The Multiple Sclerosis Severity Score (MSSS) is a powerful method for comparing disease progression using single assessment data. The Global MSSS can be used as a reference table for future disability comparisons. While useful for comparing groups of patients, disease fluctuation precludes its use as a predictor of future disability in an individual.

CTLA-4, expressed mainly on activated T cells, helps maintain, through its inhibitory function, immune-system homeostasis. Polymorphisms in the CTLA-4 gene (CTLA4) are known to be important in several autoimmune diseases, including multiple sclerosis (MS). Here, we have performed genotyping for CTLA4 polymorphisms, and investigated expression by peripheral blood mononuclear cells of CTLA-4 mRNA and protein, in patients with MS and myasthenia gravis and in healthy controls. Expression levels for mRNA and protein were similar in the patient and control groups; however, there was a clear relationship between genotype and CTLA-4 expression. Specifically, individuals carrying thymine at position -318 of the CTLA4 promoter (T(-318)) and homozygous for adenine at position 49 in exon 1 showed significantly increased expression both of cell-surface CTLA-4 after cellular stimulation and of CTLA-4 mRNA in non-stimulated cells. The association was seen most clearly for unsorted CD3(+) cells and was absent in the CD8(+) subset. The T(-318) allele has been shown to be negatively associated with susceptibility to MS in an earlier study by our group. Thus, we propose that the susceptibility-influencing role of CTLA4 in MS may be related to genotypically conditioned promoter function, whereby high gene expression may decrease the risk of disease.

This study assessed the cost to society of multiple sclerosis (MS) in Sweden in 1998. The cost-of-illness method, based on the human capital theory, was used as the theoretical framework. The study used a cross-sectional approach, in which resource utilization data and quality-of-life data (utilities) were collected at a single time point. The total cost of MS was estimated at 4868 MSEK, or 586 MEUR, giving an annual cost of 442 500 SEK, or 53 250 EUR, per patient (1USD = 9.73 SEK, 1 EUR = 8.31 SEK, as of 21 September 2000). Direct costs accounted for about 67% of total cost, and they were dominated by the cost of personal assistants and drugs. Indirect costs (loss of production) accounted for about 33% of total costs. To these economic costs, intangible costs of 2702 MSEK (325 MEUR) should be added as well. Direct, indirect and informal care costs all rose significantly with increased disability and were higher during a relapse. Quality of life declined substantially with increased disability and was lower during a relapse. Multiple sclerosis was found to be associated with much higher costs to society than has been ascertained by former studies. The study also revealed a strong correlation between severity of the disease and quality of life. These results are crucial for further studies on the cost-effectiveness of new treatments aimed at preventing relapses and reducing progression of the disease.

The side chain oxidized oxysterol 24 S -hydroxycholesterol (24-OH-chol) is formed almost exclusively in the brain, and there is a continuous passage of this oxysterol through the circulation to the liver. 27-Hydroxycholesterol (27-OH-chol) is produced in most organs and is also taken up by the liver. The 27-OH-chol-24-OH-chol ratio is about 0.1 in the brain and about 2 in the circulation. This ratio was found to be about 0.4 in cerebrospinal fluid (CSF) of asymptomatic patients, consistent with a major contribution from the circulation in the case of 27-OH-chol. In accordance with this, we demonstrated a significant flux of deuterium labeled 27-OH-chol from plasma to the CSF in a healthy volunteer. Patients with a defective blood-brain barrier were found to have markedly increased absolute levels (up to 10-fold) of both 27-OH-chol and 24-OH-chol in CSF, with a ratio between the two sterols reaching up to 2. There was a significant positive correlation between the levels of both oxysterols in CSF and the albumin CSF -albumin plasma ratio. The 27-OH-chol CSF -24-OH-chol CSF ratio was found to be about normal in patients with active multiple sclerosis and significantly increased in patients with meningitis, polyneuropathy, or hemorrhages. 24 S -Hydroxycholesterol (24-OH-chol) is almost exclusively formed in the brain, where it is present in greater amounts than in any other organ (8.6-15.1 ng/mg wet weight)(1). There is a daily flux of about 7 mg of this oxysterol from the brain to the circulation, with the majority of this efflux apparently occurring as direct transport across the blood-brain barrier (BBB) (2). It has been estimated that less than 1% of the 24-OH-chol produced by the brain is transported to the circulation via passage through the cerebrospinal fluid (CSF) (1). The enzyme responsible for the 24 S -hydroxylation of cholesterol is a member of the cytochrome P450 superfamily (designated CYP46), and has been mainly localized to neurons (3). Assuming that the expression of this enzyme across the neuronal population is relatively stable, any loss of these cells would result in a decreased production of this oxysterol. In accordance with this, reduced levels of plasma 24-OHchol have been observed in connection with several chronic neurological conditions known to affect the number of neurons (4).In contrast to the above oxysterol, 27-hydroxycholesterol (27-OH-chol) is formed in most cells, and there is a constant flux of this oxysterol from extrahaepatic tissues to the liver (5, 6). A noteworthy exception is the brain (no net flux has been observed from this organ) and the levels of 27-OH-chol are about 10-fold lower than those of 24-OH-chol (1). However, the plasma levels of 27-OH-chol are about twice those of 24-OH-chol.The term BBB is commonly used to describe a whole range of mechanisms that regulate and protect the internal environment in the brain (7-11). More specifically, this term is used to indicate a relative restriction of the entry of the plasma proteins into the brain. This barrier a...