Alzheimer’s disease (AD), the most common form of neurodegenerative dementia in adults worldwide, is a multifactorial and heterogeneous disorder characterized by the interaction of genetic and epigenetic factors and the dysregulation of numerous intracellular signaling and cellular/molecular pathways. The introduction of the systems biology framework is revolutionizing the study of complex diseases by allowing the identification and integration of cellular/molecular pathways and networks of interaction. Here, we reviewed the relationship between physical activity and the next pathophysiological processes involved in the risk of developing AD, based on some crucial molecular pathways and biological process dysregulated in AD: (1) Immune system and inflammation; (2) Endothelial function and cerebrovascular insufficiency; (3) Apoptosis and cell death; (4) Intercellular communication; (5) Metabolism, oxidative stress and neurotoxicity; (6) DNA damage and repair; (7) Cytoskeleton and membrane proteins; (8) Synaptic plasticity. Moreover, we highlighted the increasingly relevant role played by advanced neuroimaging technologies, including structural/functional magnetic resonance imaging, diffusion tensor imaging, and arterial spin labelling, in exploring the link between AD and physical exercise. Regular physical exercise seems to have a protective effect against AD by inhibiting different pathophysiological molecular pathways implicated in AD.

Posterior reversible encephalopathy syndrome (PRES) is a serious adverse event associated with calcineurin inhibitors used for graft-versus-host disease (GVHD) prophylaxis. We compared the incidence of PRES in children with thalassemia (n = 222, 1.4 to 17.8 years old) versus sickle cell disease (SCD; n = 59, 2 to 17 years old) who underwent hematopoietic cell transplantation from HLA-matched siblings or alternative donors and analyzed the risk factors for PRES. Overall, 31 children developed calcineurin inhibitor-related PRES (11%), including 30 patients with seizures and 1 patient without seizures. PRES incidence was significantly higher in SCD patients (22%; 95% confidence interval [CI], 10% to 32%) than in thalassemia patients (8%; 95% CI, 5% to 12%;P = .002). In multivariate analysis, factors associated with PRES were hypertension (hazard ratio [HR], 5.87; 95% CI, 2.57 to 13.43; P = .0001), SCD (HR, 2.49; 95% CI, 1.25 to 4.99; P = .009), and acute GVHD (HR 2.27; 95% CI, 1.06 to 4.85; P= .031). In the entire cohort overall survival (OS) was significantly higher in patients without versus with PRES (90% versus 77%; P = .02). In a subgroup analysis that including matched sibling transplants, OS and disease-free survival (DFS) were similar in thalassemia patients without PRES (92% and 88%, respectively) and with PRES (82% and 73%, respectively), whereas SCD patients with PRES had significantly lower OS (67%) and DFS (67%) than patients without PRES (94% and 94%, respectively; P = .008). Thus, SCD patients had a significantly higher incidence of PRES than thalassemia patients, and hypertension and GVHD were the 2 main risk factors for PRES in patients with hemoglobinopathies. Although PRES did not significantly influence survival in patients with thalassemia, patients with SCD had significantly lower survival after PRES.

Objective To investigate the efficacy of tenecteplase (TNK), a genetically modified variant of alteplase with greater fibrin specificity and longer half-life than alteplase, prior to endovascular thrombectomy (EVT) in patients with basilar artery occlusion (BAO). Methods To determine whether TNK is associated with better reperfusion rates than alteplase prior to EVT in BAO, clinical and procedural data of consecutive patients with BAO from the Basilar Artery Treatment and Management (BATMAN) registry and the Tenecteplase vs Alteplase before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trial were retrospectively analyzed. Reperfusion >50% or absence of retrievable thrombus at the time of the initial angiogram was evaluated. Results We included 110 patients with BAO treated with IV thrombolysis prior to EVT (mean age 69 [SD 14] years; median NIH Stroke Scale score 16 [interquartile range (IQR) 7–32]). Nineteen patients were thrombolysed with TNK (0.25 mg/kg or 0.40 mg/kg) and 91 with alteplase (0.9 mg/kg). Reperfusion >50% occurred in 26% (n = 5/19) of patients thrombolysed with TNK vs 7% (n = 6/91) thrombolysed with alteplase (risk ratio 4.0, 95% confidence interval 1.3–12; p = 0.02), despite shorter thrombolysis to arterial puncture time in the TNK-treated patients (48 [IQR 40–71] minutes) vs alteplase-treated patients (110 [IQR 51–185] minutes; p = 0.004). No difference in symptomatic intracranial hemorrhage was observed (0/19 [0%] TNK, 1/91 [1%] alteplase; p = 0.9). Conclusions TNK may be associated with an increased rate of reperfusion in comparison with alteplase before EVT in BAO. Randomized controlled trials to compare TNK with alteplase in patients with BAO are warranted. Clinicaltrials.gov Identifiers NCT02388061 and NCT03340493. Classification of Evidence This study provides Class III evidence that TNK leads to higher reperfusion rates in comparison with alteplase prior to EVT in patients with BAO.

Functional magnetic resonance imaging may provide several quantitative indices strictly related to distinctive tissue signatures with radiobiological relevance, such as tissue cellular density and vascular perfusion. The role of Intravoxel Incoherent Motion Diffusion Weighted Imaging (IVIM-DWI) and Dynamic Contrast-Enhanced (DCE) MRI in detecting/predicting radiation-induced volumetric changes of parotids both during and shortly after (chemo)radiotherapy of oropharyngeal squamous cell carcinoma (SCC) was explored. Patients with locally advanced oropharyngeal SCC were accrued within a prospective study offering both IVIM-DWI and DCE-MRI at baseline; IVIM-DWI was repeated at the 10th fraction of treatment. Apparent diffusion coefficient (ADC), tissue diffusion coefficient Dt, perfusion fraction f and perfusion-related diffusion coefficient D* were estimated both at baseline and during RT. Semi-quantitative and quantitative parameters, including the transfer constant Ktrans, were calculated from DCE-MRI. Parotids were contoured on T2-weighted images at baseline, 10th fraction and 8th weeks after treatment end and the percent change of parotid volume between baseline/10th fr (∆Vol10fr) and baseline/8th wk. (∆Volpost) computed. Correlations among volumetric changes and patient-, treatment- and imaging-related features were investigated at univariate analysis (Spearman’s Rho). Eighty parotids (40 patients) were analyzed. Percent changes were 18.2 ± 10.7% and 31.3 ± 15.8% for ∆Vol10fr and ∆Volpost, respectively. Among baseline characteristics, ∆Vol10fr was correlated to body mass index, patient weight as well as the initial parotid volume. A weak correlation was present between parotid shrinkage after the first 2 weeks of treatment and dosimetric variables, while no association was found after radiotherapy. Percent changes of both ADC and Dt at the 10th fraction were also correlated to ∆Vol10fr. Significant relationships were found between ∆Volpost and baseline DCE-MRI parameters. Both IVIM-DWI and DCE-MRI can help to detect/predict early (during treatment) and shortly after treatment completion the parotid shrinkage. They may contribute to clarify the correlations between volumetric changes of parotid glands and patient−/treatment-related variables by assessing individual microcapillary perfusion and tissue diffusivity.

Background: CT perfusion may improve diagnostic accuracy in posterior circulation stroke. The posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) on Computed Tomography Angiography source images (CTA-SI) predicts functional outcome in patients with basilar artery occlusion. Aims: We assessed the prognostic value of pc-ASPECTS on CT perfusion in patients with vertebral and basilar artery occlusion (VBAO) in comparison with CTA-SI. Methods: Whole-brain CT perfusion from consecutive stroke patients with VBAO at four stroke centers was retrospectively analyzed. pc-ASPECTS – a 10-point score assessing hypoattenuation on CTA-SI – was calculated from CT perfusion parameters as focally reduced cerebral blood flow or cerebral blood volume, focally increased time to peak of the deconvolved tissue residue function (Tmax) or mean transit time. Two investigators independently reviewed the images. Reliability was assessed with intraclass correlation coefficient. Good outcome was defined as modified Rankin scale ≤3 at three months. Results: We included 60 patients with VBAO. After assessment of four CT perfusion maps simultaneously, area-under-ROC curve (AROC) was 0.83 (95%CI 0.72–0.93) for cerebral blood volume, 0.76 (95%CI 0.64–0.89) for cerebral blood flow, 0.77 (95%CI 0.64–0.89) for Tmax, 0.70 (95%CI 0.56–0.84) for mean transit time versus area-under-ROC curve 0.64 (95%CI 0.50–0.79) for CTA-SI. Cerebral blood volume had greater accuracy compared with CTA-SI for poor outcome (p = 0.04). In logistic regression analysis, cerebral blood volume pc-ASPECTS≤8 was independently associated with poor outcome (OR 9.3 95%CI 2.2–41; p = 0.003, adjusted for age and clinical severity). Inter-rater agreement was substantial for cerebral blood volume pc-ASPECTS (intraclass correlation coefficient 0.82 95%CI 0.71–0.90 versus 0.67 for CTA-SI 95%CI 0.43–0.81). Conclusions: Cerebral blood volume pc-ASPECTS may identify VBAO patients at higher risk of disability.