MULTIPLE SCLEROSIS

How do steroids work?

The mechanisms by which steroids work  in Ms are not fully understood. However, there are several properties of steroids that make them effective in hastening recovery from MS relapses.

In an MS relapse, there is a breaking down of the `blood brain barrier` that normally blocks chemical imbalances and harmful substances from the bloodstream reaching the brain and spinal cord.For more than 30 years, steroids have been the mainstay in the management of MS relapses. However there are no hard and fast rules about when and how to use them, and there is considerable variation in the ways steroids are prescribed.

Probably the most significant property of steroids in treating MS relapses is their ability to help stabilize the blood brain barrier and help close the `leaking`.

In an MS relapse, there is also inflammation and the loss of protective myelin around the nerve fibers of the central nervous system. Steroids can dampen down the immune system’s attack on its own myelin and reduce inflammation. Steroids are active at all stages of the inflammatory process and reduce the initial heat and swelling, as well as interfering with the processes that support chronic (long-lasting) inflammation.

 FROM ONE MS MATTERS READER

`Steroids have helped me recover from MS attacks numerous times,`  says one MS Matters reader who has had MS since 1991. `I ask my neurologist or GP for them when I have a severe attack because I’ve found the drug so beneficial. The attack, which would otherwise last for months, is stopped and my symptoms then start to improve. The treatment itself and the immediate side effects are not very pleasant but for me they are preferable to having to endure the effects of the attack. To me, steroids make the difference between seeing or not seeing, walking or not walking.`

Steroids can`t  provide instant recovery. While steroids can speed up recovery from relapses, they don`t influence the degree of recovery. There is no evidence to suggest that steroids slow progression of MS or improve symptoms over a long period of time.

ORAL -  VERSUS - INTRAVENOUS STEROIDS

`It is clear that the majority of relapses in MS patients never come to the attention of the specialist,`  says Dr David Barnes of St Peter`s Hospital, Chertsey, Surrey. `Many patients simply do not mention less severe attacks, or they contact their GPs who give them an oral course of steroids without referral to the local neurologist.`

When steroids are prescribed, however, there are wide variations in both the way steroids are administered and the dosages given.

The choice of steroids to treat a relapse lies mainly between intravenous methylpednisolone (ivMP) or oral prednisolone (OP). Dexamethasone is also used (and generally given orally and at about one-tenth the dose of OP). The first form of steroid therapy to be widely used in MS – the steroid ACTH – was felt by  the mid-1980s to be less predictable and no more effective than other steroids and it was therefore removed from general use.

Surveys have shown that the majority of UK neurologists will initially chose intravenous administration (ivMP) for severe MS relapses but that might be a preference based on instinct and habit rather than sound scientific evidence.

Two clinical trials in the mid-to late-90s provide at least food for thought. In one of the  trials, reported in  the Lancet (1997; 349: 902-6), the results showed that by using oral methylprednisolone at a dose as high as intravenous methylprednisolone, there was no difference between the treatments. The choice of steroid was shown to be of less importance, as long as   the chosen treatment was given in adequate doses. The trials involved relatively small numbers of patients and cannot be considered to prove conclusively that oral steroid is as effective in a relapse as an intravenous steroid. However if  there is no clear advantage of  the intravenous regimen, then the researchers conclude that it would be preferable to prescribe oral rather than intravenous steroids for acute relapses in MS for patient convenience, safety as well as cost.

PRACTICAL GUIDELINES FOR USING STEROIDS

Steroids should always be taken under a doctor`s supervision and it is not good practice  to prescribe steroids indiscriminately for MS relapse.

`When considering which relapses should be treated  with steroids, it isn`t essential to consider how often steroids have been given   in the past,` says Dr Barnes. `However, in general, it is sensible to limit the number of courses, if possible, to three a  year.`

`The decision to take steroids should be at least partly dictated by how severe the attack is and by the amount of disability and handicap it produces,` says Dr Barnes. This is often an individual thing. What will be disabling for one individual may be an inconvenience for another and  non-disabling attacks will usually recover satisfactorily without treatment.

Another thing to consider before prescribing steroids is the type of attack. In optic neuritis, steroids are generally recommended only if the loss of vision, inflammation and pain are severe. Again, opinion is divided as to whether steroids can actually improve the outcome of severe attacks of optic neuritis but recent data appears to confirm that steroids do not influence the degree of recovery. In milder cases, the general policy is to `sit it out`. Steroids should also be considered for any attack affecting the cerebellar function of the brain, for example, a loss of co-ordination and balance, or problems  with speech.

When there is no hard data about when to take steroids and when not to, there are bound to be difficulties. An MS Matters reader writes, `my neurologist still dislikes me having any say or involvement in how I am treated. The constant  “mother knows best” attitude is very tiresome. I know that for me, steroid treatment has worked well. Why do I face a constant battle to have my opinion considered carefully to have a treatment given? `

`To some extent, ` says Dr Barnes, `the decision to take steroids for an MS relapse will be based on personal experience and preference incorporating the views of the patient and physician.`

Surveys of UK neurologists also show variation about which type of steroid  to prescribe and in what dose. 

Below are listed the most popular regimens for intravenous and oral steroids used by neurologists for treating severe relapses, but different perspectives built up from experience over many years.

OR

While these are the most common regimens, other regimens are used which are equally reasonable.

Steroids treatment suppresses the body`s own steroid production. Suddenly withdrawing treatment  of steroids can be dangerous  so treatment lasting more than a few weeks is always phased out gradually to give the body’s glands time  to resume normal production of steroids used in MS are not long enough to cause concern about withdrawl.

STEROID SIDE EFFECTS

All drugs have unwanted effects. Because the course of MS generally extends over decades, both the short – and long-term side effects of drugs  are important. During an infusion of steroids, some people experience a metallic taste in the month. Occasionally, if the needle has been inserted incorrectly, the injection site swells and becomes painful. Increased heart rate, hot flushes or a red face may also occur. There can also be problems sleeping and an increased need to urinate, particularly at night.

Taking steroids can also affect people`s mood. Some people can experience a sense of euphoria that causes them to think there is an actual improvement in their MS. In contrast, one MS Matters reader describes her oral steroids as  `my angry pills`. For a small number of people, the highs and lows of mood swings can be severe enough to require additional medication, such as lithium or carbamazepine (Tegretol).

There is also concern over prescribing steroids because of fears about storing up problems for the future. Long-term side effects of steroids ought not to be an issue unless the patient is taking steroids excessively. The long-term side effects include:

USE IN OTHER TYPES OF MS?

Most neurologists do not give steroids in types of MS other than relapsing-remitting unless  there is a superimposed relapse of sufficient severity to justify their use. Having said that, many clinicians feel that no patient with MS who has progressive neurological disability should be allowed to worsen without being given a course of steroids at  least once. Occasionally, the response is worthwhile and the risk minimal.

WHAT ABOUT THE FUTURE?

New drugs like beta interferon are disease-modifying drugs. They can affect the natural history of MS. Steroids don`t  modify MS but they do speed recovery from relapses. Patients on beta interferon, for example, will be prescribed steroids as appropriate to help manage relapses.

Without doubt, steroids  will remain a useful weapon in the fight against MS. Much research is still needed to work out the best ways to administer steroids. Large and well-designed trials to look at many of the issues discussed here are long overdue.