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Background: Natalizumab therapy reduces inflammation and degeneration of the CNS in relapsing-remitting multiple sclerosis (RRMS). In cerebrospinal fluid (CSF) the concentration of 24S-hydroxycholesterol (24OHC) reflect neurodegeneration, whereas 27-hydroxycholesterol (27OHC) is dependent on the integrity of the blood-brain barrier (BBB)., Objective: To measure the impact from natalizumab treatment on 24OHC and 27OHC concentrations in serum and CSF of RRMS., Methods: In serum and CSF obtained from 31 patients before and following 12 months of natalizumab treatment, 24OHC and 27OHC were analyzed by isotope-dilution mass spectrometry., Results: Natalizumab treatment reduced CSF-24OHC concentrations (p=0.002), CSF-27OHC concentrations (p=0.01) and serum-24OHC concentrations (p=0.029). There was no significant effect of the treatment on serum-27OHC concentrations. Serum concentrations of 24OHC correlated with Symbol Digit Modalities Test scores before (r=0.5, p=0.007) and after natalizumab treatment (r=0.403, p=0.033)., Conclusions: We showed for the first time that natalizumab treatment of RRMS reduced the concentrations of 24- and 27OHC in CSF, indicating reduced neurodegeneration and improved integrity of the BBB, respectively. Our results imply a role for serum 24OHC as a biomarker of cognition (visuo-spatial ability and processing speed) in RRMS., (Copyright © 2015 Elsevier B.V. All rights reserved.)

To investigate whether multiple sclerosis (MS) patients with and without cerebrospinal fluid (CSF) oligoclonal immunoglobulin G bands (OCB) differ in brain atrophy. Twenty-eight OCB-negative and thirty-five OCB-positive patients were included. Larger volumes of total CSF and white matter (WM) lesions; smaller gray matter (GM) volume in the basal ganglia, diencephalon, cerebellum, and hippocampus; and smaller WM volume in corpus callosum, periventricular-deep WM, brainstem, and cerebellum, were observed in OCB-positives. OCB-negative patients, known to differ genetically from OCB-positives, are characterized by less global and regional brain atrophy. This finding supports the notion that OCB-negative MS patients may represent a clinically relevant MS subgroup., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objectives: The concentration in plasma of the brain-specific cholesterol metabolite cerebrosterol has been proposed as a biomarker of neurodegeneration in multiple sclerosis (MS) and other neurological diseases. It is unknown, however, which pathophysiological process in MS best accounts for variations in plasma cerebrosterol., Patients and Methods: In this study, we related plasma cerebrosterol concentrations in 46 MS patients - 27 with a relapsing-remitting (RR) disease course and 19 with a primary progressive (PP) course - to three conventional magnetic resonance imaging measures: on T(1)-weighted brain scans, volume of gadolinium-enhanced lesions (a marker of active inflammation) and hypointense lesions (a marker of edema or axonal loss) and on T(2)-weighted scans, volume of hyperintense lesions (a marker of disease extent)., Results: By multiple-regression analysis, we uncovered negative correlations between the cerebrosterol-cholesterol ratio in plasma and both age at sampling (beta=-0.35 and p=0.079 in RRMS; beta=-0.76 and p=0.006 in PPMS) and volume of T(2)-weighted lesions (beta=-0.52 and p=0.078 in RRMS; beta=-0.50 and p=0.247 in PPMS)., Conclusion: We hypothesize that decreases in plasma cerebrosterol may reflect the total spatiotemporal burden of MS-the cumulative effects of its dissemination in space and its duration in time.