Symptom Management in MS

Fred D. Lublin, MD: One of the areas of MS [multiple sclerosis] that my colleague, Stephen Krieger, MD, always reminds me about is symptomatic therapy. His mantra is: There’s always something you can do—from the patient who comes in with very early disease, to the individuals that Tom is referring to that sort of drop off our radar screens because they’re so badly involved, and everything in between. So we’ve been very excited now for 25 years, almost 26 years over disease-modifying therapies. But symptomatic therapies are what make people’s lives better. And while we don’t have time to go through a whole list of them, there are things out there that we ought to make sure that the general public is aware of.

James M. Stankiewicz, MD: I think there are a number of different things that we try. I mean the thing that most readily comes to mind is dalfampridine, which is a drug that’s indicated for walking dysfunction in multiple sclerosis. It was approved based on the strength of 2 pivotal trials showing 30% of patients responding with 20% improvement in walking times. In clinical practice, I find that it’s actually more frequent. Patients respond probably about 50%. I don’t know how much of that is placebo effect versus a real effect, but either way I’m happy when patients have this response.

And in practice, what I find is that patients say not so much that they can walk faster but they can walk further before they get tired, or they feel like they’re a little stronger in the legs. And so, that’s something that certainly I think makes sense to try. I don’t think there’s a lot of downside, and the patients will know pretty quickly whether they’re going to have a response. It can be discontinued if they don’t really notice much difference.

Another thing that we sometimes try for patients with urinary dysfunction, dyssynergia, spastic bladder—Botox can be useful. Another option is a combination of dextromethorphan and quinidine for pseudobulbar dysfunction. It’s something to keep on the radar because it’s something we can do something about. In practice, I don’t think it comes up that frequently, but I always worry that I’m not asking as much about it as I should. I try to be vigilant.

These are the more recently approved things, but we have medicines that go back for many years like baclofen and others that can be helpful. We use modafinil or armodafinil for fatigue in some patients, or amantadine. I sometimes find that amphetamine salts, in the right context, can be helpful for patients with cognitive dysfunction or fatigue. You have to be careful of [adverse] effects, but in the right patient sometimes I think it can be appropriate to try.

Fred D. Lublin, MD: Other thoughts on symptomatic therapies?

Patricia K. Coyle, MD: I just throw out posterior tibial nerve stimulation for neurogenic bladder. I’ve had some patients who have had very good results with that.

Thomas P. Leist, MD, PhD: I think it’s also very important to keep in mind that many of our patients with multiple sclerosis do have depression. Neuropathic pain is a significant issue in patients, and perhaps just to give a shout out to the fact that in multiple sclerosis pain is normally best controlled with antiepileptics or antidepressants and not with narcotic pain medications.

Fred D. Lublin, MD: Good point. Symptom therapy is really very different strategically from what we’re doing with disease-modifying therapies, where we sort of prescribe it and then we sit back and wait. Symptom therapy has the advantage that you know, as you alluded to, pretty rapidly whether you’re doing any good or not—whether it be dalfampridine for walking, or baclofen, or one of the other anti-spasticity agents. But then the onus is on the clinician. You’ve got to keep actively working with the patient for dosing. While we don’t use dosing for the disease-modifying therapies, we do it for things like bladder control—not for dalfampridine, that’s a standard dose—certainly for spasticity, and maybe even for depression. So that requires a lot of back and forth and interaction with the patients, and constantly working with them over a short period to optimize what they’re doing. But, there again, you know it’s going to work or not work pretty rapidly.

Suhayl S. Dhib-Jalbut, MD: I think another thing to remember about symptomatic therapy is cognitive dysfunction, which is extremely common. I mean, 40% to 60% perhaps of patients have cognitive difficulties. We now know that perhaps cortical lesions are important. They correlate with cognitive problems. The question is, what are the factors that contribute to cortical lesions, and is the pathogenesis of cortical lesions different from the variety of lesions in MS? And how can we target or prevent those lesions?