Clinical study of cerebral small vessel disease

Ageing and hypertension are the main causes of cerebral small vessel disease (SVD) known until today. Endothelial dysfunction, rupture of blood-brain barrier (BBB) and protein elimination failure angiopathy have become important in its pathophysiology. The main objectives of the study are identify the clinical risk profile and biomarkers of cognitive impairment (A 1-40), endothelial dysfunction (sTWEAK) and extracellular matrix dysfunction (MMPs) associated with initial phases or with the development of SVD. A prospective study was designed including long time hypertensive and diabetic patients with age between 60-75 years. Cognitive and neuroradiological evaluation were done; and ELISA tests were performed to determinate the serum concentration of sTWEAK, AB1-40, TIMP1, MMP-1, MMP-10, MMP-7, MMP-9, MMP-12, MMP-13 and MMP-3. Main results were bad clinical control of hypertension is the main factor associated with progression of SVD; sTWEAK, MMP7, MMP9 and AB 1-40 could be potential biomarkers related with progression of SVD

Influence of Sex on Stroke Prognosis: A Demographic, Clinical, and Molecular Analysis

Identifying the complexities of the effect of sex on stroke risk, etiology, and lesion progression may lead to advances in the treatment and care of ischemic stroke (IS) and non-traumatic intracerebral hemorrhage patients (ICH). We studied the sex-related discrepancies on the clinical course of patients with IS and ICH, and we also evaluated possible molecular mechanisms involved. The study's main variable was the patient's functional outcome at 3-months. Logistic regression models were used in order to study the influence of sex on different inflammatory, endothelial and atrial dysfunction markers. We recruited 5,021 patients; 4,060 IS (54.8% male, 45.2% female) and 961 ICH (57.1% male, 42.9% female). Women were on average 5.7 years older than men (6.4 years in IS, 5.1 years in ICH), and more likely to have previous poor functional status, to suffer atrial fibrillation and to be on anticoagulants. IS patients showed sex-related differences at 3-months regarding poorer outcome (55.6% women, 43.6% men, p < 0.0001), but this relationship was not found in ICH (56.8% vs. 61.9%, p = 0.127). In IS, women had higher levels of NT-proBNP and 3-months worse outcome in both cardioembolic and non-cardioembolic stroke patients. Stroke patients showed sex-related differences in pre-hospital data, clinical variables and molecular markers, but only IS patients presented independent sex-related differences in 3-months poor outcome and mortality. There was a relationship between the molecular marker of atrial dysfunction NT-proBNP and worse functional outcome in women, resulting in a possible indicator of increased dysfunction

Periodontitis is associated with subclinical cerebral and carotid atherosclerosis in hypertensive patients: A cross‑sectional study

Objective: To examine the relationship between periodontitis and subclinical intracranial atherosclerosis. The association of periodontitis with preclinical markers of atherosclerosis in other vascular territories was also explored. Material and methods: This was a cross-sectional study where 97 elderly subjects with a previous history of hypertension received an ultrasonographic evaluation to assess subclinical atherosclerosis in different vascular territories: (1) cerebral [pulsatility (PI) and resistance index (RI) of the middle cerebral artery], (2) carotid [intima-media thickness (IMT)], and (3) peripheral [ankle-brachial index (ABI)]. Additionally, participants underwent a full-mouth periodontal assessment together with blood sample collection to determine levels of inflammatory biomarkers (leukocytes, fibrinogen, and erythrocyte sedimentation rate), lipid fractions (total cholesterol and high- and low-density lipoprotein), and glucose. Results: Sixty-one individuals had periodontitis. Compared to subjects without periodontitis, those with periodontitis showed higher values of PI (1.24 ± 0.29 vs 1.01 ± 0.16), RI (0.70 ± 0.14 vs 0.60 ± 0.06), and IMT (0.94 ± 0.15 vs 0.79 ± 0.15) (all p < 0.001). No statistically significant differences were found neither for ABI or for other clinical and biochemical parameters. An independent association was found between periodontitis and increased intracranial atherosclerosis (ORadjusted = 10.16; 95% CI: 3.14-32.90, p < 0.001) and to a lesser extent with thicker carotid IMT (ORadjusted = 4.10; 95% CI: 1.61-10.48, p = 0.003). Conclusions: Periodontitis is associated with subclinical atherosclerosis in both intracranial and carotid arteries in elderly subjects with hypertension. Clinical relevance: The association of periodontitis with intracranial atherosclerosis implies that periodontitis patients might have greater chances to develop ischemic stroke in the futureOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This study was partially supported by grants from the Xunta de Galicia (TS: IN607A2018/3 and TS: IN607D 2020/09), Spanish Ministry of Science (TS: RTI2018-102165-B-I00 and RTC2019-007373-1), Institute of Health Carlos III (PI22/00938), and RICOR-ICTUS Network (RD21/0006/003). Furthermore, this study was also supported by grants from the Interreg Atlantic Area (TS: EAPA_791/2018_ NeuroATLANTIC project), Interreg V-A España Portugal (POCTEP) (TS: 0624_2IQBIONEURO_6_E), and the European Regional Development Fund. YL is supported by a Sara Borrell fellowship (CD22/00051), and TS (CPII17/00027) and FC (CPII19/00020) are recipients of Miguel Servet contracts, all of them funded by the Institute of Health Carlos IIIS

Random Forest-Based Prediction of Stroke Outcome

[Abstract] We research into the clinical, biochemical and neuroimaging factors associated with the outcome of stroke patients to generate a predictive model using machine learning techniques for prediction of mortality and morbidity 3-months after admission. The dataset consisted of patients with ischemic stroke (IS) and non-traumatic intracerebral hemorrhage (ICH) admitted to Stroke Unit of a European Tertiary Hospital prospectively registered. We identified the main variables for machine learning Random Forest (RF), generating a predictive model that can estimate patient mortality/morbidity according to the following groups: (1) IS + ICH, (2) IS, and (3) ICH. A total of 6022 patients were included: 4922 (mean age 71.9 ± 13.8 years) with IS and 1100 (mean age 73.3 ± 13.1 years) with ICH. NIHSS at 24, 48 h and axillary temperature at admission were the most important variables to consider for evolution of patients at 3-months. IS + ICH group was the most stable for mortality prediction [0.904 ± 0.025 of area under the receiver operating characteristics curve (AUC)]. IS group presented similar results, although variability between experiments was slightly higher (0.909 ± 0.032 of AUC). ICH group was the one in which RF had more problems to make adequate predictions (0.9837 vs. 0.7104 of AUC). There were no major differences between IS and IS + ICH groups according to morbidity prediction (0.738 and 0.755 of AUC) but, after checking normality with a Shapiro Wilk test with the null hypothesis that the data follow a normal distribution, it was rejected with W = 0.93546 (p-value < 2.2e−16). Conditions required for a parametric test do not hold, and we performed a paired Wilcoxon Test assuming the null hypothesis that all the groups have the same performance. The null hypothesis was rejected with a value < 2.2e−16, so there are statistical differences between IS and ICH groups. In conclusion, machine learning algorithms RF can be effectively used in stroke patients for long-term outcome prediction of mortality and morbidity.This study was partially supported by grants from the Spanish Ministry of Science and Innovation (SAF2017-84267-R), Xunta de Galicia (Axencia Galega de Innovación (GAIN): IN607A2018/3), Instituto de Salud Carlos III (ISCIII) (PI17/00540, PI17/01103), Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS PLUS (RD16/0019) and by the European Union FEDER program. T. Sobrino (CPII17/00027), F. Campos (CPII19/00020) are recipients of research contracts from the Miguel Servet Program (Instituto de Salud Carlos III). General Directorate of Culture, Education and University Management of Xunta de Galicia (ED431G/01,252 ED431D 2017/16), “Galician Network for Colorectal Cancer Research" (Ref. ED431D 2017/23), Competitive Reference Groups (ED431C 2018/49), Spanish Ministry of Economy and Competitiveness via funding of the unique installation BIOCAI (UNLC08-1E-002, UNLC13-13–3503), European Regional Development Funds (FEDER).Xunta de Galicia; IN607A2018/3Xunta de Galicia; ED431G/01,252Xunta de Galicia; ED431D 2017/1

Temperature-Induced Changes in Reperfused Stroke: Inflammatory and Thrombolytic Biomarkers

Although hyperthermia is associated with poor outcomes in ischaemic stroke (IS), some studies indicate that high body temperature may benefit reperfusion therapies. We assessed the association of temperature with effective reperfusion (defined as a reduction of ≥8 points in the National Institute of Health Stroke Scale (NIHSS) within the first 24 h) and poor outcome (modified Rankin Scale (mRS) > 2) in 875 retrospectively-included IS patients. We also studied the influence of temperature on thrombolytic (cellular fibronectin (cFn); matrix metalloproteinase 9 (MMP-9)) and inflammatory biomarkers (tumour necrosis factor-alpha (TNF-α), interleukin 6 (IL-6)) and their relationship with effective reperfusion. Our results showed that a higher temperature at 24 but not 6 h after stroke was associated with failed reperfusion (OR: 0.373, p = 0.001), poor outcome (OR: 2.190, p = 0.005) and higher IL-6 levels (OR: 0.958, p 37.5 °C at 24 h, but not at 6 h after stroke, is correlated with reperfusion failure, poor clinical outcome, and infarct size. Mild hyperthermia (36.5–37.5 °C) in the first 6 h window might benefit drug reperfusion therapies by promoting clot lysisThis study was partially supported by grants from the Spanish Ministry of Science and Innovation (SAF2017-84267-R), Xunta de Galicia (Consellería Educación: IN607A2018/3), Instituto de Salud Carlos III (ISCIII) (PI17/00540 and PI17/01103), Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS PLUS (RD16/0019), and by the European Union FEDER program. Furthermore, Tomás. Sobrino (CPII17/00027) and Francisco Campos (CPII19/00020) are recipients of research contracts from the Miguel Servet Program of Instituto de Salud Carlos III. María Pérez-Mato is a Sara Borrell Researcher (CD19/00033)S

Association of periodontitis with cognitive decline and its progression: Contribution of blood‐based biomarkers of Alzheimer's disease to this relationship

Aim To assess whether periodontitis is associated with cognitive decline and its progression as well as with certain blood-based markers of Alzheimer's disease. Materials and Methods Data from a 2-year follow-up prospective cohort study (n = 101) was analysed. Participants with a previous history of hypertension and aged ≥60 years were included in the analysis. All of them received a full-mouth periodontal examination and cognitive function assessments (Addenbrooke's Cognitive Examination (ACE) and Mini-Mental State Examination [MMSE]). Plasma levels of amyloid beta (Aβ)1-40, Aβ1-42, phosphorylated and total Tau (p-Tau and t-Tau) were determined at baseline, 12 and 24 months. Results Periodontitis was associated with poor cognitive performance (MMSE: β = −1.5 [0.6]) and progression of cognitive impairment (hazard ratio [HR] = 1.8; 95% confidence interval: 1.0–3.1). Subjects with periodontitis showed greater baseline levels of p-Tau (1.6 [0.7] vs. 1.2 [0.2] pg/mL, p < .001) and Aβ1-40 (242.1 [77.3] vs. 208.2 [73.8] pg/mL, p = .036) compared with those without periodontitis. Concentrations of the latter protein also increased over time only in the periodontitis group (p = .005). Conclusions Periodontitis is associated with cognitive decline and its progression in elderly patients with a previous history of hypertension. Overexpression of p-Tau and Aβ1-40 may play a role in this associationThis study was partially supported by grants from the Xunta de Galicia (TS & JC: IN607A2018/3, TS: IN607D 2020/09 and IN607A2022/07), Institute of Health Carlos III (TS: PI22/00938 and CB22/05/00067) and Spanish Ministry of Science (TS: RTI2018-102165-B-I00 and RTC2019-007373-1). Furthermore, this study was also supported by grants from the INTERREG Atlantic Area (TS: EAPA_791/2018_NEUROATLANTIC project), INTER-REG V A España Portugal (POCTEP) (TS: 0624_2IQBIONEURO_6_E) and the European Regional Development Fund. Moreover, several members of the research team are supported by the Institute of Health Carlos III: MAN holds an iPFIS contract (IFI18/00008), DR-S and YL are recipients of a Sara Borrell fellowship (CD21/00166 and CD22/00051, respectively) and TS held a Miguel Servet contract (CPII17/00027). Finally, AC is supported by a predoc contract of Xunta de Galicia (IN606A-2021/015). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscriptS