Multiple Sclerosis: One Disease, Many Causes?

In one of our recent Facebook Live Q&A sessions, I was asked what I thought the biggest hurdle was that needed to be overcome in multiple sclerosis research.  Whilst funding problems are something that we have discussed at length, this article is going to be about something different – in particular, differences.

“No two people experience multiple sclerosis in the same way!”….how many times have you heard that phrase?  Whilst it may not be 100% accurate, it reflects the fact that we know MS is a very complex and complicated disease.  It can present in many different ways that result in many different outcomes in lots of different people.  In the science world, we say that it is a heterogeneous disease, meaning “diverse in character or content”.  For people, this leads to a lot of uncertainty after diagnosis about what their life will be like and what treatments are best suited to them.

But does this also impact on research into multiple sclerosis?

The answer is most definitely yes and probably for a couple of reasons.  One has to do with ‘time snapshots’, but I will deal with that in another article.  For now, I want to focus on the idea that has floated around for a while about the possibility that multiple sclerosis is one disease with many different causes.  Some may argue that, if this is the case, then MS is actually an ‘umbrella’ term for a number of different diseases that all look the same. However, for simplicity, I prefer the first description.

Let’s think about a research project trying to identify the cause of multiple sclerosis.  In the first example, we will assume that there is a single cause….just like a flu being caused by a virus.

The diagram below illustrates the hypothetical study that we have done – 10 people with MS and 10 healthy controls.  We have looked to see whether being born in April is the cause…those born in April are shown in red.

We can see that 2 people in the MS group were born in April, whereas none of the healthy control group were.   However, 2 out of 10 isn’t very convincing and if a single cause does exist, then we have no way of explaining how the other 8 have multiple sclerosis.  In this situation, we would conclude that being born in April does not cause MS.

Now let’s change our mindset when thinking about multiple sclerosis to that other idea – one disease, multiple causes.  Here we run the same experiment again, except we now look at being born in April (red), eating brussel sprouts (green) and living along a coastline (purple):

So firstly, let’s summarise the results:

Born in April:  2 in MS group, 0 in healthy controls

Eats brussel sprouts:  3 in MS group, 3 in healthy controls

Lives along a coastline:  1 in MS group, 0 in healthy controls

So what does this mean?  Well the fact that the numbers are the same in both groups suggests that eating brussel sprouts isn’t a cause of multiple sclerosis.  However, the other two conditions are found only in people in the MS group…though both in small numbers.  In our first hypothesis (e.g. one cause), we would have ruled both of these out as being causes of MS.

This conclusion changes slightly when we are open to the possibility of more than one cause.  Although only 2 people were born in April, maybe that is the cause for them and the other 8 have different causes.

Why is this a hurdle?  Well, you may have already realised the issue…if that second situation is true, our standard way of analysing these experiments will not work.

It’s important to say we don’t know which of these situations is true, but I think we have to at least remain open to the second possibility to ensure we don’t rule out potential correct answers.  It is just one of the many difficulties of researching such a complex, complicated and varying disease.  Fortunately, many dedicated and talented people continue to work tirelessly to find those answers as quickly as possible.

Lastly, don’t be worried if you are born in April, eat brussel sprouts or live along a coastline…those causes are fictitious, used purely for the purposes of my examples.  For further reassurance, just think, who in their right mind eats brussel sprouts!