Why does MS affect everyone differently?

Everyone experiences MS differently, for reasons which are hard to pin down. Why is it that the lower half of some people’s bodies are affected, for example, rather than the blurry vision experienced by others? Why would the immune system target different parts of different people’s brains?

What’s more, while some people see a resolution of their symptoms after just one flare up, more often, people develop an accumulation of disability after many relapses in what is known as progressive MS. 

The mechanisms which underpin these differing pathologies are the subject of extensive investigation, but to help us understand what we do know is happening in the body to bring on the difficult and varied symptoms experienced by those with MS, I’ve been speaking to Will Brown, a consultant neurologist at Cambridge University Hospitals who specialises in Multiple Sclerosis…

Will - So multiple sclerosis is the most common cause of disability in the young and in the UK there's more than 150,000 people with MS and for reasons we don't fully understand females are affected three times more commonly than males. At its heart MS is an autoimmune disease and what that means is that the immune system is misbehaving, it's attacking normal body tissues and in this case those are tissues in the brain the spinal cord and the nerve that goes from the brain to the eye called the optic nerve.

James - And particularly it's impacting the myelin sheath.

Will - Yeah and this is really interesting so we think that there's kind of two broad categories of things that can predispose to MS. So one of those is genes and the second one is environmental factors and we can come on to this but there's been recent work showing that one of the biggest environmental triggers is Epstein-Barr virus and actually this looks almost identical to one of the proteins that sits on myelin and so increasingly we're confident that this is an autoimmune disease. The immune system is making a mistake, it's trying to attack myelin thinking that it's Epstein-Barr virus and it's our job to try and get that back in check.

James - Now Epstein-Barr virus is something that the majority of the population will get infected with over the course of their life. This is the virus that can cause glandular fever I think I'm right in saying. So what is it that causes the people who go on to develop MS to experience the condition that they do?

Will - You're exactly right so over our lifetimes more than 90 percent of us will be infected with Epstein-Barr virus. By the age of 10 that's more than half of us and what we don't understand is why some people go on and develop MS. It seems that some of that risk is due to genetic factors but again those are not completely understood.

James - I'm really interested to go into a bit more detail and zoom in a bit more on the immune response and what's actually happening in a neuron-to-neuron context so talk me through the immune cells involved and how they come to be interacting in the brain in the first place.

Will - So in health we know that there are naughty immune cells and autoreactive cells and they are normally cleared up in the thymus. Some of them will escape into the periphery but they again will be mopped up but people with MS these mechanisms they seem to fail in particular there seems to be reduced levels of t-regulatory cells and there's also some of the effector cells t-cells and b-cells seem to be less responsive to these mechanisms and this means that these cells can then trigger t-cells and b-cells to cross the blood-brain barrier enter the brain spinal cord and optic nerves and then lead to the attacks that we see that cause relapses.

James - When these naughty t-cells as you describe them cross the blood-brain barrier, what's the focus of the disease, what's the damage done?

Will - This autoimmunity this wave of inflammation as the inflammation happens it leaks out from the blood vessels into the surrounding brain and we can see that on a brain scan we can see these new areas which we call lesions in the deep tissue called the white matter and as the inflammation leaks out it causes the insulation that surrounds the nerves to come off and hence we call it a demyelinating condition because that protein is called myelin. And that means the nerves don't function so well and as a result people experience symptoms that may be weakness or numbness imbalance problems and problems with their eyes for example but over time the inflammation will improve and the myelin will go back on the body can repair itself and that leads to an improvement in symptoms and so after that episode which we term a relapse there's a period of relative stability and during that time there'll be no new symptoms until the next wave happens.

James - Is treating MS just a case of treating the inflammation and the flare-ups as they occur and relapsing remitting manifestations of the disease?

Will - So sadly not. Increasingly we're realising that inflammation is the biggest component at the beginning of the disease but we're also realising that other processes are happening right from the beginning. These are processes that lead to nerve death and these ultimately lead to the most disability.

James - For relapses, symptomatic periods of the disease, how effective are the treatments?

Will - So I'm a little biased but I'd argue that multiple sclerosis is one of the most exciting areas for therapeutics and that's because it's one of the few areas of neurology where we have truly disease modifying treatments. So since the late 90s more than 20 treatments have been licensed which can effectively reduce relapses and the disability that comes with them. I classify these into low, moderate and high efficacy all on the basis of the impact on relapses. So low efficacy treatments , which were the earliest ones that came about, reduce relapses by about a third and similarly they have a reduction in disability that comes with each relapse. More recently tablets have been licensed. These reduce relapses by about half. And finally the high efficacy treatments reduce relapses by about 80 to 85 percent and with a correspondingly greater effect on disability. But it's not that simple. With increasing efficacy usually comes increasing risk and also the monitoring requirements. So the decision is not simply a case of what's the strongest treatment we can give someone but it has to be a joint decision made with the patient to figure out what is the right treatment for them, what treatment do they need in terms of efficacy but also choosing based on their safety profiles, their family plans and also monitoring.