Plasma cerebrosterol and magnetic resonance imaging measures in multiple sclerosis.

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.

Immunopathogenesis and immunotherapeutic approaches in multiple sclerosis.

Multiple sclerosis is an organ-specific autoimmune disease, characterized pathologically by cell-mediated inflammation, demyelination and variable degrees of axonal loss. Although inflammation is considered central to the pathogenesis of multiple sclerosis, to date, the only licensed and hence widely used multiple sclerosis immunotherapies are interferon-beta, glatiramer acetate and mitoxantrone. This review discusses the immunopathogenesis of multiple sclerosis, focusing on a number of emerging immunotherapies. A number of new approaches likely to manipulate the immunopathogenesis of multiple sclerosis and which may ultimately allow for the development of more effective immunotherapy are also highlighted.

Serum S100B in primary progressive multiple sclerosis patients treated with interferon-beta-1a.

S100B belongs to a family of calcium-binding proteins implicated in intracellular and extracellular regulatory activities. This study of serum S100B in primary progressive multiple sclerosis (PPMS) is based on data obtained from a randomized, controlled trial of Interferon beta-1a in subjects with PPMS. The key questions were whether S100B levels were associated with either disability or MRI findings in primary progressive MS and whether Interferon beta-1a has an effect on their S100B levels. Serial serum S100B levels were measured using an ELISA method. The results demonstrated that serum S100B is not related to either disease progression or MRI findings in subjects with primary progressive MS given Interferon beta-1a. Furthermore there is no correlation between S100B levels and the primary and secondary outcome measures.