For more than 30 years Corticosteroids have been used to manage MS Relapses, but there is still considerable variation in how and when they are used.

Corticosteroids, such as Methyl-prednisolone, commonly used by MS patients, are related to Cortisol, a hormone which occurs naturally in the body. Although they can be effective in hastening recovery from a relapse they do not in any way ‘fix’ the problem and prevent further episodes of MS from occurring.

During an MS relapse there is a breaking down of the ‘blood brain barrier’ (BBB), so that harmful substances from the bloodstream can cross this barrier and reach the brain and spinal cord. The steroids are thought to help stabilise the BBB and help close up this leaking. They also reduce the inflammation in the central nervous system so allowing the brain signals to be transmitted for ‘normal’ body function again. Corticosteroids are also immunosuppressive. This means that they reduce the activity of your immune system. A healthy immune system helps defend your body against bacteria, viruses, and cancer.

However with autoimmune diseases the immune system goes starts attacking it’s own organs or tissue, in the case of MS this is the myelin sheath which coats the nerves cell fibres in the brain and spinal cord. In these diseases, Corticosteroids can help by decreasing the harmful autoimmune activity. However, they also decrease the body's helpful immune activity, which can increases susceptibility to infection and interfere with the healing process.

During an infusion some people experience a metallic taste in their mouth. Other short-term side affects can include increased heart rate, hot flushes, a red face, sleeping problems, mood swings or even a sense of euphoria.

The long-term use of Corticosteroids can be very harmful, disrupting and weakening the immune system, with the danger of developing Osteoporosis (brittle bone disease). Other long-term side effect are weight gain, ‘moon’ face’, muscle wastage, Diabetes, bone fractures, acne, skin bruising, cataracts, peptic ulcers and wounds taking longer to heal.

For this reason doctors generally do not administer them that frequently and even then only after a ‘major’ relapse. The majority of UK Neurologists will administer them intravenously (1g daily for 3 days), but they may also be taken orally.

Scientists are closing in on the solution to a persistent medical puzzle: why do high doses of cortisone (widely prescribed for asthma, rheumatoid arthritis, Multiple Sclerosis, and other inflammatory and autoimmune conditions) weaken bones?

Through studies of mice, researchers at Washington University School of Medicine in St. Louis have now identified osteoclasts, cells that dismantle old bone, as the essential link between osteoporosis and cortisone. As scientists flesh out the molecular-level details of this connection, they may be able to identify targets for therapy to prevent cortisone’s damaging side effects on bone.

“High-dose cortisone is the second most common cause of osteoporosis, and we currently have no real treatment for this serious side effect,” says senior author Steven L. Teitelbaum, M.D., Messing Professor of Pathology and Immunology. “Given how frequently these drugs are used to treat many different conditions, that’s a major clinical problem.”

Cortisone is a steroid produced naturally by the adrenal gland and synthesized by a number of pharmaceutical companies for clinical use. The drug is also used to treat lupus, multiple sclerosis, and chronic obstructive pulmonary disease, and it is prescribed to transplant patients to prevent rejection of transplanted organs.

Earlier attempts to identify the connection between bone loss and cortisone produced seemingly contradictory results. In lab animal experiments, researchers found cortisone caused bone-building osteoblast cells to self-destruct, suggesting that cortisone disrupts the body’s ability to form new bone after it is naturally dismantled by osteoclasts. However, experiments in the test tube also showed cortisone stimulates bone formation.

Teitelbaum identified a new opportunity for exploring the conundrum while at a lecture by Washington University colleague Louis J. Muglia, M.D., Ph.D., director of pediatric endocrinology at St. Louis Children’s Hospital. Muglia’s group studies the health effects of stress, many of which are mediated by cortisone. To aid his research, Muglia developed a line of genetically modified mice where receptors for cortisone, which are found throughout the body, could be selectively eliminated in individual cell types.

By crossbreeding their genetically modified mouse lines, researchers produced a line of mice whose bone-dismantling osteoclasts lacked cortisone receptors. When researchers gave cortisone to these mice, the bone-weakening effects of the drugs were blocked.

In addition, scientists found that cortisone inhibits the ability of osteoclasts to dismantle old bone in genetically normal mice. This blockage might seem to leave bones free to retain their strength, but with the regular skeletal renewal process stopped, bones will weaken dramatically from aging and stress. Dampening of osteoclast activity may also cause a chain reaction that slows activity of bone-building osteoblasts.

“We now have an idea of what’s happening from a viewpoint of 1,000 feet up or so,” says Teitelbaum, comparing the new insight to sighting a highway from an airplane window. “Now we’ll start looking more closely at the molecular mechanisms involved to see if we can generate therapeutic targets.”

Source: Multiple Sclerosis All About Me (12/03/08)

OBJECTIVES: To determine the efficacy and safety of long-term corticosteroid use in MS.

SEARCH STRATEGY: We searched the following bibliographic databases: CENTRAL (Issue 1, 2007), MEDLINE (1966 to February 2007) and EMBASE (1980 to February 2007). In an effort to identify further published, unpublished and ongoing trials we searched reference lists and contacted trial authors and one pharmaceutical company.

SELECTION CRITERIA: We considered controlled, randomised trials (RCTs), with or without blinding, of long term treatment (i.e. longer than 6 months) of any type of corticosteroid in MS, irrespective of disease course.

DATA COLLECTION AND ANALYSIS: Reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information.

MAIN RESULTS: Three trials, all classified at high risk of bias, contributed to this review (Miller 1961; BPSM 1995; Zivadinov 2001) resulting in a total of 183 participants (91 treated). Corticosteroid therapy did not reduce the risk of being worse at the end of follow-up (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.26 to 1.02) but there was a substantial heterogeneity between studies (I(2): 78.4%). I. v. periodic high dose methylprednisolone (MP) was associated with a significant reduction in the risk of disability progression at 5 years in relapsing-remitting (RR) MS (OR 0.26, 95% CI 0.10 to 0.66), while oral continuous low dose prednisolone was not associated with any risk reduction in disability progression at 18 months (OR 1.23, 95% CI 0.43 to 3.56). Risk of experiencing at least one exacerbation at end of follow-up was not significantly reduced with corticosteroid treatment (OR 0.36; 95% CI 0.10 to 1.25).Only one study recorded adverse events: in one patient i. v. MP was discontinued after the fourth pulse when he developed acute glomerulonephritis; a second patient was removed from the study after the fifth i. v. MP pulse because of severe osteoporosis.

AUTHORS' CONCLUSIONS: There is no enough evidence that long-term corticosteroid treatment delays progression of long term disability in patients with MS. Since one study at high risk of bias showed that the administration of pulsed high dose i. v. MP is associated with a significant reduction in the risk of long term disability progression in patients with RR MS, an adequately powered, high quality RCT is needed to investigate this finding.

Ciccone A, Beretta S, Brusaferri F, Galea I, Protti A, Spreafico C.

Source: PubMed PMID: 18254098 (13/02/08)

This study concerning steroids & blood cells was conducted at the
Neuroimmunology Unit, Medical School, University of Tampere, Tampere, Finland.

Summary:
Therapy of acute exacerbations of multiple sclerosis with high-dose intravenous methylprednisolone inhibits the potential transmigration of CCR5-expressing CD4(+) and CD8(+) blood cells into the central nervous system. This is consistent with the short-term beneficial effect of IVMP in acute exacerbation of MS.

Objectives:
Therapy of acute exacerbations of multiple sclerosis with high-dose intravenous methylprednisolone has shortened the recovery period after relapses, but the mechanisms responsible for the beneficial effects of intravenous methylprednisolone in attacks have not been clearly established.

Our purpose was to analyze the effect of IVMP on the expression of chemokine receptor 5 (CCR5) protein in blood in acute MS exacerbation.

Materials and methods: 
Blood samples were collected from 10 patients with an acute MS exacerbation and the levels of CCR5 on CD4(+) and CD8(+) T cells and CD14(+) monocytes were analyzed by using flow cytometry before intravenous methylprednisolone, 24 h, 1 and 3 weeks after commencement of treatment.

Results:
During the 3-week period the percentages of CCR5-expressing CD4(+) T cells and CD8(+) T cells tended to decrease, but the effect did not reach statistical significance. No marked changes were found in the percentage of CCR5-expressing CD14(+) cells.

Conclusions:
A tendency to a reduction of CCR5-expressing CD4(+) and CD8(+) blood cells induced by intravenous methylprednisolone suggests inhibition of their potential to transmigrate into the central nervous system, which is consistent with the short-term beneficial effect of intravenous methylprednisolone in acute exacerbation of MS.

Source: pubmed.gov

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