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Hello, and welcome to Episode Twenty-four of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.
This week’s podcast features an interview with Professor Aksel Siva about asymptomatic MS. But to begin, here’s a brief summary of some of the latest developments on the MS Discovery Forum at msdiscovery.org.
We just uploaded a new data visualization to our website. This one breaks down the design of MRI-related clinical trials in MS. It combines 88 trials conducted between 1998 and 2013 in a colorful, interactive dot plot. Each dot represents a point in time for a particular measurement, such as brain volume. You can sort trials by phase, and you can look at trials in aggregate or one at a time. To view this new visualization, go to the Data Viz section under the “Research Resources” tab and click on the top link.
Magnetic resonance imaging is a source of anxiety for many people with MS. Just getting into the machine is nerve-wracking, and waiting for the results is even scarier, says a recent study from PLOS One. The researchers conducting the study suggested that educating patients about MRIs might alleviate some of the dread. Even though MSer’s typically know a great deal about MRIs, understanding how to interpret their own results may help increase the bond of trust with their physicians, the researchers said. To read more about the study, visit our “News and Future Directions” section, and under “News Briefs” click on the article, “MRI Education May Benefit MSers.”
Have a burning question? A bone to pick? Something you want to get off your chest? Start a discussion! We invite you to participate in our discussion forums by making your own threads and commenting on others. Just click on the “Discussions” option under the “Forums” tab on our website to get started.
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Now to the interview. Last week, we spoke with Professor Aksel Siva about radiologically isolated syndrome. This week he’ll be speaking to us about asymptomatic MS and approaches to medicine in Turkey.
Interviewer – Dan Keller
Professor Siva, first of all, why is it MS if it’s asymptomatic?
Interviewee – Aksel Siva
Well, that’s a very good question and very difficult. But now with the tools that we have in medicine, we probably diagnose people without developing the disease. And, again, if we look to some other neurological diseases, today we are now discussing whether we can really diagnose Alzheimer prior that the individual develop the disease with imaging, with biomarkers, and so on. So to see the same thing in MS, I think it’s not really something very different. The thing is that not all these people will develop the disease, so the way we have been trained as clinicians, to us it’s important to see clinical signs and symptoms.
But now we have to start seeing that not everybody will develop the disease even if they do have it biologically, morphologically, or whatever you name it, however you name it. And then when they develop, we know well that all people are not going to have the same course. So these individual differences based on genetic background, maybe environmental influence, or whatever, should put a light in the way we see individuals – not a disease, but the individual with the disease rather let’s to say than the disease affecting the individuals. So I think this concept of subclinical disease, which is not only for MS, should influence our practice or our approach to our patients, and also in understanding the diseases and how to manage them.
MSDF
Can you tell me a little bit about some of the studies that show heightened susceptibility and that possibly invoke the idea of genetics or environment?
Professor Siva
I don’t think that I am in a state of responding to this question, because this is not really my area of interest. But from the genetic studies, we know there are some people who have the susceptibility genes, some who have the protective genes, and also some genes that may probably affect the course and prognosis of the patients. But, again, to my knowledge, what we have today, the information we have, is not really unique for everybody. It’s also very heterogeneous. So we need more time, and I think that this time it’s not too far, and especially the Genetic Consortium in the US, their findings are going to bring a lot of new information in the very near future.
MSDF
What about studies on twins or just siblings. Although it doesn’t really nail down whether it’s genetic or environmental, it does speak to heightened risk. What did those show? Who looked at them and what did they find?
Professor Siva
Well, again, I’m not aware of really very new studies on twins; identical and non-identical twins, the risk is very different, it’s maybe 2 to 3% up to 5%, depending like if it’s Canada or France it changes. But when it is identical, it’s 25 to 30. To my knowledge, the Canada cohort went up to 37%, although this number, I guess, was not published, but we know this. So it’s about only one-third even in the highest identical twin studies. So the question is what happens to the two-thirds? Maybe some of them do have incidental lesions, but they don’t have the disease. What is the present state in this genetics or others, I’m not aware of.
MSDF
Even siblings who show oligoclonal bands don’t necessarily have or get the disease, is that correct?
Professor Siva
No, that’s correct. According to the Swedish study, these people did not have the disease. Maybe more important, there was a subsequent paper reported in the same cohort, they have looked in the CSF of these asymptomatic, or let’s say of these siblings with positive oligoclonal bands, and what they called immunopathic trait. They looked in some other issues, but let’s put it these people with positive oligoclonal bands and the immunopathic trait, and they have looked in some neuronal degeneration markers. And the sibling who had the disease had high levels, which shows that there was a CNS damage, and asymptomatic case it was normal. So that is very clear that, yes, if you get the disease you might have some, let’s say, the biological evidence of it together with CNS damage, whereas if you don’t get… you may have the same trait but not the disease, because you will not have CNS damage. And there might be some underlying mechanisms – immunogenetic, whatever – which controls the disease spread and clinical expression. So I think this is a major issue.
And in the Steffano study when he had studied, again, the relatives of people with MS who had lesions – these 4% or 10% of asymptomatic cases – he also looked in the normal-appearing white matter. And in the diseased individuals it was abnormal; whereas in the people who had just those, let’s say, T2 changes, the normal-appearing white matter was completely normal, which again shows us that the CNS damage is very, very limited in people who don’t get the disease. And from the early autopsy studies, again the people in whom the autopsy had shown brain lesions, they were mostly periventricular and probably in silent areas, and there was not widespread damage as we see in people who get the clinical disease.
MSDF
It seems Turkey is a very good setting for looking at a lot of this, because people get a lot of MRIs.
Professor Siva
That’s correct, that’s very correct, and that’s why we have so many cases. Today with contribution of another medical school from Ankara, Hacettepe Medical School, together now we have more than 86 RIS cases that we continue to follow up, some of who have converted now.
MSDF
And RIS is radiological isolated syndrome. Do people pay for their MRIs, or why are they so apt to come in and get so many?
Professor Siva
Not really, it’s reimbursed, mostly it’s reimbursed, or if they have their private insurance because, let’s say, physician is suspecting something. And I should also confess that in some hospitals – mainly state hospitals – there is an overload of patients. Let’s say neurologists in those institutions may not find time to listen and examine the patient as they should do. So in order not to miss something, even a patient who comes with a headache may get an MRI.
MSDF
Is there a difference in Turkey of how you approach MS patients, or treat them, or follow them from in other countries that you’ve noticed?
Professor Siva
Not really. It’s, I would say, very much the same. I have started our MS clinic in 1987 here, and today we have more than 7,000 registered patients, which is really quite a very large population. This doesn’t mean that we follow all the 7,000 and more patients because many of them had been referred for second opinions, but I would say we continue to see at least half of these people. And the way the practice is here is not any different than most major European and US centers. I had spent some time at Mayo many years ago and I had some of my other colleagues now who had spent some time. So it’s more or less the same. We have all the same drugs, most of them are reimbursed. So we have many alternatives for our MS patients, although there are some restrictions for reimbursement. We need to at least try the so-called injectables in order to go to orals, or, let’s say, the monoclonal antibody therapies, but almost all are available. And according to some rules, they are also reimbursed.
MSDF
Are there good patient support services, psychosocial and other?
Professor Siva
Not maybe so strong. That we may differ a bit from Europe and US. We do have Turkish MS Society where such services are tried to be provided, but that is not enough. We do have some MS Society chapters in some cities but not everywhere. But mostly the problem, I would say, is economical. All these services mostly are based on voluntary basis.
MSDF
Do you think that patients react the same to their disease?
Professor Siva
We do have some studies – psychologically, physically – and it’s at very similar to western theories. So actually Turks are Caucasians mostly, and therefore it’s what if we are going to call the western-type MS, that’s what we see here too.
MSDF
Are there cultural differences in various parts of Turkey how people view their disease, or is it all about the same? I mean, Istanbul is really Europe, as you move farther east you get into more Asian and Middle Eastern.
Professor Siva
I may say not really, because we get referrals from all around Turkey, and the behavior is not really much different. I should say either whether the patient is from Istanbul or from the east part of the country or the Mediterranean, it’s more or less the same.
MSDF
Anything important to add that we’ve missed or interesting topic points?
Professor Siva
We have a large number of MS people in Turkey, probably prevalence rate is around 50 per 100,000 or more. There have been a number of prevalence studies, and this is about what we can really derive from all the studies – 50 or more even. But I have the impression that we are getting more and more MS in Turkey today, and more familial cases, which was not the case maybe 15 to 20 years ago.
MSDF
Very good. Thanks a lot.
Professor Siva
Thank you.
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Thank you for listening to Episode Twenty-four of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.
Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.
We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.
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