Parole chiave: Endothelial Factors, Brain Perfusion, Intracranial Circulation,
*** IBB - CNR ***
Background: Among the factors contributing to brain damage in Multiple Sclerosis (MS), scientific<br>evidences indicate ischemic changes, venous outflow abnormalities and accumulation of proinflammatory<br>and neurotoxic substances.<br>Objectives: This project aims at acquiring new know ledge about the association of determinants of<br>brain perfusion in patients w ith MS and neurodegenerative diseases such as Amyotrophic Lateral<br>Sclerosis (ALS), combining Magnetic Resonance (MR) and Ultrasound (US) imaging of the brain and<br>intracranial and extracranial circulation, and endothelial factors.<br>Methods: 300 MS patients, 50 ALS patients, and 300 healthy subjects (HS) w ill be recruited over 3<br>years. To assess the vascular genetic susceptibility, serum levels of homocystein and endothelial<br>factors w ill be assayed, as w ell as the association betw een the C677T polymorphism of methylentetrahydrofolate<br>reductase (MTHFR), informative SNPs in VEGF-A, Endothelin 1 and HIF1A genes<br>and micro and macro vascular abnormalities in MS and ALS. With MR, w e w ill assess the arterial<br>inflow and mean transit time using brain Perfusion Weighted Imaging (PWI), the state of the deep<br>intracranial veins using Susceptibility Weighted Imaging (SWI), and measure iron deposits in the<br>basal ganglia using dedicated softw are. Extracranial and transcranial color-Doppler US w ith time<br>intensity curve analysis w as used to quantitatively evaluate cerebral inflow and outflow parameters<br>and cerebral perfusion.<br>Results: In the first year w e recruited 228 MS patients, 33 ALS patients and 67 HS. Homocystein<br>levels (HL) w ere assessed in 132 patients, VEGF-A in 50 patients and in 25 HS. Median HL w ere<br>similar in MS and ALS patients (13.2 vs 16.0, µmol/L, p=0.2). Higher-than-normal HL w ere found in<br>32.2% of MS (CI 24-41%) and 66.7 % of ALS patients (CI 30-92%), but not significantly different in<br>the tw o groups (p= 0.08). Instead, median HL w ere significantly higher in males w ith MS compared<br>to females (17.3 vs 13.9 µmol/L, p< 0.001) .VEGF-A values tended to be higher in MS patients vs HS<br>(251.7 vs 145.7 U/mL, p=0,4). 101 patients (78 RR, 2 PP, 11 SPand 10 ALS) underw ent contrastenhanced<br>brain MR , and 68 patients (54 RR, 1 PP, 10 SPand 3 ALS) underw ent US evaluation.<br>Conclusions: Combining different imaging modalities and laboratory analysis may provide new<br>insights into the vascular aspects of MS pathogenesis. These preliminary results favor an altered<br>vascular profile in MS and ALS patients. Definitive results w ill be available at project termination in<br>2016.
15 Records (9 escludendo Abstract e Conferenze). Impact factor totale: 43.227 (28.911 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 49.736 (32.803 escludendo Abstract e Conferenze).