Bridging the phases of migraine
A migraine attack is usually divided into four distinct phases, plus the symptom-free interval between attacks. How do these phases go together? Searching for treatment beyond "motherhood and apple-pie" advice.
+++ UPDATE with two figures I'll present at the IHC2011 +++
While some of us are waiting for the Lindau Nobel Laureates meeting, I look forward to The 15th Congress of the International Headache Society (IHC2011) in Berlin. The IHC2011 takes place in the week before the Lindau meeting, from June 22-26. Maybe I'll meet a future Nobel Laureate there, the one who has found "the holy grail of migraine treatment", as Peter Goadsby, a migraine expert, recently called it.
Just last week, the 53rd Annual Scientific Meeting of the American Headache Society ended in Washington. This is an intense migraine meeting month, though I must admit, I skipped the US meeting. June is also National Migraine Awareness Month in the US.
Such meetings are also always the time of heightened and unfortunately also often confusing—to say the least—press coverage. This time, Melinda Beck, a health columnist at The Wall Street Journal, did a large and very accurate report including a movie and a podcast: "Beware, a Big Headache Is Coming". What I liked most was the image below. It would be worth being on the cover of The New Yorker, if you ask me—ok, I am a migraine researcher, so I am biased. Anyway it was in The Wall Street Journal.
Visual disturbances and light sensitivity are my research field and several blog posts are on this subject, furthermore, as readers of this blog know, I work on the mathematical prediction and analysis of functional-imaging data obtained during the aura phase. Here is what Melinda Beck wrote in The Wall Street Journal about this phase.
Functional-imaging studies of the brain have revealed another tantalizing clue: During the aura phase, a wave of electrical activity sweeps over the outer, furrowed layer of the brain known as the cortex, at a pace of 2 to 3 millimeters per minute. This wave—known as "cortical spreading depression"—activates nerve cells as it goes, and the symptoms sufferers report typically correspond to the area of the brain the wave is passing over. For example, the patient sees flashing lights and wavy lines when the wave is over the visual cortex, and tingling in the hands and feet when the wave is in the motor cortex. Once the wave passes by, the nerve cells become quiet and spent.
In fact, the main focus on Melinda Beck's article was on a phase even before the aura, which again precedes the headache phase. In the so-called prodromal phase subtle symptoms can start several hours or even the day before the attack. Problem is, these symptoms may only be apparent when one looks back on an attack.
The problem in research lies in the question How do these phases relate? Is one causing the other? Or are all caused by a common source triggering all these in a sequence.
The brain stem is often accused of being the culprit. But even if so, is an event (which?) in the brain stem the beginning of a chain of four subsequent pathophysiological reactions that correspond these four migraine stages or does this mysterious event rather conduct this sequence of migraine phases. Or a combination of both? Many researchres search for the mysterious conductor of a neural orchestra playing migraine.
By the way, this topic turned in the FOX News into an article "Migraine Sufferers May Be Able to Stop Attacks Before They Begin". It cites The Wall Street Journal citing experts. Confusion, right? Stopping something before it starts is simply preventing. So some like to prevent the conductor waving his baton. That is difficult if you don't know who the conductor is. Or, to quote Melinda Beck again, in the prodromal phase it is just "all the kind of motherhood and apple pie advice" that is all a migraine suffere can and should follow, even more stricktly than without such subtle warning symptoms. Once we know the conductor, we could do much better.
Thus, the questions I raised above are the ones we have to answer first to get towards the new way of treatment. Thinking about mathematical ways to achieve this, that is, to explain how the phases of migraine are bridged, is clearly going beyond motherhood and apple pie. To my (again biased) mind, the key to migraine is in the aura phase.
In this scheme, there is no conductor. I once heard the that "the brain is playing jazz", I can't remember, who said that, but this is the way I look at it. A self-organzing pattern formation process that needs to be controlled.
"Migraine and cortical spreading depression" is the topic of a special Pre-Congress Symposium that I organize together with colleagues on the IHC2011. Cortical spreading depression (SD) is the wave causing the aura and—this now is a hypothesis—cortical spreading depression is causing in a certain chain reaction the delayed migraine headache phase. That is what I will present on the IHC2011.
I also will keep you posted in this blog about how mathematical modeling may support this view, help diagnosis, and maybe even improve one day the migraine treatment.
Note
On June 10, I did an small update this post, including two more figures and explaining in some more detail what I call the conductor and the SD theory of migraine.
The Wall Street Journal video, click on the image to start the video in its own window
I love the image, too! I thought the entire article was extremely well done. I only wish the headline writer had used the word migraine instead of headache in the WSJ article.
Good point. The WSJ article is indeed about migraine only, while the meetings, the past and upcoming one, are more generally on headaches.
The problem starts when often people do not distinguish and take any headache for a migraine.
Thanks, Markus, for the great explanation. To clarify one point, are you suggesting that the aura phase exists in all migraineurs? And its manifestation is perhaps too subtle to notice in milder migraine? Or are you saying that you believe the aura phase contains the answers to averting migraine before the pain phase? Or perhaps something else?
The hypothesis, which I follow at the moment, is indeed that the aura phase, or rather spreading depression (SD) exists in all migraineurs. Sometimes SD can be without symptoms (silent aura). It can be either just unnoticed or really not present due to the brain's ability to compensate for the temporary lost function.
There is some clinical and experimental evidence, mainly from the lab of Michael Moskowitz in Harvard, while I work on theoretical models explaining this and making further predictions on the spatio-temporal dynamics of the aura that need to be tested in clinical trials using functional imaging.
Melinda Beck's explanation of cortical spreading depression (CSD) is wonderful. We now know CSD plays just one part in Migraine, but also learned at the AHS meeting last week that the Thalamus may play a role in Migraine along with genes and their mutations.
I'm not sure I'm clear on your thoughts regarding "is indeed that the aura phase, or rather spreading depression (SD) exists in all migraineurs". I understand the CDS involvement, but from your above explanation, how is it that 'all Migraineurs' have aura when most of the current data shows around 25% do? Your graphs are interesting, yet I don't see the general connection that we all experience aura? Could you explain it a bit further for me?
Prodrome on the other hand, is probably experienced by most all Migraineurs, they just aren't aware of it. As we saw at the AHS meeting yawning, excessive urniation and fatigue are all symptoms of prodrome. During this phase we may be have an increased sensitivity to our triggers, light, sound, smells and what not. But isn't that what a Migraineurs brain is in general? More sensitive to stimuli than "normal" brains?
I think a bigger problem is reversed - more people think they have a headache when they really have Migraine. With 37 million people affected by Migraine, how can that not be true?
Thanks for a thought provoking article.
Nancy
I hope, I find some time soon to write more about the silent aura, i.e., a migraine without aura but caused by SD.
For the moment, I must refer you to an article by Cenk Ayata [1].
From the abstract: "Here, I will review the accumulated evidence supporting a causal relationship between SD and migraine aura and headache, and discuss the contested notion that SD may also be involved in migraine attacks without a “perceived” aura."
You may also look at these figure from a blog post in German "Unbemerke Aura" (silent aura).
"Auslöser" is "trigger"
This is a simplified version of the schemes above and taken from [1]. Together with Cenk and another colleague, we are organizing this Pre-Congress Symposium."Kopfschmerz" is "headache"
References
[1] Cenk Ayata, Cortical Spreading Depression Triggers Migraine Attack: Pro, Headache (2010)
By the way, I, and it seems others too, use CSD (cortical spreading depression) and SD (spreading depression) interchangeably.
I prefer SD, as SD can be observed in any gray matter (hence the blog name ..., well also for other reasons). In migraine, SD usually is in the cortex. So the additional "C" for cortical SD is also correct.
Now this is a bit embarrassing. I really forgot about my own blog post from Jan 1, A deluxe brain feels no pain. There, I already explained some more details and used the images above in the original English version.
I found this post in Google today. As I said, it is a bit embarrassing. But thanks, Google! To my defense, I remembered to Germam blog post and most of the time, I have only one version of my posts.
Recently diagnosed "migraine aura with/without headache". Totally confused.I have no visual symptoms other than floaters, & must keep eyes closes while turning head. Was taken to ER by ambulance 12 days ago. Dr.'s thought I had a mini-stroke. 3 CATS clear, 1 MRI negative. Suffered with migraines since 12 yrs old (63 now). Have been experiencing facial & mouth numbness for a month, now total numbness on right side. I am also diabetic. Almost off diabetic meds now. Was being treated for autonomic nueropathy. I do not know who to believe. Constant ringing in ears & no headaches. Heart tests fine, no blocks. Am lost. Trying to log food intake, but so far, no results there. Any advice? ANYONE?