A 50-year-old woman has been referred to a neurologist because of severe headaches. She first developed headaches during adolescence, and they worsened in the setting of menopause. A typical headache is unilateral and localized to the right frontotemporal and periorbital regions. The pain is described as throbbing and pulsating which is rated 9/10. When severe, her headaches are associated with nausea, vomiting, photophobia, phonophobia, and visual symptoms, and decreased physical activity. She has at least 8 severe headaches a month which can last anywhere from 4 to 48 hours and cause her to miss work. She currently takes ibuprofen and acetaminophen which only mildly help with her pain. Her examination was normal. Blood work and MRI of the brain were normal.
Chronic Headache Diagnostics: When the MRI is Normal
Dr. Gudin: This sounds like a challenging yet fairly typical case of a patient with headaches, so let’s start with the MRI results, which were normal. I’ve had countless patients with really severe refractory headache syndromes that we send for MRI and they come back normal. Can you give us an idea about the pathophysiology of headache and migraine in particular, and why MRI might be normal?
Dr. Argoff: What we now know about migraine headache is that migraine is very much linked to intrinsic changes and excitability changes within the physiology of brain circuitry – and not necessarily structural brain abnormalities. And so, one would expect that what’s going on in someone’s migraine brain is a physiological event but it’s a wiring and neurochemical issue, which is an important discovery because, as we will discuss here, this has led to incredible advances in therapeutics.
Most people who experience migraine will not have an abnormal MRI and there are even some organizations that have recommended against obtaining MRIs on a routine basis if you think the diagnosis is migraine.
It’s important to note that the presented case is a 50-year-old woman who has gone her entire life on very minimal treatment and yet, her life is being impaired. When someone presents to you in mid-life with severe headaches and has never been imaged before, it may be very important – even if the MRI is likely to be normal – to screen and make sure it’s normal.
Migraine and Mental Health: Suicidal Ideation and Risk
Dr. Fudin: It would seem to me that there’s a very high risk in patients like this, who are resistant to a lot of therapies, for suicide. Can you comment on suicide risk for chronic migraine and for patients who have facial pain compared to other pain disorders?
Dr. Argoff: We were just talking about this with respect to the suicide risk of trigeminal neuralgia patients. In fact, a patient had bought a handbook from a trigeminal neuralgia association and was scared because the suicide risk for that population was listed pretty high – like 10 to 20% –that’s not how many people die by suicide but, rather, how many may think about it.
Dr. Fudin: Frustration has got to be high among these patients, as I know it’s high among my patients… and suicidal thoughts are just one of the reasons, along with rebound headaches, why we will not use opioids in such patients.
Dr. Portal: I can add that a lot of patients with migraine do have comorbidities of psychiatric illnesses such as depression and anxiety, but there’s no concrete evidence that there is a connection between psychiatric illnesses and migraine headaches.
Editor’s Note: See a special series on the overlap between mental health and chronic disorders, including a Q&A with pain psychologist Robert Twillman, PhD, and a look at gaps in depression screenings with pain practitioner W. Clay Jackson, MD on our sister clinical site Psycom Pro.
Migraine Pain: The Myth About Bilateral Presentation
Dr. Gudin: Returning to the case, this patient’s headache is unilateral and localized to certain parts of the cranium. Is that common in migraine? What should clinicians pick out of this case that might point them to understanding whether this is a typical migraine case or perhaps related to another cause?
Dr. Portal: A lot of features of migraines are unilateral in nature – they do have those throbbing, pulsating features and can be very severe headaches associated with other side effects such as photophobia, phonophobia, nausea, and vomiting. However, we see in our everyday clinic that not every single patient that comes in with migraine headaches presents with these symptoms. A lot of patients have bilateral headache presentations that can be anywhere in their head – frontal, occipital, or top of their head – and some have severe associated symptoms like nausea and vomiting while others have auras. We see a whole gamut of presentations.
Dr. Argoff: To add to this, we see people who have bilateral headaches that worsen with head movement – they occasionally get nauseous, they sometimes get light-sensitive – but they’re told they have tension headache. They’re told they don’t have migraine because it can’t be migraine if it’s bilateral and that’s not true – over 40% of people who meet migraine diagnostic criteria do, in fact, have bilateral headaches.
Headache Days: One Crucial Question to Ask Patients
Dr. Gudin: While we’re discussing migraine diagnostic criteria, I noticed Dr. Portal talked about the number of headaches a month that the patient experiences, as well as how long the headaches last. What factoids may or may not lead toward a diagnosis of migraine?
Dr. Argoff: Migraine typically lasts several hours to several days and the frequency of migraine headache actually helps us to understand the impact on that person. Episodic migraine, in general, means that a person has between 4 and 14 headaches per month, whereas chronic migraine is 15 or more headache days a month. A really good question to ask a patient, however, is not is not only how many headaches they get a month, but how many days within last 30 days were they completely headache free. A lot of people will not tell their provider whether or not they’re experiencing other headaches – they only tell you about the severe headaches. And many people will have milder headaches that are not as severe in terms of nausea, etc, and that’s super important to know when it comes to treatment selection.
For example, this person presented may very well have chronic migraine. In this case, she’s reported having 8 days of headache but she hasn’t told us about the other days yet.
Framing a Migraine Treatment Plan: Why the Older Agents Are No Longer Used
The benefits of using CGRP antagonists, gepants, and ditans
Dr. Fudin: Considering the CGRP antagonists and gepants, where would we start treatment with a patient like the one presented? Could you frame a treatment plan in chronological sequence?
Dr. Argoff: This is a really interesting question because we struggle with this. The last time the American Academy of Neurology published guidelines about preventive medicines (which I happened to be a co-author of) was over a decade ago. In those guidelines, things like topiramate, valproic acid, various beta-blockers, and tricyclics were first-line treatments.
We learned that other treatments at the time, like Onabotulinumtoxin-A or Botox, weren’t there yet in terms of quality of studies, so they weren’t recommended.
But when you look at those other classes of medicine – they are not always well tolerated. About 80% of people may not be taking those medicines 12 months after they start them … think of the side effects, for example. Fast forward to 2018 – for episodic migraine – and suddenly we have three or four monoclonal antibodies to a specific neurotransmitter, CGRP, that is known to be a major player – an evil neurotransmitter, so to speak – when it comes to the pathophysiology of migraine. These medicines have side effects that are primarily based in adherence rates and tolerability – they’re not 100%, but they are much better than oral medicines that you have to remember to take on a daily basis. (See also, CGRPs antagonists for non-migraine indications)
So, I would say, and Ben can comment as well, I think we’ve moved away from initiating people on the older medicines because they’re not as likely to work and they’re also not as likely to be taken as prescribed. I would imagine that many of our colleagues around the country have found that the newer agents seem to be much more tolerable … and people are taking them.
Dr. Portal: I agree 100%. Patients are thrilled to be on these newer agents from my experience. They just need to dose once a month, and when I follow up with them every 4 or 5 months or even a year later, patients are still on the same medication.
Another great thing about these new agents is that there’s also abortive therapy that uses the same pathway – so even if they have a pain flare or migraine headache in the month where they’re on their monthly dosing, there are other oral medications they can take and get pain relief very quickly.
Getting the Full Patient Medical History
Dr. Argoff: So, a typical scenario with the presented 50-year-old female might involve the clinician asking, Have you ever used a preventative medicine? “Well, I tried a couple of things and they didn’t work,” she might respond. What did you try? “I don’t remember or I tried something and I couldn’t tolerate it or it didn’t work.” Then you will say, Well, why are you only using ibuprofen, or acetaminophen, something specific. “Well I can’t tolerate the triptans and make they make me feel funny…’
Many people are on the butalbital-acetaminophen-caffeine combination, or the acetaminophen-caffeine form – and you mentioned opioids, Jeff – those are the main reasons people experience medication overuse headache. When patients say, “Well, the only thing that helps me is butalbital so I have to take it every day,” that can worsen and intensify things. So, the availability of these newer agents for chronic migraine plus the availability of Botox, and the fact that you can use Botox and CGRP monoclonal antibodies together, and use other medicines that do not cause medication overuse headache for abortive therapy – that puts us in a whole different category of having tools in our toolbox that aren’t going to be harmful.
And Ben, who is an anesthesiologist by training and is very comfortable and familiar with treating someone who has a bad headache in the middle of this great prophylactic kind of experience – can do occipital nerve blocks, find a new cervicogenic source of exacerbation –
Dr. Portal: Yes, it’s always important to evaluate the patient to see exactly where their pain is and we can offer other diagnostic and therapeutic injections. If pain is mostly in the back of the head, it could likely be secondary to occipital neuralgia and we can do occipital nerve blocks.
It can be cervicogenic or my myofascial related or facetogenic….
Dr. Argoff: …So you suddenly have all these people who are able to function, to more feel more comfortable staying at work, they don’t have to go down for the count.
And if they do, there are still other treatments including new ditans – lasmiditan is now available (you can’t drive after taking it so it’s not a drug to use while at work) – but it’s another medicine that could be used in concert with all these things. So, it’s a strange thing to say, but it’s never been a better time to be a migraine sufferer because of all the new options that are available.
Nonpharmacological Approaches to Migraine
Dr. Gudin: Let’s shift gears and discuss briefly what nonpharmacological approaches should be considered for patients with migraine.
Dr. Argoff: Acupuncture and certain supplements, such as coq10, riboflavin, and magnesium can be used but it’s also very important to know that there are now several FDA-approved electrical devices, including a super orbital nerve stimulating device (Cefaly) and one that uses the principles of conditioned pain modulation (Nerivio). These approaches can be used as adjuncts.
Other nonpharmacological approaches include, as Ben mentioned, occipital nerve blocks to abort a headache, interventional approaches… There are so many creative, well-established approaches.
Dr. Fudin: Charles, what about diet in terms of any benefit to people with chronic headache and migraine?
Dr. Argoff: Absolutely, if someone has a particular dietary trigger that’s part of their headache history – for instance, we know about menstrual triggers and those who may be sensitive to gluten. However, we’ve learned that when people get their headaches under control, some of these newer agents allow people to eat with freedom – for instance, if they occasionally want to eat a bagel, suddenly that doesn’t trigger their migraine, and so people feel in many ways liberated with the newer therapies.
Chronic Headache in Primary Care: When to Refer
Dr. Gudin: Before we close, what can primary care clinicians do initially with headache patients and when should they refer a patient for specialty management?
Dr. Portal: Initially, they should always do a thorough workup, including bloodwork, to look for red flags and to check for any metabolic or infectious etiology which could be causing headaches. With migraine, there’s no diagnostic test so it comes down to the history, physical, and excluding of other diseases.
Dr. Argoff: I’d add that we all practice in different geographic and practical settings. And so, if you’re a primary care provider and you’ve identified that a person has migraine (use the ID Migraine screen) and you know that, in your practice setting, you’ve done all you can do… develop a relationship with the headache specialists and neurologists in your community who can see your patient sooner. Not addressing migraine early can lead to impairment, disability, despair, and negative changes in people’s lives. So, know the limits of your practice, know your resources, and get that person the right treatment as soon as possible.