Tuesday, 26 September 2017

Should RIS (radiologically isolated syndrome) be treated?

Mult Scler. 2017 Sep 1:1352458517729462. doi: 10.1177/1352458517729462. [Epub ahead of print]

Radiologically isolated syndrome should be treated with disease-modifying therapy-Yes.

Okuda DT

Radiologically isolated syndrome should be treated with disease-modifying therapy – No

Andrés Labiano-Fontcuberta, Julián Benito-León First Published September 14, 2017

MS treatments are a caveat emptor. Global consumerism has hit the MS market succeeding in banishing moderation, thereby legitimising price hikes in the name of competition. It, therefore, falls to the responsible clinician to take the moral and ethical high ground. So, if science gives us the opportunity to treat early, regardless of cost, wouldn't it be wrong not to follow its instruction? Is, there an alternative viable option - realistically speaking? A transformative approach to early treatment in MS should therefore not be swept under the table. A pragmatic approach that demands an unequivocal demonstration of efficacy is not an approach to take in the path to a cure.

Okuda, above argues that MRI lesions in radiologically isolated syndromes (RISs) are very typical to those seen in MS in terms of appearance, frequency and distribution in the brain. Of those scanned 24% demonstrate contrast enhancing lesions on their baseline scan - it is well know that this cohort has further increased risk for future contrast enhancing lesions on subsequent head scans (Hazard ratio=3.4). Early DMT use, therefore, is a sound strategy for preventing further disease evolution.

"An estimated 11,000 axons are transected per cubic centimeter of contrast enhanced tissue".

Okuda, however, concludes with the realities of DMT use in MS: "Relating radiological features specific to in situ demyelination may be challenging at times. However, how truly accurate are clinical descriptions of experiences by patients that we routinely use to fulfill the clinical component of the diagnostic criteria in those with established MS? Would our concerns for treatment in RIS subjects be different if the costs of DMT were not so exorbitant or if the treatments provided were substantially safer than our current offerings?"

The counter argument for not treating RIS is provided by Labino-Fontcuberta and Benito-Leon. They argue on the point that the current risk-benefit ratio of DMTs is unfavorable for treating early. The current evidence is that ~ 7/10 RIS cases may not go onto develop MS in the next 5 years. In this case, a greater number would need to be treated to avoid developing MS, than is necessary. The authors appeal to a greater understanding of the nature of the disease at the RIS stage before we as a community offer treatments for it. 

"Emerging data suggest that in RIS, the clinical and pathological damage of magnetic resonance imaging (MRI) lesions might be compensated by more efficient reparative mechanisms".
I leave it to you to draw your own conclusions - are you for or against early treatment in RIS?


  1. Why would you have an MRI unless you were ill / were experiencing symptoms? Surely if there are signs of inflammation / damage to the CNS the patient should be treated. I think neuros have created problems by trying to dream up various was to describe the disease - RIS, CIS, RRMS, SPMS. As a patient, if I'm losing brain matter, I want it treated ASAP. Think of it like a fire in your house. If you saw that a piece of coal had fallen out of the grate and the curtain it had fallen by had just started smouldering, would you really do nothing? Why wait until the room is engulfed in flames before doing something! We have a major problem with the attitude of some neuros with the wait and see, softly softly approach. Time is brain but it's not their brain.

    1. The person may have had an MRI for another reason, such as head injury or lump in neck for example.
      The other problem is MS drugs could make other conditions worse. If the person does not actually have MS starting an MS DMT could create problems. There are several MS mimics on MRI.

    2. Yes, this is a good point - neurosarcoid for instance will not do well with the standard MS treatment. But this is why we do LP's and CT of the whole body when things don't quite fit. Recently, I had someone with white matter brain lesions and peripheral neuropathy, matched OCBs. CT demonstrated lymph nodes, and the person underwent fine needle aspirate which showed only reactive changes. The LN in the chest were not amenable to biopsy so they had CT guided biopsy of the abdominal LNs. The histology on this came back as lymphoma. A cautionary tale but the pathobiology of these two conditions exist on a spectrum (lymphoproliferative disorder versus autoimmunity)!

  2. Replies
    1. Check out my post on mincycline, the remark is in reference to this https://multiple-sclerosis-research.blogspot.com/2017/08/minocycline-as-neuroprotectant.html?m=1

  3. every time the question begins with the words "should" and ends with "we don't know"... i get the distinct feeling that the person in question (ie. the sufferer, the patient) should have the deciding vote. doctors, in this day and age, should make deicisions for those who ask for decisions to be made for them. the rest should have the right to make their own choices. the doctors' job, in those cases, should be to spell out the risk, in writing if necessary, but allow the dignity of autonomous decision making.

  4. Cochrane Database Syst Rev, 2017. Filippini et al, Treatment with disease-modifying drugs for people with a first clinical attack suggestive of MS.,
    (10 randomised trials, 8 open label extension studies and 4 cohort studies published 2010-2016);
    Conclusion. 'Very low-Quality evidence suggests a small and uncertain benefit with early treatment compared with placebo in reducing disability-worsening and relapses.'
    We need to understand the pathogenesis and cause of MS but alas the funding for this is not to the liking of the pharmacological companies. Early treatment, in the dark, of all patients who might go on to develop MS, is very much to their liking.
    As I have tried to point out on many occasions, in postmortem studies of the CNS of patients who never had any evidence of MS lesions throughout the course of their lives, have produced up to 20% positive for MS plaques. As GG has pointed out, the MS iceberg. Food for careful thought?

    Conclusion, (10 randomised trials

    1. I believe the MS society UK are sponsoring a moderately large study looking at early aggressive treatment. The point is a meta-analysis is only as good as the study number and effect size. Real life practice tells us that time is brain, similarly the case for argument for benign MS collapses under scrutiny, and then we are no further ahead than we were an year ago.
      This is not to say that advances have not been made, my experience is that the disabling MS which I used to see in clinic from the pre-DMT era are no longer seen to a large extent, and these drugs are clearly working. Of course, more research is always helpful but this should take place alongside drug development. The advances made in the management of MS are well beyond that of other neurodegenerative conditions, so I remain optimistic that if our colleagues had not taken the leap they did back in the 90s we would not be here now debating this.


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