Multiple Sclerosis Discovery -- Episode 52 with Dr. David Tabby

[intro music]Host – Dan Keller Hello, and welcome to Episode Fifty-Two of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.This week’s podcast features Dr. David Tabby, who discusses the incidence of headache in MS. But first, here are some new items in the MS Discovery Forum.According to our curated list of the latest scientific articles related to MS, 53 such articles were published between August 14 and 21. To see these publications and the articles we selected as Editors Picks, go to msdiscovery.org and click on Papers. We’ve made some recent updates to our Funding Opportunities and our Meetings and Events listings, both of which can be found under our Professional Resources tab. Be sure to take a look at a newly-posted funding announcement entitled, “National MS Society: Health Care Delivery and Policy Research Contracts.” If you know of any meetings, events, or funding opportunities that are missing from our lists, please email us at [email protected] so that we can include them. Our Drug-Development Pipeline includes continually updated information on 44 investigational agents for MS. This past week, we’ve added one new trial and 15 other pieces of information. The drugs with important additions are dimethyl fumarate, fingolimod, glatiramer acetate, interferon beta-1a, interferon beta-1b, and ofatumumab. To find information on all 44 compounds, visit msdiscovery.org and click first on Research Resources and then on Drug-Development Pipeline. [transition music]And now to the interview. Dr. David Tabby is an adult general practice neurologist, with a subspecialty in multiple sclerosis, in Bala Cynwyd, Pennsylvania. He was formerly associated with Drexel University College of Medicine in Philadelphia where he carried out the study on headache and MS that we discussed.Interviewer – Dan Keller Could you just tell me what the aim was? I think you were looking the variables affecting headache occurrence in MS patients.Interviewee – David Tabby Well, to be perfectly frank about that, my business manager had noted that many of my MS patients also had migraine, and she asked what’s going on with that. So we did a cursory review and found that close to 50% of my MS patients also had migraine. So that prompted the survey in a more formal fashion.MSDFWhom did you look at, and what were some of the variables you looked at?Dr. TabbyWell, we looked at everyone who was willing to answer a survey. And we wanted to include some typical migraine variables like frequency and intensity and triggers and age of onset and duration at that time and which came first, MS or migraine.MSDFAnd what were some of the major findings?Dr. TabbyI think our biggest contribution was that it seemed that we could correlate exacerbations with increase in headache, which I don’t think was known before that. Sometimes headache a little bit before the exacerbation, and sometimes exacerbation first, then with headache. But that raised the question about the role of inflammation in both headache and MS exacerbations. You know, I don’t think one is the cause of the other, but they’re clearly related.MSDFWhat about migraine with aura or without? Are there differences in the MS presentations or symptoms or relations in time?Dr. TabbyWe didn’t have a lot of migraine with aura patients. That’s only about 20% of the migraine population anyway. We didn’t have a big enough number to make any kind of association that would be distinguishing migraine with or the migraine without aura.MSDFDo you have a proposed mechanism in mind how these two may be linked – mechanism of migraine, mechanism of MS?Dr. TabbyI don’t think there’s a lot of work about what the immune system’s role is in migraine, but stress affects the immune system. My patients tell me that a particularly stressful event can seem to precipitate an exacerbation, and, no big secret, that stress can precipitate a migraine.MSDFFatigue can be a trigger, and obviously, that’s a large proportion of MS patients have it. So do you think there may be a link there, one triggering the other?Dr. Tabby90% of MS patients will complain of fatigue at some point, and I think that’s clearly got something to do with it. So anyone with migraine will tell you that when they overdo it and get overtired, they get a migraine.Interviewer – Dan KellerI think I saw something in the paper was talking about metalloproteinases in the CNS and leakiness of vessels and allowing either antigens out or T cells in. Does that have any legs or where does that idea come from?Dr. TabbyThat idea came from a paper that we found in our literature review of the basic pathophysiology of an MS exacerbation that matrix metalloproteinases have to be activated first, to increase vascular permeability of the CNS. Migraine was thought, at one time, to be a primarily vascular issue. It’s not. It’s primarily a neurochemical issue that affects the vasculature, but results in dramatic changes in blood vessel permeability. There’s a kind of leakage of fluid around blood vessels, which helps make them more sensitive.MSDFThere’s also a component of calcium flux in migraine. Would that have any effect on the immune system? There’s calcineurin inhibitors that are immunosuppressants, so I’m wondering if calcium in itself – could be an imbalance be a stimulant?Dr. TabbyThe role of calcium in modulating neural function can’t be overstated. I’m not ready to give you an exact mechanism of how that might function.MSDFPatients with migraine supposedly have more symptomatic clinical course of MS. Do you have any numbers there? What did you find?Dr. TabbyWe weren’t a longitudinal study. We’re really just a snapshot kind of picture to determine, you know, a relationship now. That was another one of our hypotheses that the worse headache you had the worse MS you were going to have. Our take-home message from the paper was MS doctors should be very aggressive about addressing migraine symptoms in their patients, because we think that it could have an effect in long-term prognosis in MS. And it’s not just the patient complaining about, oh, I have a really bad headache. There is a relationship. It’s been known for many years. I mean, you might have seen in our bibliography that some of the papers went back to the 1960s about the relationship with headache and MS. So, just to reiterate, migraine prophylactic therapy, migraine abortive therapy is important in the context of treating MS.MSDFCan pre-existing migraine before the MS diagnosis give you any clue as to being a risk factor in itself?Dr. TabbyThat’s an excellent point. We didn’t have a big enough group to come to that conclusion, but 12% of Americans have migraine – 18% of women, 6% of men. Less than 1% of the population has MS. Something else has to be happening.MSDFAlso, I guess you found that people with stabbing pain had more acute MS exacerbations than if they had other more throbbing kinds of pain.Dr. TabbyWell, we were just using that as an indicator of severity of the headache. Stabbing’s not a typical word used to describe migraine. We gave choices. We just didn’t leave it open-ended. We gave some example words for their responses to the survey to tick off. Yes, stabbing was one of them, and there was a correlation between the ones who said stabbing and worse exacerbation.MSDFSome of the patients you surveyed did not have pre-existing migraine, only after their MS diagnosis. Do you think that migraine is something that one should investigate whether they actually may be in a prodrome of MS, if they present late - develop migraine late in life – later in life?Dr. TabbyIn our world, pretty much everyone with a bad headache who sees a doctor about it, at some point is going to get some sort of imaging study of the brain. It might be a CAT scan, in which case there might not be enough information. But if it’s an MRI, there’s a good chance of seeing high-signal lesions scattered through the white matter. They may be real small and not particularly typical of MS. But not uncommonly, they’ll see a pattern that looks really quite like MS. And you examine the patient, and you don’t find anything that’s consistent with MS. You do a history, and you don’t find any symptoms that are consistent with MS. So this is the sort of thing you just file away and see what happens. I don’t think anyone would suggest that treatment for MS should be started at that point. There’s an entity that’s finally gotten a name, called radiologically isolated syndrome, which people get MRIs of their brain for some reason – head trauma, headache, anything really – and the pattern looks really quite like MS, but there’s no clinical support of MS. So same thing; we don’t forget about these people. You recheck their MRIs at some point in the future. You look for new lesions or enhancing lesions. I think the latest statistic is somewhere around 50% of them are eventually going to present as having multiple sclerosis.MSDFWould each entity be treated or each condition be treated as if it existed in isolation? Or do they complicate the management of the other?Dr. TabbyMy approach has been to treat them independently. Just follow the basic principles of headache treatment for the headache and the basic principles for MS treatment and adjustments of therapy and symptomatic therapy for MS. I would not suggest some interlinked therapy system.MSDFBut something like interferon and possibly other drugs may cause exacerbation of headache. Would that lead to noncompliance of the MS treatment or would you switch drugs or how do you handle that?Dr. TabbyThat doesn’t necessarily involve the headache issue. I think someone who has bad headaches on interferon who’s not taking their medicine, you know, you might try to fix it – fix the headache that is. But you’re probably fighting an uphill battle when that patient has negative associations with taking their medicine. I still tend to think of these two things as related but separate.MSDFSo what’s the big take-home message for a physician?Dr. TabbyReally just about treating migraine aggressively in their MS patients, and keeping in mind that we work very hard to preserve function to reduce the accumulation of disability, with drugs and other sorts of interventions. But intervening for migraine may be just one other way to reduce the burden of disability in the future, for your patients.[transition music]MSDFThank you for listening to Episode Fifty-Two of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations. Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to [email protected]. [outro music]