Atorvastatin decreases high-sensitivity C-reactive protein in multiple sclerosis.

The anti-inflammatory potential of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, as reflected by modulation of C-reactive protein (CRP), might be beneficial in the treatment of patients with multiple sclerosis (MS). We evaluated serum levels of high-sensitivity (hs)-CRP in relapsing-remitting MS patients receiving interferon-beta 1b and atorvastatin as add-on therapy. This study shows that interferon-beta treatment is associated with increased serum levels of hs-CRP in MS patients (P<0.01). In contrast, when atorvastatin is added to interferon-beta, hs-CRP serum levels decrease to the normal range (P<0.05), indicating an anti-inflammatory action of atorvastatin in MS. However, whether add-on treatment with atorvastatin modifies the course of MS remains to be investigated.

Atorvastatin does not alter serum levels of sCD95 and sCD95L in multiple sclerosis.

Elimination of autoreactive T cells by apoptosis is critical for restricting immune responses to self-antigens. An errant lytic interaction between the CD95 death receptor and its ligand CD95L is presumed to be involved in the pathogenesis of multiple sclerosis (MS). Statins are promising agents for the treatment of MS and were shown to modulate levels of soluble death receptors. Here, we evaluated the in vivo effects by interferon (IFN)-beta and atorvastatin on soluble CD95 (sCD95) and sCD95L in serum of patients with MS. Concentrations of sCD95 and sCD95L did not show any differences between MS and healthy control subjects. In patients with MS, treatment with IFN-beta increased serum levels of sCD95 and sCD95L significantly (P < 0.01 and P < 0.05 respectively). Addition of atorvastatin to IFN-beta did not alter serum levels of sCD95 and sCD95L significantly. Our study suggests that atorvastatin does not affect IFN-beta-induced increases of the soluble death receptors in the serum of patients with MS.

Acute partial transverse myelitis: risk factors for conversion to multiple sclerosis.

Acute partial transverse myelitis (APTM) may be the first clinical manifestation of multiple sclerosis (MS), of relapsing myelitis, or remain a monophasic event. Identification of risk factors associated with relapse or conversion to MS is important, as prognostic information might help to guide management. The objective of this study was to define clinical, laboratory and neuroimaging factors in patients with first-ever APTM that predict relapses or conversion to MS. We identified 73 patients with a first-ever APTM admitted to our institution from January 1999 to June 2005. The follow-up time ranged from 12 to 90 months (mean follow-up 46 months). Patient demographics, clinical impairment at onset and after 3 months, ancillary tests including cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), evoked potentials, recurrent and new symptoms and signs during follow-up were analysed. APTM remained a monophasic event in 35 patients (47.9%), conversion to MS occurred in 32 (43.8%) and recurred as relapsing myelitis in six patients (8.2%). According to univariate analysis, a family history of MS (P = 0.02), higher expanded disability status scale (EDSS) at onset (P = 0.03) and lesions on brain MRI (P = 0.03) were predictive factors for conversion to MS. CSF-specific oligoclonal bands (P = 0.04) or abnormal IgG-index (P = 0.04) were associated with increased risk for MS as well. In patients with a first-ever APTM, a family history of MS, high EDSS at presentation, lesions on brain MRI, CSF-specific oligoclonal bands or abnormal IgG-index may indicate an increased risk for conversion to MS.

Anti-myelin antibodies in clinically isolated syndrome indicate the risk of multiple sclerosis in a Swiss cohort.

OBJECTIVES: In patients with a clinically isolated syndrome (CIS), the time interval to convert to clinically definite multiple sclerosis (CDMS) is highly variable. Individual and geographical prognostic factors remain to be determined. Whether anti-myelin antibodies may predict the risk of conversion to CDMS in Swiss CIS patients of the canton Berne was the subject of the study. METHODS: Anti-myelin oligodendrocyte glycoprotein and anti-myelin basic protein antibodies were determined prospectively in patients admitted to our department. RESULTS: After a mean follow-up of 12 months, none of nine antibody-negative, but 22 of 30 antibody-positive patients had progressed to CDMS. Beta-Interferon treatment delayed the time to conversion from a mean of 7.4 to 10.9 months. CONCLUSIONS: In a Swiss cohort, antibody-negative CIS patients have a favorable short-term prognosis, and antibody-positive patients benefit from early treatment.

[Uric acid and multiple sclerosis]. / Schützt Harnsäure vor Multipler Sklerose?

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Its etiology is not known, but it is well established that auto-reactive T-cells and monocytes play an important pathogenetic role. Experimental allergic encephalomyelitis (EAE) of mice serves as disease model for MS. In both EAE and MS inflammatory cells produce nitric oxide and its oxidizing congeners such as peroxynitrite. Peroxynitrite and other reactive nitrogen oxide species exert a toxic effect on neurons, axons and glia cells and enhance apoptosis. In addition, they increase the blood-CNS-barrier permeability and can therefore promote invasion of inflammatory cells into the CNS. On the other hand, uric acid, a peroxynitrite scavenger inhibits blood-CNS-barrier permeability changes, CNS inflammation and tissue damage in EAE. Epidemiological studies have shown that MS and gout are almost mutually exclusive diseases. Uric acid levels in MS patients are lower than in controls and in patients with active disease lower than in MS patients in remission. Inosine, a uric acid precursor, can be used to raise uric acid levels in serum and may provide some benefit in MS patients. A small study of ten patients with progressive MS has demonstrated some improved function in three of them and no sign of progression or relapse in the other. However, this study does not justify a recommendation for use of inosine in MS patients yet. At present, uric acid can solely be regarded as a marker of disease activity in MS. In addition, the current knowledge of uric acid and MS supports hypotheses which predict a positive effect of radical scavengers in MS.

The human DIMINUTO/DWARF1 homolog seladin-1 confers resistance to Alzheimer's disease-associated neurodegeneration and oxidative stress.

In Alzheimer's disease (AD) brains, selected populations of neurons degenerate heavily, whereas others are frequently spared from degeneration. To address the cellular basis for this selective vulnerability of neurons in distinct brain regions, we compared gene expression between the severely affected inferior temporal lobes and the mostly unaffected fronto-parietal cortices by using an mRNA differential display. We identified seladin-1, a novel gene, which was downregulated in large pyramidal neurons in vulnerable regions in AD but not control brains. Seladin-1 is a human homolog of the DIMINUTO/DWARF1 gene described in plants and Caenorhabditis elegans. Its sequence shares similarities with flavin-adenin-dinucleotide (FAD)-dependent oxidoreductases. In human control brain, seladin-1 was highly expressed in almost all neurons. In PC12 cell clones that were selected for resistance against AD-associated amyloid-beta peptide (Abeta)-induced toxicity, both mRNA and protein levels of seladin-1 were approximately threefold higher as compared with the non-resistant wild-type cells. Functional expression of seladin-1 in human neuroglioma H4 cells resulted in the inhibition of caspase 3 activation after either Abeta-mediated toxicity or oxidative stress and protected the cells from apoptotic cell death. In apoptotic cells, however, endogenous seladin-1 was cleaved to a 40 kDa derivative in a caspase-dependent manner. These results establish that seladin-1 is an important factor for the protection of cells against Abeta toxicity and oxidative stress, and they suggest that seladin-1 may be involved in the regulation of cell survival and death. Decreased expression of seladin-1 in specific neurons may be a cause for selective vulnerability in AD.