Intracerebral haemorrhage pathophysiology: time is brain

Intracerebral haemorrhage is associated with high mortality and morbidity. Cerebral small vessel disease, either due to hypertensive small vessel disease or to amyloid angiopathy, is the common substrate for primary spontaneous intracerebral haemorrhage.The current understanding of brain injury induced by intracerebral haemorrhage is based on both clinical and experimental studies. The initial injury immediately after its onset is from the direct mechanical force of the expanding hematoma, resulting in cytotoxic edema and cellular necrosis. After this, the degrading hematoma releases its breakdown products, which lead to the activation of oxygen free radicals, matrix metalloproteinases, complement proteins and inflammatory markers, thus determining an increase of the BBB permeability, the recruitment of inflammatory cells, apoptosis, and ultimately the exacerbation of cerebral edema and neuronal death.Evidence suggests that early and aggressive medical management and specialist care can improve the overall outcome in patients with intracerebral haemorrhage. The growing insight into the molecular pathophysiological mechanisms may contribute to the development of neuroprotective strategies

Prediction of Impaired Performance in Trail Making Test in MCI Patients With Small Vessel Disease Using DTI Data

Mild cognitive impairment (MCI) is a common condition in patients with diffuse hyperintensities of cerebral white matter (WM) in T2-weighted magnetic resonance images and cerebral small vessel disease (SVD). In MCI due to SVD, the most prominent feature of cognitive impairment lies in degradation of executive functions, i.e., of processes that supervise the organization and execution of complex behavior. The trail making test is a widely employed test sensitive to cognitive processing speed and executive functioning. MCI due to SVD has been hypothesized to be the effect of WM damage, and diffusion tensor imaging (DTI) is a well-established technique for in vivo characterization of WM. We propose a machine learning scheme tailored to 1) predicting the impairment in executive functions in patients with MCI and SVD, and 2) examining the brain substrates of this impairment. We employed data from 40 MCI patients with SVD and created feature vectors by averaging mean diffusivity (MD) and fractional anisotropy maps within 50 WM regions of interest. We trained support vector machines (SVMs) with polynomial as well as radial basis function kernels using different DTI-derived features while simultaneously optimizing parameters in leave-one-out nested cross validation. The best performance was obtained using MD features only and linear kernel SVMs, which were able to distinguish an impaired performance with high sensitivity (72.7%-89.5%), specificity (71.4%-83.3%), and accuracy (77.5%-80.0%). While brain substrates of executive functions are still debated, feature ranking confirm that MD in several WM regions, not limited to the frontal lobes, are truly predictive of executive functions

Relationship between progression of brain white matter changes and late-life depression: 3-year results from the LADIS study

Background: Brain white matter changes (WMC) and depressive symptoms are linked, but the directionality of this association remains unclear. Aims: To investigate the relationship between baseline and incident depression and progression of white matter changes. Method: In a longitudinal multicentre pan-European study (Leukoaraiosis and Disability in the elderly, LADIS), participants aged over 64 underwent baseline magnetic resonance imaging (MRI) and clinical assessments. Repeat scans were obtained at 3 years. Depressive outcomes were assessed in terms of depressive episodes and the Geriatric Depression Scale (GDS). Progression of WMC was measured using the modified Rotterdam Progression scale. Results: Progression of WMC was significantly associated with incident depression during year 3 of the study (P = 0.002) and remained significant after controlling for transition to disability, baseline WMC and baseline history of depression. There was no significant association between progression of WMC and GDS score, and no significant relationship between progression of WMC and history of depression at baseline. Conclusions: Our results support the vascular depression hypothesis and implicate WMC as causal in the pathogenesis of late-life depression.Full Tex

Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort

Objective To assess the impairment in daily living activities in older people with age related changes in white matter according to the severity of these changes

Risk and Determinants of Dementia in Patients with Mild Cognitive Impairment and Brain Subcortical Vascular Changes: A Study of Clinical, Neuroimaging, and Biological Markers—The VMCI-Tuscany Study: Rationale, Design, and Methodology

Dementia is one of the most disabling conditions. Alzheimer's disease and vascular dementia (VaD) are the most frequent causes. Subcortical VaD is consequent to deep-brain small vessel disease (SVD) and is the most frequent form of VaD. Its pathological hallmarks are ischemic white matter changes and lacunar infarcts. Degenerative and vascular changes often coexist, but mechanisms of interaction are incompletely understood. The term mild cognitive impairment defines a transitional state between normal ageing and dementia. Pre-dementia stages of VaD are also acknowledged (vascular mild cognitive impairment, VMCI). Progression relates mostly to the subcortical VaD type, but determinants of such transition are unknown. Variability of phenotypic expression is not fully explained by severity grade of lesions, as depicted by conventional MRI that is not sensitive to microstructural and metabolic alterations. Advanced neuroimaging techniques seem able to achieve this. Beside hypoperfusion, blood-brain-barrier dysfunction has been also demonstrated in subcortical VaD. The aim of the Vascular Mild Cognitive Impairment Tuscany Study is to expand knowledge about determinants of transition from mild cognitive impairment to dementia in patients with cerebral SVD. This paper summarizes the main aims and methodological aspects of this multicenter, ongoing, observational study enrolling patients affected by VMCI with SVD

Do the current guidelines for heart failure diagnosis and treatment fit with clinical complexity?

Heart failure (HF) is a clinical syndrome defined by specific symptoms and signs due to structural and/or functional heart abnormalities, which lead to inadequate cardiac output and/or increased intraventricular filling pressure. Importantly, HF becomes progressively a multisystemic disease. However, in August 2021, the European Society of Cardiology published the new Guidelines for the diagnosis and treatment of acute and chronic HF, according to which the left ventricular ejection fraction (LVEF) continues to represent the pivotal parameter for HF patients' evaluation, risk stratification and therapeutic management despite its limitations are well known. Indeed, HF has a complex pathophysiology because it first involves the heart, progressively becoming a multisystemic disease, leading to multiorgan failure and death. In these terms, HF is comparable to cancer. As for cancer, surviving, morbidity and hospitalisation are related not only to the primary neoplastic mass but mainly to the metastatic involvement. In HF, multiorgan involvement has a great impact on prognosis, and multiorgan protective therapies are equally important as conventional cardioprotective therapies. In the light of these considerations, a revision of the HF concept is needed, starting from its definition up to its therapy, to overcome the old and simplistic HF perspective