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Background: Multiple sclerosis (MS) studies suggest greater cardiovascular disease burden and disturbances in the cholesterol pathways. The potential impact of oxidized cholesterol molecules on MS is emerging., Objective: To determine the relationship between multiple oxysterol molecules and atherosclerosis burden in MS patients., Materials and Methods: A total of 99 MS patients (61 relapsing-remitting MS(RRMS) and 38 progressive MS (PMS)) patients and 38 healthy controls (HCs) underwent magnetic resonance angiography (MRA) and the cross-sectional area (CSA) of the common carotid artery (CCA) was determined at three different levels before the bifurcation (C7, C6 and C5). Additionally, an echo-color Doppler ultrasound was performed and measures of blood flow velocities were derived. Blood samples acquired at the time of the imaging examinations were analyzed and 24-, 25-, 27-hydroxycholesterol (24HC, 25HC, 27HC) and 7-ketocholesterol (7KC) were quantified in ng/mL RESULTS: In the MS patients, higher levels of 24HC were significantly associated with smaller CCA CSA measured at all three cervical levels (r=-0.201, p = 0.046; r=-0.228, p = 0.023, and r=-0.215, p = 0.032, for C7, C6 and C5, respectively). These associations were driven by the RRMS group only (r=-0.407, p = 0.002 for C7; r=-0.414, p = 0.002, for C6; and r=-0.368, p = 0.006 for C5). No associations were seen in the HCs. Despite adjusting for the significant age effect (B = 0.445, p = 0.004), higher 24HC levels were independently associated with smaller CCA CSA (B=-0.20, p = 0.045). 24HC was additionally associated with greater time-averaged and peak diastolic CCA velocities. RRMS patients treated with potent anti-inflammatory therapies had lower oxysterol levels (p = 0.019)., Conclusion: Greater 24HC levels are associated with smaller CSA CCA and greater flow velocities in RRMS patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We assessed cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) within gray matter (GM), normal appearing white matter (NAWM) and white matter (WM) lesions in a group of multiple sclerosis (MS) patients. Furthermore, correlations between CBF, CVR and age were investigated. 31 MS patients and 25 healthy controls (HC) were examined on a 1.5 T MRI scanner, using pseudo-continuous arterial spin labeling MRI. MS vs HC CBF and CVR differences were assessed in GM regions of interest (i.e. resting state networks and vascular territories), and within WM. Correlations between CBF/CVR and age were then computed for MS and HC groups. Whereas no significant CBF and CVR differences were observed between MS and HC in any of the considered brain areas, significantly lower CBF was found in WM lesions with respect to NAWM (p < 0.001) in MS patients. Furthermore, CVR was significantly correlated with age in HC, but not in MS patients. The relatively low-grade of inflammation of our MS cohort may be associated with the observed lack of significant CVR differences between MS patients and HC. The loss of correlation between CVR and age in the MS group suggests that CVR may be influenced by MS-related factors.

Background: Grey Matter (GM) atrophy has been extensively described in Multiple Sclerosis (MS) patients, while cerebral hypoperfusion has been less consistently reported. Since hypoperfusion might be related to atrophy, we evaluated the presence of both damages., Objective: We aimed to assess if the regions of altered perfusion and atrophy overlapped with one another and if the two parameters were locally related., Method: 3D-T1 weighted and arterial spin labelling sequences were acquired using a 1.5T Magnetic Resonance Imaging scanner from 26 relapsing remitting MS patients and 26 Healthy Controls (HC). GM volume and Cerebral Blood Flow (CBF) differences and their correlation were tested with a voxel-wise approach., Results: MS patients (41.4±12.5 years; 14 females) had a median [25th-75th percentile range] Expanded Disability Status Scale of 1.0[1.0-2.4] and a median [25th-75th percentile range] disease duration of 8.0 [4.0-16.5] years. HC were age- and sex-matched (43.9±17.4 years; 11 females). GM atrophy was detected for MS group in the right parahippocampal gyrus, thalami and left caudate (pFWE≤0.05). Areas of significant (after family-wise error -FWE- correction for multiple comparisons) (pFWE≤0.05) hypoperfusion were found for MS in the anterior cingulate and paracingulate gyri, supplementary motor cortex, precentral and superior frontal gyrus. GM volume and CBF showed a significant correlation (pFWE≤0.05) in the right lateral occipital cortex and precuneus in the MS group., Conclusions: GM atrophy and hypoperfusion in MS were located in different areas. Perfusion estimate might be used as a further marker of tissue damage, in addition to GM volume., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Hyperlipidemia is associated with worse clinical and radiological outcomes in persons with multiple sclerosis (PwMS) and studies show greater MS extracranial arterial vessel pathology. Objective: The aim of this study was to determine the effect of lipid profile measures on extracranial arterial vessels in PwMS and healthy controls (HCs). Methods: Non-contrast magnetic resonance angiography was conducted on 104 PwMS and 41 HCs. The cross-sectional area (CSA) of the common carotid artery (CCA) and vertebral artery (VA) was measured using a semi-automated edge-detection/contouring method at cervical levels C4-C7. The lipid profile was obtained at the time of the scan. Repeated measures analyses adjusted for age, gender, and body mass index were used. Results: In PwMS, age was associated with CCA CSA (F = 7.65, η2 = 0.083, p = 0.007) and lipoprotein(a) [Lp(a)] with VA CSA (F = 13.4, η2 = 0.13, p < 0.001). These associations were not present in HCs. PwMS with Lp(a) ≥30 and ≥50 mg/dL, and within the highest Lp(a) quartile had significantly larger CCA and VA when compared to those with lower Lp(a) threshold values. Total cholesterol and low- and high-density lipoprotein cholesterol were not associated with CCA or VA CSA. Conclusions: Lp(a) levels are associated with CSA of major extracranial arterial vessels in PwMS but not in HCs. The clinical and pathological significance of these associations, if any, remains unknown. [ABSTRACT FROM AUTHOR]