Philosophy of Care for the MS Patient

My name is Tracy Eicher. I am going to spend the next 20 or 30 minutes discussing multiple sclerosis and some of the concepts that we use to take care of multiple sclerosis patients in the year 2017. We’ll go over the basics of MS, including how the immune system affects the brain and spinal cord. We’ll discuss demyelinization, but, beyond this, what multiple sclerosis does to the grey matter of the brain. We’ll discuss models of disease, and the different perspectives that have changed over the years in how we view multiple sclerosis. We’re going to review advances in disease modification and the therapies that have changed over the years, as well as how we use the therapies. We’ll discuss vitamin D and its importance in keeping disease under control. We’ll also discuss shifts in how we view MS care and how we take care of MS patients today.

Multiple sclerosis comes from the immune system. It is not a disease that starts in the brain or spinal cord. The problem is actually in the immune system itself. The immune system is a very complex system made of cells and fluids and other chemicals that helps your body rid itself of things that should not be there. The immune system is made to identify what is foreign and attack it and get rid of it. The immune system needs to be strong and healthy in order for us to combat viruses, bacteria, and other things that should not be in our body. But when the immune system begins to attack the brain or the spinal cord or the optic nerve, it is called multiple sclerosis.

In order for the immune system to attack the brain or spinal cord, it has to cross the blood brain barrier. It’s a very complex process, and there’s a lot that we still today don’t understand. But we’ve developed a lot more understanding in the last five to ten years than we ever had. As we’ve developed more understanding of the immune system, our approach to therapies have advanced and expanded. All of our medications to combat multiple sclerosis take different approaches to balancing the immune system. We used to focus on the immune system’s attack of white matter. The white matter of the brain and spinal cord is called myelin, and we used to discuss this as a demyelinating disease.

But beyond this, it also attacks the nerve body itself, and that’s the grey matter. So grey matter has very much become a focus in MS as well. MS symptoms are varied and are different in every patient. This is because the immune system can attack anywhere in the brain or spinal cord, and it can attack the optic nerve. So symptoms could include vision loss out of one eye. It could include dizziness, balance problems, difficulty swallowing. Could be cognitive or it could be motor difficulties or sensory changes. There could be bowel and bladder changes and sexual dysfunction. All of these things are very common in MS patients, but not any one MS patient is going to experience all of these symptoms. And every MS patient will have their own unique set of symptoms and patterns based on where their immune system has attacked.

We sometimes say that every patient’s MS is like a thumbprint in that it’s unique and different, and their pattern of attack is very different. So it is very difficult for us to tell one patient what they will experience over the following five years or ten years. It’s very difficult for us to discuss with them what they will experience as a relapse, and sometimes we have to give them general ideas. And very often the patient just has to call if they feel like they may be having an MS relapse, and they aren’t sure. We used to discuss pattern of MS disease, and we still do focus on this to some extent. But as we’ve developed treatments for MS, I think our discussions have shifted away a little bit from just patterns to focusing more on what we can do about MS.

In the first picture on the left upper corner, this is relapsing-remitting MS. And this pattern depicts a patient who has an attack, and then it quiets down. And then later they have another attack which quiets down. Over time, they often have attacks which do not fully resolve and don’t full go back to baseline. And over time, you can see that stepping up, and that signifies advancing disability. On the right side, upper corner, you see primary-progressive MS. Primary-progressive MS is probably a unique type of disease, and it probably is separate from the other presentations of MS. But these are patients who never really have a noticeable flare or attack. They just very gradually get worse, and they very gradually feel like they’re losing abilities.

Primary-progressive MS is a very difficult disease state to treat. And, in fact, we don’t have any disease-modifying agents today that are approved for primary-progressive MS, although we have one therapy that is under FDA scrutiny right now. In the bottom of the slide, you can see on the left, secondary-progressive MS and progressive-relapsing MS. This is somewhat of a grey zone and identifying which of these patterns is exactly happening with the patient is somewhat of an art form, and sometimes we take our best guess. The important thing, I think, is that all patients who come into the disease with a relapsing-type picture are good candidates for our disease-modifying therapies.

When there are attacks, we know there is an inflammatory component, and our MS medications have shown to do well against the inflammatory part of the disease. Many patients over the years, whether it’s with continued events of relapse in between or a quieting down of relapses, do then begin to progressively worsen. And you can see that in both of these pictures on the bottom of the screen that over time there is a worsening of the disease and then increase in disability. This slide puts a lot of the ideas together into one picture, and this is the most common presentation of the disease. So on the left-hand side of the screen, the patient comes into the disease with relapses, and the relapses quiet down but maybe not going all the way back to baseline.

Over time, not all the relapses recover, and as relapses continue to occur, more disability is obtained. However, at some point in the disease, it’s very common that the relapses quiet down, and there is not so much of an inflammatory picture in the disease and just disability progression starts to prevail. During the time when there is a lot of inflammation, this is when we see the new lesions which I will show later in this slide show, and lesions are the inflammatory attack on white matter. There is also, to an extent, inflammatory attack at the grey matter, though it is more difficult to appreciate on MRI.

But beyond the inflammatory attack and subtlety underneath the inflammatory attack even early in the disease, there is attack at the grey matter. The nerve cell itself is being damaged, and that correlates more strongly with the neurodegeneration or the disability progression over time than even the accumulation of the white matter lesions. We’ve mentioned that we used to focus a lot on the demyelinating part of this disease, and I’d like to also focus on what happens beyond the white matter attack. In this picture, you can see what we call lesions in MS. The lesions are these white globs on the MRIs that you see.

Historically, this was the focus of what we looked at when we treated patients for MS. We talked to them about their lesions. We counted their lesions, and we thought that lesion load was the answer to why disability accumulated. But we realized, even years ago, that there were patients who had fairly extensive disability without extensive white matter lesions and that the lesion load doesn’t always correlate with how much disability there is. This is a picture of the brain that lets us take a look at where the grey matter is and where the white matter is.

The ribbon around the outer edge of the brain is grey matter. There are grey matter pockets deep in the brain, and those are pictured here, labeled basal ganglia. There are other structures deep in the brain that are pockets of grey matter or nerve cell bodies. On the right of the picture, you can see in the spinal cord, the center of the spinal cord, sort of shaped like a butterfly, is the grey matter. And around the outer edges, actually white matter. This is a better picture of the grey and white matter, and this is a picture of atrophy that occurs in MS.

On the right of the screen is a patient without atrophy. You can see that the area in the center of the brain is fairly small. The dark area, which we call the ventricle, is not very big. On the left, if you look at the ventricle in the middle, there is a large area of darkness. That is because atrophy has occurred, and as the brain grey matter shrinks, space is increased. This is another picture of the same thing. The patient on the left having less atrophy, and the patient on the right having more atrophy. In addition to just the increase in the ventricle size, it is a little more subtle, but you might appreciate that the space around the outside edges of the brain is also expanded.

And as we see more atrophy or shrinkage of the brain, we tend to see disability progression in our MS patients. This is a picture of one of the scales that we sometimes use to measure or discuss how much disability there is. This is called the EDSS scale. It’s often used in clinical trials to give numbers to describe how disabled the patient is. We use it a little less often in the clinic.

I’m going to shift focus now and discuss advances in disease modification. Our first MS drug came out in 1993, and it was an injection. Over the next several years, we developed other medications that affect the immune system in ways that improve the outcome of multiple sclerosis. But all of our medications in the early days were injections. At this point, we have developed more therapies, and we have IV therapies as well as oral therapies available. We still use the injections, but the pills have become a good tool for treatment. Patients like the ease of taking pills, and our IV therapies have become a very important tool in controlling multiple sclerosis.

A lot of our IV therapies are considered to be stronger. Often with strength also comes some increased risk. And so when we choose a disease-modifying therapy for a patient, we have to take many factors into account, including risks, tolerability, and how advanced their disease is or how aggressive their disease seems to be. It’s important to understand that all of our medications approach the immune system from a different way, and it’s not as if we were able to put our injectable therapy into a pill and you could take the same medication by shot or pill. These are different medications, and they do different things to the immune system to keep it balanced or controlled. Making the decision as to what disease-modifying therapy we start a patient on takes a review of that patient’s other medical conditions, their other medications, and also their lifestyle, as well as their MRIs and how their disease appears.

This slide is depicting the changes that occur in the immune system cells as they mature. As the cells mature, they develop different receptors, and our newer advances in MS medications are targeting many of these receptors in order to affect the immune cells different ways. In addition to developing better understanding of how we can affect the immune system through medications, we’ve also developed a greater understanding of how vitamin D can impact the immune system. Vitamin D has multiple effects on the immune system that are beneficial. Higher levels of vitamin D result in better outcomes for MS patients, and there are many ways that the vitamin D is affecting the immune system in a favorable way.

We have also advanced our ability to monitor MS patients, though, for the most part, we still rely on MRIs. We are developing the ability to use higher power magnets. We’re developing new technologies with the current MRIs, including double inversion recovery, 3D FLAIR, diffusion tensor imaging, and other research protocols that someday will be more widely available and not just limited to research.

Double inversion recovery allows us to see the grey matter better and to appreciate MS attack at the grey matter. That’s what’s shown in this picture. These are areas that the grey matter is being affected by MS. When we look at a regular MRI, it’s very difficult to appreciate these areas of attack. Diffusion tensor imaging allows us to evaluate the white matter tracts. It is especially useful if we are unable to appreciate discrete lesions in the spinal cord. Sometimes we can see disruption of the white matter tracts on diffusion tensor imaging. Optical coherence tomography is another tool that has been used more in MS clinics recently. This allows us to look at the thickness of the retinal layer. The thickness of the retinal layer may decline as the grey matter layers of the brain decline, and this is a way that we can measure loss of grey matter without directly looking at the brain.

In addition to advancing our abilities in MS medications and imaging, there have been several changes in the approach to care in the MS community. MS specialists are trending towards more frequent MRI monitoring. We are less tolerant of disease activity on MRIs and changes of disability even subtle. We are more likely to consider changing medications. MS specialists are being more aggressive with surveillance of vitamin D and supplementation of vitamin D to help keep the patients controlled. We are using more nonpharmacologic approaches, such as optimization of the abilities that the patient has through physical therapy, occupational therapy, and cognitive therapy. We are treating symptoms of the disease more aggressively and focusing on optimizing the wellness of the patient.

Due to the complexity of taking care of MS patients at the level that has become expected today, many neurologists and primary care physicians are turning to MS centers, and the MS center approach has become more popular. MS centers strive to offer a full spectrum of care, including a neurology team that consists of neurologists, MS nurse navigators, and medical assistants that are well-versed as the MS drugs and insurance approval needs. Physical therapists and occupation therapists are often highly involved in an MS center. Cognitive therapists and neurocognitive specialists are involved in the MS patient care as well. Social works, nutrition, and wellness support, as well as education and support groups are important. And many MS centers are now offering research trials that allow patients to have access to therapies that are otherwise not available.

The MS center approach is being used more widely, although often not all of the above are located in one place. Many times, a specialized neurology team is developed within a neurologist office, and then the therapies are sent out to other locations. However, it is important to develop a strong network with social workers, physical therapists, occupational therapists, and nutritional and wellness support, whether that is all in one location or through a network structure.

As we develop more understanding of MS and complexity of the disease grows, MS centers have become more and more important in being able to offer the level of care that MS patients need. Care of MS patients has advanced quickly over the last five to ten years and continues to advance. This is an exciting field for neurologists but a very difficult field for patients. Hopefully the podcast has been helpful in giving you an understanding of our current assessment of the disease and the disease state.