What are the most common comorbidities that are seen with MS? Which ones are most likely to be managed or could be managed by a neurologist and which ones might require referral?

Dr. Marrie: It is important to be clear about what we mean by the term “comorbidity.” When I use that term, I’m referring to the burden of illness other than the disease of interest. So in this case, our disease of interest is MS, and the other conditions would be things like hypertension, diabetes, hyperlipidemia, depression, as opposed to complications that directly arise from MS, which might be neurogenic bladder, for example.

In terms of what’s most common, I usually broadly classify things into mental or psychiatric comorbidities and physical comorbidities. Psychiatric comorbidity is our most common comorbidity in the MS population at all ages. In particular, depression and anxiety. Depression will affect as many as 50 percent of the MS population over the course of their disease, and anxiety, if we consider all forms—phobias, panic attacks, generalized anxiety disorder and so on—probably affects 35 percent of individuals with MS over the course of their disease. So by far it’s the most common, and clearly something that neurologists managing patients with MS should be aware of. Psychiatric comorbidities adversely affect pain, fatigue and quality of life, and so the neurologist plays an important role in diagnosing and in some cases, treating them or working with the patient’s other providers to ensure that they are well-managed.

The most common physical comorbidities are going to vary a bit by age. The more common ones are things like hypertension, hyperlipidemia, which get more common with age. Migraine is fairly common, particularly in the young women with MS, as is common in the general population. Chronic lung disease is also common but is more likely to be asthma in younger individuals and chronic obstructive pulmonary disease in older individuals.

Comorbidities that affect at least 10 percent of the MS population also include irritable bowel syndrome, and autoimmune thyroid disease. With older age, cataracts, glaucoma, diabetes will become more common as well. Heart disease affects at least five to six percent of the MS population as they get older.

Some of these comorbidities, like migraine, are appropriately managed by the neurologist. Other comorbidities may not be managed by the neurologist, but he or she needs to be aware of whether these comorbidities may represent contraindications to some of the new disease-modifying therapies, or even be a consequence of those therapies. The neurologist needs to remain alert to these issues.

Given these psychiatric and physical comorbidities, what then is the neurologist’s role in trying to uncover these and the extent of them? Is it a simple matter of asking patients or are there specific diagnostic tests and things that neurologists should be thinking about doing for some of their patients that may not be considered routine at the moment?

Dr. Marrie: In terms of screening for depression, we know in the MS population that depression is under-diagnosed and under-treated, and there have been several studies that have evaluated screening tools that would allow a neurologist to rapidly identify the patient who needs further evaluation for possible mental health issues.

David Mohr, for example, looked at a two-item screen for depression where you can ask the patient, “During the past two weeks have you often been bothered by feeling down, depressed, or hopeless?” The second question would be, “During the past two weeks have you often been bothered by little interest or pleasure in doing things?”

If you get a “yes” to either of those, that is highly sensitive, around 99 percent, for major depression and the positive predictive value is 72 percent. So if you got a yes to either of those, you would then want to ask follow-up questions and determine whether further mental health assessment or treatment was needed.

Given the frequency of psychiatric comorbidity the neurologist should ask about mood-related concerns in all routine visits. Then, depending upon the severity of the symptoms and other characteristics of the patient and the history of the patient, you may opt to refer somebody for counseling and further assessment if you have those resources within your clinic or within your health system. Some neurologists may feel comfortable going ahead and treating with pharmacotherapy if that’s needed, or they may involve the family physician. But I do think that we have, because of the substantial burden of the psychiatric comorbidities, in particular, a responsibility to make that part of our care in terms of identifying that. I think that’s particularly important, given that I think that other providers don’t always realize how high that burden is in our patient population.

With respect to physical comorbidities, I think it’s reasonable for neurologists to check blood pressures when people come in for routine clinical follow-up, particularly now that some of newer disease-modifying therapies may increase the risk of hypertension. We also need make the other providers involved in the patient’s care are aware of the potential risks of comorbidity, whether drug-induced or not so that they can be addressed appropriately.

Presently we lack an evidence base to tell neurologists whether we need to treat physical and psychiatric comorbidities any differently in the MS population and the general population, but the first place to start is actually being sure that we know they exist.

Can neurologists make any assumptions about who is at risk for psychiatric comorbidities?

Dr. Marrie: I try not to make any assumptions about it. We know that there are multiple risk factors for mood disturbance in MS, including socioeconomic status and other psychosocial factors as well as factors related to MS disease activity. People can be depressed early in the disease, when they’re otherwise relatively well. You really can’t tell just by looking at somebody.

A two-question screen takes you a couple of minutes. So I think that given how easy it is to potentially identify the issue, that it’s a reasonable expectation to ask at every visit. Multiple studies indicate that these disorders are under-diagnosed in individuals with MS. Untreated depression can be associated with increased pain and fatigue and reduced quality of life. This warrants a systematic approach to evaluating every patient.

Are there any nonpharmacologic interventions that you think can be helpful to a patient, in general, and that you do tend to recommend?

Dr. Marrie: For several of the physical comorbidities that we’re talking about, common nonpharmacologic recommendations relate to eating a healthy diet, getting adequate exercise, getting adequate sleep and learning stress management techniques. These are things that can be applied broadly. When we realize our patients have been diagnosed with hypertension or hyperlipidemia or diabetes, it is a good time to ensure that they’ve been educated about their diet.

I think these lifestyle behaviors are important once people are diagnosed with the comorbidities, but they should also be encouraged shortly after diagnosis in the hope of preventing some comorbidities.

Is there any consensus building underway? What should clinicians do in the meantime?

Dr. Marrie: We do not have any consensus guidelines regarding physical comorbidities in MS although there are some recommendations for psychiatric comorbidities. Until recently the issue of physical comorbidities in MS has not been the subject of much attention, and we have quite limited knowledge about their impact on outcomes of MS. We lack the evidence base to make MS-specific recommendations about managing physical comorbidities.

At this point, we need to ensure patients are being evaluated in collaboration with the rest of their health care team according to general guidelines for the general population. Given some of the emerging literature suggesting things like the vascular comorbidities, hypertension, hyperlipidemia, heart disease, and their potential impacts on outcomes like disability progression, that we are moving toward a time where we actually should be explicitly evaluating whether we need different targets in terms of how tightly blood pressure and cholesterol should be controlled in the MS population. That’s going to require formal intervention studies to really give us good guidelines.

As we introduce more disease modifying therapies where some comorbidities are potential adverse effects, this topic will become increasingly urgent to address.

Dr. Marrie is Associate Professor, Department of Internal Medicine (Neurology) and Associate Professor, Department of Community Health Sciences at University of Manitoba. She is Director of the Multiple Sclerosis Clinic.