Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. Early identification of dyslipidemia associated with cerebral atherosclerosis is of great importance for reducing the risk of IS. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a novel lipid biomarker to assess atherosclerosis. The aim of this study is to investigate the association between NHHR and cerebral atherosclerotic stenosis using DSA imaging data, including intracranial/extracranial stenosis, anterior/posterior circulation stenosis, severe stenosis, and symptomatic stenosis. Patients who underwent DSA examination from July 2022 to December 2024 were included. Participants were divided into four groups based on NHHR levels. Univariable and multivariable logistic regression were applied to assess the association between NHHR and cerebral atherosclerotic stenosis, including intracranial and extracranial stenosis, anterior and posterior circulation stenosis, severe stenosis, and symptomatic stenosis. Restricted cubic splines (RCS) were applied to analyze and visualize the association between NHHR and cerebral atherosclerotic stenosis. A total of 853 patients were included in the final analysis. After adjusting for covariables, compared to patients in the lower NHHR groups, those in the higher NHHR groups had a significantly higher occurrence rate of extracranial stenosis, posterior circulation stenosis, severe stenosis, and symptomatic stenosis. Multivariable-adjusted RCS showed a nonlinear association between NHHR and posterior circulation stenosis, and a linear positive association between NHHR and symptomatic stenosis. NHHR may serve as a lipid management indicator for patients with extracranial stenosis, posterior circulation stenosis, severe stenosis, or symptomatic stenosis. NHHR could be an independent risk factor for symptomatic stenosis, which can aid in risk stratification and treatment decision-making for cerebral atherosclerotic stenosis patients.

Background and purpose: Previous studies have shown that human herpes simplex virus (HSV) infection may be associated with the onset of headache or migraine. We aimed to investigate the association between HSV infection and severe headache or migraine.Materials and methods: The cross-sectional data on 5,730 participants aged 20–49 years were obtained from the 1999–2004 National Health and Nutrition Examination Survey (NHANES). We used weighted logistic regression analysis to assess the association between HSV infection (HSV-1 gG-1 and HSV-2 gG-2) and severe headache or migraine, and performed subgroup analyses.Results: Our study found that women, higher education, higher body mass index, better family conditions, smoking and alcohol consumption were all associated with severe headaches or migraines. After adjusting for confounding factors such as sex, age, race, and education, HSV-2 (+) was still significantly associated with severe headache or migraine (OR = 1.22, 95%CI:1.03–1.46, p = 0.0443). In subgroup analyses, we found that participants with HSV-1 (−) and HSV-2 (+) were also significantly associated with severe headache or migraine (OR = 1.41, 95%CI:1.04–1.91, p = 0.0281).Conclusion: HSV-2 gG-2(+) was significantly associated with severe headache or migraine.

Inflammation may be related to structural changes in the cerebral cortex. We aimed to explore whether cytokines mediate the link between these changes and primary headache. The summary statistics of genome-wide association study (GWAS) related to migraine and its subtypes, cluster headache were derived from the FinnGen Release 10 database, and tension-type headache data was from the GWAS Catalog. Ninety-one cytokines were obtained from genome-wide pQTL mapping data. GWAS data on cortical surface area (SA) and thickness (TH) came from the ENIGMA Consortium. The methods of Mendelian randomization (MR) analysis included the inverse-variance-weighted (IVW), MR-Egger, and weighted median. Migraine reduces the SA of paracentral[β = −1.3645, OR = 0.2555, 95%CI (0.0660, 0.9898)] by fibroblast growth factor-23(FGF-23), with an intermediate ratio (IR) of 38.13%. Migraine may reduce the TH of superior parietal[β = −0.0029, OR = 0.9971, 95%CI (0.9943, 0.9999)] by interleukin (IL)-15RA, with an absolute IR of 11.11%. Migraine without aura may reduce the TH of rostral anterior cingulate[β = −0.0005, OR = 0.9995, 95%CI (0.9991, 0.9999)] by IL-18R1, with an IR of 11.63%. FGF23 and IL-15RA are associated with reduced SA or TH in migraine, while IL-18R1 is associated with increased TH in migraine without aura.

Background: Recent studies have shown that alkaline phosphatase to albumin ratio (APAR) is a prognostic biomarker for coronary heart disease and cancer. However, the effect of APAR on the prognosis of ischemic stroke (IS) remains unclear. We aimed to assess the association of APAR with all-cause mortality in critically ill patients with IS.Methods: Critically ill patients with IS were identified from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) Version 3.0 database, and classified into quartiles based on APAR index levels. Clinical outcomes included all-cause mortality at 28-days, 90-days and 365-days after admission. Cox proportional hazards regression analysis and restricted cubic spline method were used to clarify the relationship between APAR index and clinical outcomes in critically ill patients with IS.Results: A total of 1,690 critically ill patients with IS were selected from the MIMIC-IV database. Multivariate Cox proportional hazard analysis showed that increased APAR index was significantly associated with all-cause mortality. After adjusting for potential confounding factors, patients with higher APAR (Q4: 1.524–2.794) had significantly increased all-cause mortality at 28-days, 90-days, and 365-days after admission (HR 2.05, 95%CI 1.47–2.86, p = 0; HR 2.09, 95%CI 1.53–2.85, p = 0; HR 2.11, 95%CI 1.55–2.87, p = 0). APAR had a linear relationship with 28-days and 365-days mortality (P for non-linearity: 0.098 and 0.051), but a nonlinear relationship with 90-days mortality (P for non-linearity: 0.042). Subgroup analyses further revealed that higher APAR was also associated with increased long-term mortality in IS patients without hypertension, DM, cardiovascular disease, liver disease or CKD. In addition, we did not observe any interaction between subgroup variables and APAR.Conclusion: A higher APAR index was significantly associated with increased all-cause mortality at 28-days, 90-days and 365-days after admission for critically ill patients with IS. The APAR index may help identify patients with IS at high risk of all-cause death.

Background: A considerable number of patients with acute ischaemic stroke (AIS) are ineligible for standard reperfusion therapy due to time window constraints and contraindications. Human urinary kallidinogenase (HUK), a tissue kallikrein, has been demonstrated to promote vasodilation and improve cerebral blood flow (CBF) in ischaemic regions. Although clinical evidence suggests its favourable efficacy in such patients with AIS, the specific effects of HUK on early cerebral perfusion and its correlation with functional outcomes remain incompletely elucidated. Aim: TK-SPEED aims to investigate the effects of HUK on early cerebral perfusion improvement and functional outcomes in patients with AIS, providing robust evidence for HUK. Methods and design: TK-SPEED is a multicentre, prospective, randomised, open-label, blinded-endpoint controlled trial. Approximately 540 participants with acute anterior circulation ischaemic stroke will be recruited from about 20 participating sites across China. Eligible patients will be randomly assigned in a 1:1 ratio to either the intervention group (HUK plus standard therapy) or the control group (standard therapy). Study outcomes: The primary endpoint is the proportion of patients with a modified Rankin Scale (mRS) of 0–2 at day 90. The secondary outcomes include changes in the Tmax (time-to-maximum)>6 s volume and regional CBF in the Tmax>6 s area on CT perfusion from baseline to day 5 after treatment, the ordinal distribution of mRS, the proportion of patients with mRS of 0–1 at day 90 and changes in the National Institutes of Health Stroke Scale score from baseline to days 5 and 10 after treatment. Discussion: This trial will provide crucial evidence elucidating the impact of HUK on early cerebral perfusion and its correlation with the 90-day neurological outcomes in patients with AIS, offering guidance for optimising AIS treatment strategies and improving patient prognosis. Trial registration number: NCT06132880 .

Background: Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative conditions. Chronic peripheral inflammation has been implicated in the pathophysiology of AD. Given their accessibility and cost-effectiveness, peripheral inflammatory biomarkers hold promise as potential indicators for AD. However, their associations with cognitive function and brain structural abnormalities may vary across patients and age groups. Methods: Patients diagnosed with AD or AD-related mild cognitive impairment (AD-MCI) were included. Peripheral inflammatory biomarkers, including white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), and monocyte count (MONO), were obtained from complete blood count (CBC). Composite inflammatory biomarkers were calculated from the aforementioned parameters and included the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-platelet ratio (NPR), neutrophil-monocyte-to-lymphocyte ratio (NMLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI). We examined the associations of peripheral blood inflammatory biomarkers and calculated composite inflammatory biomarkers with cognitive function, global cortical atrophy, and hippocampal atrophy. Interaction and stratified analyses were employed to investigate the modifying effects of age and sex on these associations. Results: The study included a total of 395 patients. Within the overall sample, almost all inflammatory biomarkers did not exhibit significant associations with cognitive function, global cortical atrophy, or hippocampal atrophy. Interaction analyses revealed significant interactions between age and several inflammatory biomarkers, while no significant interactions were detected concerning sex. Stratified analyses indicated that among patients younger than 75 years, several composite inflammatory biomarkers were significantly associated with cognitive function, global cortical atrophy, and hippocampal atrophy, whereas no significant associations were observed in patients aged 75 years or older. Conclusion: In patients with AD and AD-MCI, the associations between peripheral inflammatory biomarkers and both cognitive impairment and structural brain abnormalities were found to be age-dependent, with stronger associations observed in patients younger than 75 years. Several composite inflammatory biomarkers showed more consistent associations and may help characterize heterogeneity within this clinical population, although their prognostic and diagnostic value requires further validation.