Multiple sclerosis is a disabling central nervous system disease. MS may result in a range of physical and cognitive problems. Globally, 2.3 million people live with multiple sclerosis. There is no cure.
Recently a study at UVM identified misdiagnosis of MS as a problem with significant consequences for patients. Recent pilot studies at UVM also showed that new MRI methods may improve MS diagnosis.
Andrew Solomon, MD, is a neurologist and division chief of multiple sclerosis at the UVM Medical Center. He is also associate professor in the department of Neurological Sciences at the Larner College of Medicine at UVM. He was the lead researcher for both studies.
How common is Multiple Sclerosis?
Solomon: Multiple sclerosis is quite common. It’s a frequent cause of disability in young people. Usually, people are diagnosed around their teens, or 20s, or 30s, although people can be diagnosed at any age, including older patients as well as children. But, it often strikes people in their 20s and 30s. It’s more common as you get further from the equator, for a variety of reasons. It’s very frequent in Vermont, possibly as frequent as 1 in 400.
We’re not sure why exactly, but we’ve known for a long time that the further you get from the equator, north, and south, there’s a higher prevalence of MS. That has to do to some degree, with where you’re born. This risk stays with you. If you were born at a high latitude and moved to the equator, for instance, later in life, you would still have that higher risk of MS. There’s something about the environment. It may be something about infections in those regions. We also think that vitamin D plays a role, as well as low sunlight, in regions further from the equator. Those influence immune function in ways that may increase the risk of MS.
Now, those are not the only risk factors for MS. We’re studying a large number of risk factors that may influence people with a higher genetic susceptibility for this disease. There’s not probably one cause.
What are the signs and symptoms of MS?
Solomon: Since MS can involve any part of the central nervous system, there’s really a broad array of symptoms that people can present with for their first symptom of MS. People can have symptoms that involve vision, so they may have trouble with blurry vision in an eye or two eyes. They may have trouble walking. They may have trouble with new sensations that are uncomfortable, like, numbness, or burning, or tingling.
People can have trouble with dizziness. MS can involve bladder function, or thinking and concentration. It can be quite difficult to diagnose at times. The disease, the phenotype, we call it, the expression of the disease in terms of its clinical manifestations is very heterogenetic. People can have a lot of different versions of MS.
Some people can have a more aggressive version, and some people can have a mild version of MS. Some people have more, what we call, inflammatory aspects of the disease, while some people have more neurodegenerative aspects of the disease. In sum total, this means it can present in a broad variety of ways.
How do you diagnose MS?
Solomon: Presently, there is no one test of MS. There’s no screening test or blood test that we can do and say, “You have MS.” Essentially, people can present with a broad variety of neurologic symptoms. Diagnostic criteria have evolved over time, so we rely on neurologists, or MS specialists, in particular, to be the screening test.
We evaluate clinical symptoms that are classic for MS as well as MRI and the spinal fluid of these patients to see if they fit within these diagnostic criteria.
Are there a lot of different diseases that can mimic MS?
Solomon: Yes, there are many many diseases that can mimic MS, unfortunately. Some of them are inflammatory or autoimmune diseases. As we found in our research, common diseases like a migraine can mimic MS. Migraine can cause neurologic symptoms. It can cause of numbness, or tingling, or vision changes. It can also cause MRI abnormalities. MRI abnormalities — scarring of the brain — are associated with a migraine, and quite common. It takes somebody with expertise to be able to distinguish MS from a migraine.
Part of the problem is that our diagnostic criteria involves imaging. There’s a tendency, it seems to be, at this time in medicine, to rely too much on some of this imaging, or MRI tests at the expense of a good clinical examination, a neurologic examination, and a history. Particularly, if somebody has an abnormal brain MRI, which can be caused by any number of reasons. High blood pressure, migraine, and very common diseases can cause some scarring on the brain. We accumulate little areas of abnormalities or scarring every decade of our lives for a variety of reasons.
What are next steps for MS specialists, and other providers, and practitioners in the field?
Solomon: We need better education on the appropriate use of MS diagnostic criteria. Our diagnostic criteria was revised in 2017 and it has a number of caveats for each step on how to make a diagnosis of MS. This revision of the criteria, more than any other, has a lot more detail to guide physicians on how to use it appropriately. Close attention to its proper use, ideally, through educational efforts, is going to help us prevent misdiagnosis of MS and accurate diagnosis in patients with MS earlier and appropriately. That’s number one.
The second thing we need is the development of objective biomarkers for MS. Now, we haven’t had much luck over the last 20 to 30 years with this effort. But, we’re entering this era of “precision” medicine where we are getting data from patients, and their genetics and their immune markers, that we may be able to combine using things called machine learning, and in combination with novel MRI techniques we may be able to better develop objective tools that will help us say, yes or no, if somebody has MS.
The fewer clinical decisions or judgments that we have to make, the better. Developing tests that are automated to guide diagnosis is what we need. They don’t just leave it up to the discretion of a clinician to make a judgment or an assessment when they have a question.
What other research are you doing at the UVM Medical Center?
Solomon: The goal or the primary aim of my new NIH grant-funded research is to develop new methods and more sensitive and specific methods to diagnose MS.
We don’t have a screening tool for MS, so we’re looking for methods that will provide information on the likelihood of MS before a neurologist evaluates a patient. We will test five new MRI techniques. We’re taking MRI pictures that will give us information about the volumes of different parts of the brain that tend to be affected by MS. We’re looking at blood vessels and the relationship to scarring in the brain. It seems that most MS lesions, or areas where there are abnormalities in the brain, there’s a blood vessel in the middle of it where the inflammatory cells come out. We’re able to image that for the first time.
Additionally, we will look at myelin in the brain and the volume of the spinal cord. These changes happen very early in MS and not so much in other diseases that can look like MS. We hope to develop some sort of a threshold where we say, “This is abnormal.” Similarly, we’re going to look at some new blood tests that look at the expression of RNA, as well as other immune markers.
We will also use machine learning to see if we can predict MS better combining the results of these methods. The idea is to recruit a large cohort of patients that we’re seeing the University of Vermont MS Center over the course of several years. Anybody who comes in for a new visit for an evaluation of MS may participate in this study to help us develop these methods to better diagnose MS.