 of 503 (39.9%) participants died during a follow-up period of 15.9 years. Cause of death was available for 182 (91%) participants. Baseline white matter hyperintensity volume (HR 1.3 per 1-SD increase [95% CI 1.1-1.5], p = 0.010), presence of lacunes (1.5 [95% CI 1.1-2.0], p = 0.008), mean diffusivity (HR 1.1 per 1-SD increase [95% CI 1.1-1.2], p = 0.001), and total brain volume (HR 1.5 per 1-SD decrease [95% CI 1.3-1.9], p < 0.001) were associated with all-cause mortality after adjusting for age, sex, and vascular risk factors. Total brain volume decrease over time was associated with all-cause mortality after adjusting for age, sex, and vascular risk factors (HR 1.3 per 1-SD decrease [95% CI 1.1-1.7], p = 0.035), and gray matter volume decrease remained significant after additionally adjusting for its baseline volume (1.3 per 1-SD decrease [1.1-1.6], p = 0.019). Participants with a Fazekas score of 3, presence of lacunes, or lower microstructural integrity had an excess long-term mortality risk (21.8, 15.7, 10.1 per 1,000 person-years, respectively) compared with the general population. Excess long-term mortality risk only exists in patients with severe SVD (Fazekas score of 3, presence of lacunes, or lower microstructural integrity). This could help in assisting clinicians to predict the clinical outcomes of patients with SVD by severity.

Increased extracellular free water is related to white matter hyperintensity burden.

Extracellular free water (FW) has important roles in the occurrence and development of white matter hyperintensity (WMH). To explore the correlations between FW and WMH burden. A prospective analysis was conducted using magnetic resonance imaging (MRI) data from 126 individuals. WMH burden was determined based on WMH volumes and Fazekas scores from deep and periventricular white matter hyperintensity (DWMH and PWMH, respectively) in fluid-attenuated inversion recovery (FLAIR) images. FW values were taken from diffusion tensor imaging (DTI). Univariate analysis showed that FW values were correlated with WMH burden, including WMH volumes and DWMH and PWMH Fazekas scores (P < 0.05). After multivariate analysis, FW values were correlated with WMH volumes and DWMH and PWMH Fazekas scores when adjusted for age and hypertension (P < 0.05). Using MRI, increasing extracellular FW was related to WMH burden.

Evaluating cochlear implant outcomes in DFNA9 subjects: a comprehensive study on cerebral white matter lesions and vestibular abnormalities.

This study assessed whether the Fazekas score could account for the variability in cochlear implantation (CI) outcomes among individuals with DFNA9 and evaluated signal loss in the semicircular canals (SCCs) on magnetic resonance imaging (MRI) among individuals with DFNA9. This retrospective cross-sectional study included CI recipients with DFNA9. Pre-implantation MRI-scans were reviewed to determine the Fazekas score, localizing and grading cerebral white matter lesions (WML), and identify abnormalities in the SCCs. CI performance was assessed by evaluating phoneme scores one year post-implantation. The function of the SCCs was evaluated using rotatory chair testing with electronystagmography (ENG) and the video Head Impulse Test (vHIT). Forty-five subjects (49 ears) were enrolled. The phoneme scores significantly improved from 35% (IQR 11-50) pre-implantation to 84% (IQR 76-90) one year post-implantation. No correlation was observed between the Fazekas score and the one-year post-implantation phoneme score (rsp=0.003, p = 0.986). Signal loss in at least one SCCs was detected in 97.7% of subjects and 77.8% of ears. There was no correlation between vestibular test results and fluid signal loss in the SCCs on MRI. Most individuals with DFNA9 show improved speech recognition with CI. The observed variability in CI outcomes was not linked to the Fazekas score. Additionally, our study confirms a high prevalence of focal sclerosis in DFNA9. Recognizing the limitations of this study, further research is needed to explore the predictive role of the Fazekas score on CI outcomes and its relationship with vestibular function.

Analysis of predictors of hemorrhagic transformation after reperfusion therapy with recombinant tissue plasminogen activator in patients with acute ischemic stroke: a single-center experience

BackgroundHemorrhagic transformation (HT) is a serious complication of thrombolytic therapy for acute ischemic stroke, limiting its indications and affecting treatment plans and clinical prognosis. Identifying risk factors for HT could help improve the risk–benefit ratio of thrombolytic therapy. We aimed to analyze the predictors of HT after reperfusion therapy with recombinant tissue plasminogen activator (rTPA) in patients with acute ischemic stroke. This study included 115 patients who received rTPA. All patients underwent history taking, clinical examination, neurological examination including Glasgow Coma Scale and National Institutes of Health Stroke Scale scores (NIHSS), radiological investigation, and cardiac investigation. Patients were followed up strictly every 2 h for 1st 24 h then for two weeks clinically using the NIHSS and radiologically using CT or MRI to detect HT.ResultsPatients with HT represented 21.7% of all patients receiving rTPA, while symptomatic intracranial hemorrhage (sICH) represented 6.9%. Patients with HT had significantly higher blood pressure, respiratory rate, atrial fibrillation rate, NIHSS score, INR, prothrombin time, neutrophil-to-lymphocyte ratio (NLR), and lower platelet count, LDL level, higher Fazekas score, lower ASPECT score, and prolonged onset-to-needle time.ConclusionPredicting HT in acute ischemic stroke patients is crucial for optimizing management and potentially improving outcomes. In our study, six predictors were associated with HT: higher respiratory rate, higher atrial fibrillation rate, higher NLR, lower LDL level, higher Fazekas score, lower ASPECT score, and onset-to-needle time greater than 180 min.

Cerebrovascular Reactivity Assessed by Breath-Hold Functional MRI in Patients with Neurological Post-COVID-19 Syndrome-A Pilot Study.

Endothelial dysfunction represents a potential pathomechanism of neurological post-COVID-19 syndrome (PCS). A recent study demonstrated reduced cerebrovascular reactivity (CVR) in patients with PCS. The aim of this pilot study was to prospectively assess CVR in patients with PCS using breath-hold functional MRI (bh-fMRI). Fourteen patients with neurological PCS and leading symptoms of fatigue/memory issues/concentration disorder (PCSfmc), 11 patients with PCS and leading symptoms of myopathy/neuropathy (PCSmn), and 17 healthy controls underwent bh-fMRI. Signal change and time to peak (TTP) were assessed globally and in seven regions of interest and compared between the subgroups using one-way ANCOVA adjusting for age, time since infection, Fazekas score, and sex. No significant differences were observed. In PCS patients, the global CVR exhibited a slight, non-significant tendency to be lower compared to healthy controls (PCSfmc: 0.78 ± 0.11%, PCSmn: 0.84 ± 0.10% and 0.87 ± 0.07%). There was a non-significant trend towards lower global TTP values in the PCS subgroups than in the control group (PCSfmc: 26.41 ± 1.39 s, PCSmn: 26.32 ± 1.36 s versus 29.52 ± 0.93 s). Endothelial dysfunction does not seem to be the sole pathomechanism of neurological symptoms in PCS. Further studies in larger cohorts are required.