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Migraine Headache and Advances in Management · Pediatrics Now: Cases Updates and Discussions for the Busy Pediatric Practitioner

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I'm Holly Wehment, and this is Pediatrics Now, cases, updates,
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and discussions for the busy pediatric practitioner.
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This talk is from our Pediatric Grand Rounds.
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Pediatrics Now is brought to you by the Department of Pediatrics at UT Health
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San Antonio and University Health's new Women's and Children's Hospital. Let's listen in.
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And thank you for attending Pediatric Grand Rounds at UT Health San Antonio.
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Our speaker today is Dr. Azra Akbar.
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It's my pleasure to introduce Dr. Akbar. She is an associate professor in the
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Department of Pediatrics.
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She is our pediatric neurologist, epileptologist, and headache management specialist.
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Dr. Akbar received her medical degree from Dow Medical College in Karachi, Pakistan.
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And then after moving to the United States, she did her residency at Cardinal
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Glennon Children's Medical Center in St. Louis, Missouri.
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After that, she did her Child Neurology Fellowship and Neurophysiology Fellowship,
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UT Southwestern, followed by her Headache Fellowship and Allison Headache Management
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in Baylor, Dallas. That's a lot of fellowships.
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And then Dr. Akbar's faculty at UIC in Peoria before coming to UT Health San
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Antonio in February 2024.
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Thank you so much. Thank you for the introduction, Dr. Raj. I appreciate it.
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Okay. Can you, I can see my slides. Should I just start?
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Yes. Okay, sounds good. All right, thank you again.
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So the objectives for this talk are to talk about common headache disorders
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in the pediatric population, and the most common would be migraine.
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Migraine without aura could also be migraine with aura.
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I'd also talk about other headache disorders that we commonly see,
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including chronic daily headache, chronic migraines, and most importantly,
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medication overuse headaches, because that is preventable.
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And quite difficult to treat if it comes on and is not treated appropriately at the right time.
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Other factors contributing to migraine and recent advances in management,
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including neuromodulation and injections other than just Botox, the CGRPs.
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There is quite a lot to talk about and it is rather exciting because I think
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oral medications can be quite tedious and there is a risk of medication non-compliance
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in our pediatric population with that.
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So the pediatric migraine, so migraine prevalence in children can be about 3 to 10, 15 percent.
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And out of all the cases of headache encounters that we see in our clinic,
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about 80 percent or more of them, 50 to 80 percent of them are actually migraine related.
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There are other headaches we see, like cluster, tension, sunk headache,
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suna headache, medication overuse, chronic daily headaches, new daily persistent
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headache, which is not as common, certainly.
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Some of them are actually more in the older population anyway.
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So migraine in our pediatric neurology clinic would be the most commonly diagnosed headache disorder.
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And the ratio, as we know, is before puberty is equal, but after puberty,
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there is a female preponderance.
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And the theory with that, we'll talk about that more, is also because CGRP apparently
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is higher It is elevated at the time of migraine, but it's also elevated in the female gender.
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Most patients will continue from their childhood to their adulthood to continue to have migraines.
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And 25% will transition into other headache disorders, but 50% will continue to have migraines.
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I'm just, disclosure, I am a migrainer. And I think the first migraine that
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I've had was when I was five.
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And I've had migraines with or I have a pleated migraine. And I've tried several
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of these medications on myself. And we can talk about that. It's an end of one.
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But still, as a patient, there'll be some, a patient talking as well.
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Okay, so migraine in history, so 1550 BC, apparently that's the first time it
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was described by Evarius papyrus, and bloodletting was a treatment that was
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used. So bloodletting was an Asian treatment.
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Hippocrates mentioned it as also described it then in 460 BC as a bright light in the eye,
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and in 17th century, Thomas Willis founded this vascular theory,
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which honestly, we are still to date this vascular theory about the decrease
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in blood flow or cortical spreading depression as the other term we use is still used.
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And then Mobius, I think this is the doctor from Mobius syndrome,
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1898, who described it as parenchyma is the master and circulation is the servant.
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Took me a little bit to understand, but I think what they mean is parenchyma
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is stagnant and circulation is what makes the migraine dependent on it.
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So when the circulation changes, is the parenchyma suffers the pain.
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These are very interesting theories from centuries ago, but we are still kind
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of working around those theories.
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The first medication for management of migraine was around 1918,
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the 1920, and which, you know, is the DHE.
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And then in the 1980s, CGRP research had started.
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CGRP was discovered as the calcitonin gene-related peptide, which is involved
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in the neurogenic inflammation. These are the theories of migraines that started coming out.
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The International Headache Society, and that has been quoted in this presentation
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many times, and we'll talk about that.
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Their classification started coming out in the 1980s.
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And CGRP research continued.
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Interestingly, it started in 1980s, but anti-CGRP has been approved like literally four years ago.
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So that's interesting, but it is also exciting.
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So again, we'll talk about what exactly is a migraine, how does it differ? How does it differ?
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So migraine is a complex, debilitating, recurrent, multi-system disorder that
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is multifactorial also and has a genetic component.
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I think one important thing to take home from this presentation would be that
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migraine can respond to a single pill, like you can use Eleval,
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Topamax, the proeptidine, which are the most commonly used ones.
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But if it is a chronic migraine and it is multifactorial, which it could very
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well be, that is patients, significant number of patients will have a history
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of depression, anxiety, some other mood disorder.
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You know, psychosocial issues, family history, obesity, low self-esteem, all of that.
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They usually will not respond to a single pill.
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It has to be a multidisciplinary approach. So a multi-center,
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like a headache center where there's involvement of perhaps psychologists,
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psychiatrists, and a headache neurologist, all of that is usually very helpful.
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Also weight loss, lifestyle modification, and using natural substances should
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also be advised other than hydration and adequate sleep.
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We'll talk about that more, but I just wanted to say this, that it is multifactorial
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and migraine is chronic and debilitating and migraine can be pretty stressful to the patient's life.
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Okay, so migraine without aura, and this is the classification that I just mentioned
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according to the International Headache Society.
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This is the most recent classification, and it's published in the Headache Journal of Cephalgia 2018.
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So migraine without aura, so a migraine differs from your other headaches,
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like tension headaches or whatever we'll describe.
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There are five attacks, usually unilateral, usually patients have sat behind
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the eye, pulsating, moderate to severe intensity, aggravated by routine physical activity.
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And during the headache, the patient will have one of the two,
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like either nausea or vomiting or photophobia or phonophobia.
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Usually there's a family history and it's not better explained by other diagnostic criterias.
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Then the migraine with aura is obviously a similar presentation,
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except it comes with an aura, which is gradual, starts with a slow activity
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of five minutes or more, and then will go on from five to 60 minutes.
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And within 60 minutes you'll see the headache and it could be a positive or
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a negative aura and aura would be visual, sensory, speech, motor, brainstem.
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I didn't go into all of the types of other migraine with aura but hemiplegic
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migraine only because I have seen it more here at the center in the past nine
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months that I've been here and also it could be quite stressful because people
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could think it's a TIA or is it not.
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Okay so this is again filling the four criteria that we talked about earlier,
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and an aura, which would consist of both fully reversible motor symptoms and
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fully reversible either visual, sensory, or speech motor language.
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This is, like I said, in 1996 is when the first gene was identified,
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and there are three genes that are identified with it, and that's the CACNA, ATP1A, SCN1A.
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It's interesting because CACNA, ATP1A, as you know, are associated with other
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neurological disorders, SCN1A with other epilepsy syndrome disorders as well,
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but not necessarily, like doesn't mean it has to.
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Okay. Chronic migraine is, I think, what we see mostly in our clinic.
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Patients are usually very appropriately managed by the pediatricians here,
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and then they come to us. Usually we don't see the episodic ones.
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Of course, we see the chronic ones, which is patients having more than 15 days
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of headaches for the past three months.
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Migraine with or out, migraine without, not better explained by,
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and of course, the patient will tell you that they have other symptoms,
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and they respond to the medication, which is used typically for migraine.
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This, I made two slides on it, because I think this is, if there's one thing
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we need to understand from this lecture, well, two, three things,
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but one of the things that we need to understand would be medication overuse
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headaches, because it becomes very difficult to treat, but it is preventable,
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So prevention is better than cure. So preventing it. And how do we prevent it?
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Preventing medication overuse headache is more than 15 days of headaches a month
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over the past three months because the patient is overusing the medications
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for the past three months.
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Some are worse than the others. So if they're using 15 days of,
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you know, the over at the counter and set and all, that's 15 days.
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Okay. But 10 days a month of these ergots, triptans, that's why whenever we
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prescribe the triptan on the script, we write not more than 10 a month.
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So we don't prescribe that much anyways, right?
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Or other opioids, we do not like to use that. Risk of medication overuse is much, much higher.
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And of course, some of these other medications. And this is preventable.
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So how do we prevent it? We prevent it by initiating lifestyle modification sooner.
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And initiating a daily preventative medication if needed, if they meet criteria,
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if they have chronic migraines, sooner, rather than just giving PRN medications
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and they get into the habit of it.
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So the neurons in the brain called the microglia will start to appreciate pain
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more, and it's called central sensitization.
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So it becomes harder and harder and harder.
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And when the patients come to us and we tell them, don't take your Tylenol that
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you're taking every day, that kind of really upsets.
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It can be quite upsetting because it helps them at least for the first few hours.
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So it's intimidating for them to just stop the medication.
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This slide explains the pathophysiology of migraine as well as the other two
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slides. The pathophysiology of migraine is thought to be initiated by the hypothalamus,
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which is the early phase.
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Hypothalamus apparently will cause the premonitory phase and then activation
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of the trigeminal vascular system.
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Which is the trigeminal nerve, which is the big, you know, the nerve that decusates
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into the brainstem and then projects to the thalamus, which is involved in the
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propagation of migraine.
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And the term they use is cortical spreading depression, CST.
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Stages of migraine, not necessarily, but a lot of people will have that prodome and aura.
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A lot of people will actually have yawning also as before their migraine starts.
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So this is kind of what we had talked about in our second slide that mentioned
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even in the 17th and the 18th century, when they said the parenchyma is the
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master and the worker is the, I think this is what they meant by the vasculature,
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because the blood flow is decreasing is the thought.
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The term they use is cortical spreading depression, which is depolarization
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and decrease of blood flow followed by a period of hyperpolarization.
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And that is two to six millimeters per minute.
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Another slide.
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Okay. This is another slide that explains this better.
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That is the brainstem pathway that modulates the sensory input.
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As you can see over here, these are the trigeminal, these are the meningeal vessels.
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And these meningeal vessels pass through the trigeminal, go through the trigeminal nerve.
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And as they pass through the trigeminal ganglion, they synapse over here in
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the midbrain or the pons, and they decusate over here, second-order neuron,
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and then third-order neuron goes to the thalamus.
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But over here, they also decusate and they project into the superior salvatore
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nucleus, which is involved with lacrimation, etc.
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So people who have a stronger arc between the trigeminal ganglion,
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and superior salvatore nucleus are the ones that have the trigeminal autonomic
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cephalgias, which includes trigeminal neuralgia, if you've seen it,
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or sunct or suna headaches, or even cluster headaches in which they will have
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tearing from the eye and injection from the eye and other signs like that.
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As pediatric neurologists who also manage headaches, in our clinic template,
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usually we also include this in our template, actually, and we like to talk
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to patients about this, families about this.
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A lot of times, a smaller child, a younger child will maybe have migraines, but they can't speak.
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So colic, infantile colic, certainly, abdominal migraines, and they can evolve
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into cephalic migraines later, cyclic vomiting, et cetera, benign peroxis,
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well, vertigo, actually bed wetting, nosebleed, teeth grinding is also included,
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which is not mentioned here.
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I've talked to my other, my senior colleagues, especially Dr.
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Gross and all, and they've been managing patients with headaches for quite a long time, pretty well.
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And they've also mentioned cyclic vomiting and abdominal migraines, et cetera.
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So working hand in hand with other subspecialists, for example,
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PEDS-GI would be very helpful.
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And at the center, we do a pretty good job, all of us at that.
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PEDS-MIDAS, this is reported in a lot of studies.
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Whenever we are doing objective data classification, comparing Topamax or amytriptyline
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or Botox, and you want to see, did it work, did it not, headache diary is great,
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but this is a very objective method and this is quick.
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We give them to the, we give it to the families in clinic and they fill it out.
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The higher the score, obviously, it's not good, small, better score is,
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you know, it just asks you how many days in the past three months you've had
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an improvement or worsening.
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How many times did you miss time or school or other activities?
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Prodomal symptoms are actually quite common in our children.
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And children with headaches, like we've talked about before,
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that's why we keep talking about lifestyle modification and not just a single medication approach.
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A single L-level or single tokamaks approach will probably not be effective
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if it's pretty intense chronic migraines.
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So looking at other risk factors and why they are there and if they can be addressed
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and how they can be addressed, that's why a multidisciplinary,
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multifactorial approach would be good.
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So screening them for anxiety and depression is very helpful.
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We work well here hand-in-hand with the pediatricians also.
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The PHQ depression assessment, and there are, of course, several other tools
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that the PCPs here use and very well managed.
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Otherwise, this is a good slide because a lot of times patients will come and
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they will ask why my MRI is normal, but why am I having this?
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So it's great that the MRI is normal.
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And usually in a migraine, the MRI would be normal.
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Because it's a diagnosis of exclusion, remember? So the things that are associated
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with it could be genetic.
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As we know, quite a few genes have been identified. The first one was in 1996
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for the amoebligic migraines, which was a long time ago, 1996.
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Environment, stress, elevation height, diet, exercise, keep talking about that,
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diet and exercise is very important.
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And menstruation, pregnancy. After menopause, they can get better because estrogen
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can cause more migraines. Estrogen is a pro-convulsant and also can cause migraines.
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So menstrual migraines, a fancy term, is called catamenial migraines.
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And there are some triptans which are long-acting, so they work very well for that.
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And we'll talk about that for cataminin. Because if they don't have migraines
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any time else, they only have it during the period, then we just give that to them.
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And again, this explains the theory that I just went over.
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Hypothalamic activation, cortical spreading depression, and release of these CGRPs.
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CGRPs are important because it's new, it's recently come out,
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it's exciting, so we'll talk about that.
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So the first medication that ever came out was in 1920. T, sumatriptan was approved in 1991.
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Sumatriptan is very well tolerated, but I'm sorry, it's very effective,
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but not as well tolerated as others like MagSalt.
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So that's usually my preference. And then Botox was approved in 2018.
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There was a study called the PRE-EMT trial that included about 1,300 adults,
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and it was over a period of 52 weeks.
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And after that, and that's called the PRE-EMPT trial, and I'll show you slides
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about the 31 site injections.
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And also, Botox actually was first used and approved for wrinkles,
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and it was first approved in April 2005.
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In those time period, people noted that their migraines are significantly improved.
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After that, this PRE-EMPT trial was done, and Botox was given.
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And then in 2018, which is actually much later, so the advances have been between
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2018, I mean, after 2010, there wasn't much after Botox.
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So this is when the CGRP started coming out and the CGRP inhibitors have been approved.
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2019, this lamcy ditin, which is, I'll talk about it briefly.
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This is also new, but it's approved for 18 years and older, overall well tolerated,
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but can cause a lot of sedation.
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And then of course, we'll talk about more anti-CGRPs, which are called G-PANs.
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So the other CGRPs in 2018 that were approved, they are injections in 2019 is
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oral. So we'll talk about that in a minute.
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We'll start by talking about treatment that includes like triptans,
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which most of us who have treated headaches are quite familiar with.
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There are seven of these. The first one that we talk about, the one that's most
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commonly used is sumatriptan. It's fine. It's good.
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But usually side effects are a little bit more, especially nausea or vomiting.
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In about 2015, I believe they came out with a patch, but the batch got significant
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side effects including burning so they withdrew that.
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So now the one that's used, Treximet is very commonly used. It comes with an NSAID in it.
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The one I use commonly, most commonly is this Rhesatriptan Maxol.
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It also comes in oral dissolvable.
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It is approved for children six years and older.
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The other ones are for 12 years and older. So Rhesatriptan really works good
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in my experience and six years and older.
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So the other Everyone's Zolmitriptan is fine. It comes in a spray,
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but then again, then we talked about Zolmitriptan.
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There are other devices that are approved, and we will talk about that,
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which is actually quite exciting because medication needs medication compliance.
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And if the patient is not medically compliant, then that's a little problem.
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So if we have CGRP injections, they're once a month.
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Botox is once in three months. So it's much, much easier to do.
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And these neuromodulation devices that we'll talk about, you know, you don't have to eat it.
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So hopefully this is, and I've had it done on myself. I'll talk about that a little bit.
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So again, just talks about how these triptans are supplied.
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These are usually easily covered by insurance. Most, even patients who come
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to us in clinic have already been tried, have already been prescribed at least
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sumatriptan by their PCP.
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So that's good.
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How do they act? 5-HT1D and 1B receptor.
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1D is involved with the release of neurotransmitters. Again,
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substance P, which is the pain, and the CGRP.
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Again, tryptans act also on the vasoconstrictor through the 1B,
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and they cause vasoconstriction.
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Because again, theory is cortical spreading depression, decreased amount of
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blood flow, so constriction will increase the blood.
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But of course, it can be associated if the patient is older,
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which is usually not a problem, weed counter, but if they have risk factors
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and there's a risk of TIA, but that's in the much, much older population with several risk factors.
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The newest medication that has come out acts on the 5-HT1F, which is the Lamsey-Dytan,
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and we'll talk about that.
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Again, they're all approved for 18 years and older. This is a good slide because
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I think our pediatricians who send patients to us use triptans quite frequently,
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just to know that the half-life of naratriptan and Frovatryptan is very good.
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Frovatryptan is something that we use for catamenial migraines.
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So if there's catamenial migraines, it's only, I started one day before the
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period and I say, take it for the next five days and you just give them six
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or so and it works out fairly well.
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But other than that, Sumatryptan that you already know about,
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but Rezatryptan is my go-to.
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This is a picture I took from my phone and you can see the sunset.
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And this is actually the Illinois River, and this is from my condo,
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and this is UICOM Peoria. This is kind of behind this, this is Caterpillar.
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So that's a view from the winter there in Peoria.
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Okay, so Topamax is one of the other than the neuromodulation devices and the
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PRN medications. This is the daily preventative medication that's approved for
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children 12 years and older.
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And I usually start at 1 to 2 milligrams per kilo, and then you can go up,
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of course. With an older child, you can start at 25.
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Usually, American Headache Society or A and even 75 milligrams total,
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but that's for an adult, usually. Side effects, as you know,
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are word-finding difficulty, weight loss, tingling, numbness.
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Territogenic side effects are also, can be reported. Right hair loss,
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actually, some patients have also told me about that.
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Then propanolol, we don't use it so much in the pediatric population for risk
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of, of course, bradycardia, hypertension.
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Elable imitriptyline is quite often used. And of course, all the dry mouth,
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dry eyes, all those symptoms can occur.
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Depakote works well also for mood. and we can start at 15 or so.
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But of course, you have to look for any kind of mitochondrial disorder if they
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have any of that, weight gain, hair loss, et cetera.
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And of course, teletogenicity, which is important.
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Most of my colleagues at our center, we use a lot of Topamax and our epilepsy colleagues like Dr.
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Linda Leary, who are more experienced in epilepsy, they use that.
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This is great because if the patient also has a history of absinthe epilepsy,
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Depakote is a very good choice. if she's not a female, though, if it's a boy.
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So Depakot is my go-to for that case.
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So Ciproheptidine, I've used it a lot, especially for abdominal migraines and
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L-level. There are more studies on that.
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Lyrica is really not something I use too much because of sedation.
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Too much sedation and weight gain, don't really use that.
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Botox, we'll talk about that more in a minute. There's class one evidence.
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In the pediatric population, though, it is off-label and 75 units to 155.
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The PREEMP trial that we talked about used 155 international units,
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but they also used the follow the brain protocol, which is excellent.
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Follow the brain protocol basically meant that if the patient feels that on
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this site, on this site, they have more pain, you can use more Botox,
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which is left over because a lot will be left over.
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Occipital nerve blocks, I've done that for occipital neuronegia.
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It's very uncomfortable.
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Patients didn't, I didn't really have the best of experience.
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But so now actually we have neuromodulation devices that will address the occipital
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nerve as well as the other branches of the trigeminal nerve.
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So this is great if we can use the neuromodulation devices.
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So this is Botox. Yes, definitely. I would highly recommend that.
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Again, we talk about lifestyle modification.
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Weight loss, regular exercise, hydration, sleep hygiene, identifying triggers,
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eating regular healthy meals, avoiding foods which are processed.
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And processed aged meat, aged cheeses are not recommended.
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Then I highly encourage all of our physicians and our practitioners who manage
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headaches at our center, encourage the use of lifestyle modification and the
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vitamin supplementation,
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coenzyme Q10 and riboflavin, both of them support the mitochondria.
24:49
The concept I think behind this is that migraineurs also have some form of undisclosed
24:54
mitochondrial dysfunctioning.
24:56
And they respond well to coenzyme Q10.
24:59
There are enough studies even on riboflavin that it is comparable to other preventative medication.
25:05
200 to 400, very easily tolerated side effects are it discolors your urine.
25:10
It's also found in food, like in almonds. You can, but a supplementation is
25:15
fine. Coenzyme, Q10, same thing, 100 milligram.
25:18
Magnesium. Magnesium actually is an NMDA receptor antagonist.
25:22
So what it does is that it stabilizes the neural membranes.
25:25
So it decreases the excitability, the hyperexcitability. So magnesium is great
25:30
side effect as diarrhea, as we know.
25:32
Melatonin, there has been some studies on it.
25:35
Most of them will show that three milligram is right, the appropriate dose in
25:39
pediatrics, but in adults. So this works very well for something called,
25:43
Hypnic headaches, which is not seen in the pediatric population.
25:47
So that's why there's no slide on it.
25:48
But hypnic headache is actually a side effect of medication overuse headaches,
25:52
after which the patient is so primed that they wake up in the middle of the
25:56
night with a headache and the MRI is normal.
25:58
These are older people. They respond very well to melatonin.
26:01
Melatonin, it will not hurt. But in adults, of course, you use a higher dose.
26:05
We can use six or nine milligrams. But in children, this is what we would use.
26:09
Mike, I do recommend using something called Mike Relief. It's over-the-counter.
26:14
You can get all of this individually, or you could get Micrelief or Microwint,
26:18
and they're over-the-counter.
26:20
I get mine from Amazon. It's like, I think, $39 or $29 for more than a month's supply.
26:25
And it's one pill, and it has these. It has coenzyme Q10, riboflavin,
26:31
magnesium already in it.
26:33
So instead of taking, you know, just something to think about.
26:36
This is a slide of Alice in Wonderland syndrome depiction, which was actually
26:41
seen a long time ago, but it was also reported after Second World War when patients
26:46
were subjected to trauma, traumatic brain injuries.
26:50
Okay, so again, we talk about Botox. I just told you about the pre-EMT trial a little bit earlier.
26:56
The pre-EMT trial was in 2010, where 1,300 individuals, adults,
27:01
were studied, and they showed a good response.
27:03
So every three months is kind of these injections. there are 31 site injections,
27:09
155 international units.
27:11
How does Botox, like how does this act? It acts on the synaptobreven B or the
27:16
SNAP protein and it cleaves it.
27:19
And this protein is associated with the release of acetylcholine and acetylcholine will not be released.
27:23
And when it is not released, acetylcholine is associated with pain transmission,
27:29
muscle contraction, and also actually CGRP release. So it keeps coming to the CGRP.
27:34
So once we get rid of that, this doesn't happen. So this process doesn't happen.
27:38
So this is the part behind it.
27:40
These are the injection site reactions, the sites that we do.
27:44
I have had Botox done for headaches. And this area is very easy to do.
27:51
I've done it on myself because this is a fleshy, beefy muscle.
27:54
So this really does not hurt.
27:56
When I do Botox or when we all should be doing Botox, I would advise to start
28:02
in this area, in the back, because it's very easy to tolerate for the patient.
28:06
So now the patient starts off better, followed by this, the temporalis muscle.
28:10
And the most painful is actually in this region because this is a tight muscle, right?
28:14
So the headache, the forehead, it does hurt. So you can use other techniques
28:18
like using ice, et cetera.
28:20
But honestly, very well tolerated.
28:22
Usually when patients hear 31 injections, they're like, oh my God, 31 injections.
28:27
But really, they're like an acupuncture needle, very easy to tolerate.
28:32
And like I said, it's really worth it because if it works for you,
28:35
it's every three months. And if you can get rid of the daily medicine, that would be great.
28:40
This is the protocol. This is what they used, how they described it,
28:44
and the preempt protocol.
28:45
However, the good thing is that they used follow the brain protocol,
28:50
which means the leftover Botox, whichever is leftover because 155 units,
28:54
45 is leftover because it's 200 nitrogen units.
28:56
You can give it, you know, spread it out to whatever the patient prefers for
29:01
the management of their headaches. So there are about between 2021 to now,
29:07
there are 18 studies on children.
29:09
We published this at my old center. We studied this on about 34 patients and
29:15
they had an excellent response to Botox. and most of them, but they were my older kids.
29:21
They were 15 and older. And by the time this was completed, they were already 18.
29:24
And there are, of course, other studies too. So now there are about 18 studies
29:28
on Botox for adolescents.
29:32
It's hard to get insurance approval, but as long as we document that the patient
29:36
has been tried on two classes of adequately tried doses of medications,
29:42
including a beta blocker or a tricyclic antidepressant,
29:45
and they have been tried for the past three months, they continue to suffer,
29:48
They have more than 15 days of headache a month for the past three months.
29:53
Hopefully we can work on it. It takes about two months to get that approved.
29:57
This is my niece. I have three nieces, but this is one of my niece, Barbara.
30:02
We talk about anti-CGRP. So again, even in the other slides,
30:07
we've talked about CGRP because it's one of the more newer, more exciting other than neuromodulation.
30:12
So CGRP is the protein that is released from the nerve terminals for propagation of pain.
30:18
It is a vasodilator, and it's also pro-inflammatory. The drugs,
30:21
and it's been studied since 1980s, as I spoke to you about it in the earlier
30:25
slides, The medications have come out in 2018 and 2019. The research has been ongoing.
30:29
So there are some which are called G-pans, which is the Ubrel-V and the Rima
30:35
G-pans that we have commonly more easy to use.
30:38
So those will directly block the signal.
30:41
They'll directly block the receptor. And they are oral.
30:43
They're a small molecule oral, so you can give that. The other ones,
30:47
which are the other anti-CGRPs, for example, Amovig, Ajovi, et cetera,
30:52
Amgality, they are injections and they are just once a month injection usually.
30:57
With some, you'll give a loading dose, but not others. Yeah,
30:59
so I just talked about it, right?
31:01
Ajovi and these are the ones at the bottom. These are the injections and the
31:05
ones at the top are the oral ones.
31:07
And the injections are just once a month. So the Amovig was approved in 2018.
31:13
HOV was approved also in 2018 M-Galitine 2018
31:16
and then there's a newer one which I actually have not used in
31:19
2020 but I have used Amovig and M-Galitimol and the G-Pants which are the oral
31:25
ones which are the direct receptor blockers they are and you have the three
31:30
kinds right the Rima G-Pant and the Ubra G-Pant and the Ziva G-Pant is a nasal
31:34
spray I haven't used yet there are no studies no published data on children yet,
31:40
Okay. But there is a consensus statement that we can use it if everything else is failing.
31:46
And I have used it. And not only I have, Dr.
31:49
Brian Fox has used it quite frequently. I think Dr. Gross has too.
31:54
And I've had a very good response to this.
31:57
Ubrelby, I just talked to you about it. This is the oral, right?
32:00
The GPED, 2019. So this more recent, EnderTech 2020.
32:04
All right. The other ones I haven't really used so much. The most recent is
32:08
this nasal spray, the Zabzri Prat.
32:11
Clinical trials are underway, but there are expert consensus guidelines, okay?
32:16
And we can use it just like Botox, even though it's for 18 and above,
32:20
we have used it and we've had some good studies to prove our results.
32:25
Then we talk about something even more newer, something less invasive and something
32:29
you don't have to take every day.
32:31
They're definitely not my mouth. So no systemic side effects.
32:34
So remote electrical neuromodulation. There are several types.
32:37
I'll talk to you about it, but this is the most commonly used one.
32:40
I know at our headache center, Dr. Gross and Dr. Fox, they have used it. I have used it.
32:44
We've had a good response. This is pretty simple.
32:48
You don't even like literally you just sign it off. Formal prescription doesn't
32:52
even need to be done. And it's $49 for this.
32:55
In June of this year at the American Headache Society conference, I had it done on my cell.
33:00
As a migraineur, I feel like it was pretty effective. You can use it as needed,
33:04
but also as a preventative for about 30, 45 minutes or so. It's to your phone and it's an app.
33:10
It's for $49, but you can only use it, I think, 12 times and then you need to
33:15
buy another one. It's like $89, but you get a discount if you have three of them.
33:18
This is rather better tolerated and easier to do.
33:22
So this is using neuromodulation, electrical neuromodulation.
33:27
This is also FDA approved, but this is a magnetic stimulator,
33:31
transcranial magnetic stimulator, and it's approved for prevention as well as migraine with aura,
33:37
which is good because migraine with aura doesn't really, you know,
33:40
there's a lot of concern about using tryptan with that, even though the statement
33:44
for migraine with aura is that tryptan can be used unless the patient has other
33:48
risk factors predisposing them to a TIA,
33:51
like oral contraceptive pills or other risk factors like cardiac problems.
33:55
But anyways, so this is something, and I've had it done on myself. It was pretty good.
34:01
Trascutaneous vagal nerve stimulator, as you already know, vagus nerve is the
34:04
largest nerve. Goes from the brain all the way down to the gut.
34:08
Vagal nerve stimulator has been used for epilepsy for quite some time.
34:12
This is just kind of stimulating the vagal nerve. You use a goop and then you do this.
34:16
In my reading and listening to several lectures, apparently the VA uses this
34:22
a lot for episodic cluster headaches. And this is great because in the past,
34:26
what was used for cluster headaches, right? So many people coming in, no oxygen.
34:30
So that was hard. So apparently this is working very well for our older male
34:34
population or even our middle age population for cluster headaches.
34:37
For in children, I have not used it yet.
34:41
These are not as easy to obtain and we really need to do a lot of lobbying to
34:45
work with insurance companies, but it is approved for age 12 and 17.
34:49
Cephali, these are non-invasive external trigeminal nerve stimulator.
34:54
I have as a patient, and I speak not as a doctor, I speak as a patient.
34:59
I've had cephali used on my cell, but that was a long time ago,
35:02
and it was quite uncomfortable because you could feel the buzzing sensation
35:05
when it was trying to hyperstimulate the trochlear, the supraorbital nerve.
35:11
So it was quite irritating.
35:12
And that is what in the following years most patients have said. So cephali is very easy.
35:17
It is $400. You don't even need a script for it. You just go online, you get it.
35:21
And you use it as needed, but it really does need a lot of getting used to.
35:26
Yeah, so most patients I feel were not very compliant, even though it was so
35:30
easy to do. Then there's a new one, Relivion.
35:34
Relivion apparently is much less uncomfortable, but it's harder to obtain and
35:40
it's a little bit more expensive. I think it goes in the thousands, 1,000 something.
35:45
And the thing is that not only does it stimulate the front, it also stimulates
35:50
the occipital area, so the occipital nerve.
35:52
Most patients, what I've heard, will say it is much easier to tolerate.
35:57
Again, these are the neuromodulation devices that we talked about,
36:01
and this also tells you the price.
36:03
See, Cephali is $430, and Nerevio is $49 for the first device and then onwards.
36:11
So this is not bad. These are just some things to think out of the box when
36:16
the patient is medically refractory.
36:19
They've tried amitriptoline, topamax, then you gave zonosemide,
36:22
they're still having, and then they're also taking Tylenol every day.
36:25
And now they have medication-overused headaches and it's just not working out.
36:29
Instead of giving another pill, think about Botox, think about CGRPs,
36:33
and of course, these other devices as well.
36:36
So the International Headache Society's statement is that the neuromodulation
36:40
devices modulate the brain activities, spinal cord, peripheral nerves by means
36:44
of different methods, including electrical current, magnetic field,
36:48
and other device-mediated modalities.
36:51
Oops, I missed a slide. This is a very important slide. Thanks to Dr. Fox.
36:59
So CHAMP trial, which was in 2017, this is a very important thing because this
37:05
was a big study that was being done on children comparing the two most prescribed
37:09
medications for headache,
37:11
amitriptaline and topomec, and
37:12
comparing them to placebo, and it was found that this had to be aborted.
37:16
Because they found that these medicines were no better effective than placebo was.
37:21
And patients actually had a high placebo response rate, which again comes to
37:26
the point about how effective will a single medication be for a patient who
37:30
has migraines, but he doesn't just have migraines. It is multifactorial.
37:34
He also has depression, anxiety, school stress, family history of migraines.
37:37
He has a poor diet. He doesn't sleep well, and he does not eat well,
37:41
and he does not exercise at all.
37:42
And he's depressed. So usually just this one pill will not work very well.
37:46
So placebo, working with other modalities, including massage,
37:50
acupuncture, et cetera, diet, exercise.
37:53
So those were the outcomes. Exercise is important.
37:57
I mean, the old theory is, yes, it releases beta endorphins,
38:00
which are your happy hormones, natural hormones. But also what kind of exercise?
38:04
Weight training, weight lifting, increasing lean muscle body mass,
38:07
because there's a direct association with improvement of headaches with increase
38:11
in lean muscle body mass, as well as with weight loss. Lean muscle body mass. Yeah.
38:18
So a lot of patients will say that when we exercise, our headaches get worse,
38:22
which is possible certainly because migraines get worse with routine physical activity.
38:26
So don't really exercise during a migraine, but it's also a protective mechanism.
38:31
And the theory is that because of the production of lactate also, this can happen.
38:34
But regular exercise during periods of relatively low frequency of migraines
38:39
or a dull headache, not an acute status migraines, is highly encouraged.
38:43
And regular exercise as well as increasing lean body muscle mass is highly recommended.
38:48
Interestingly, AAN's guidelines is the first line treatment is ibuprofen,
38:52
which is, I mentioned that because that is how most of our pediatricians here treat the patients.
38:57
And when they come to clinic to us, this is kind of what they've been on.
39:00
I just wanted to include this slide. This is approved for 18 years and older.
39:04
There was an earlier slide on triptans that mentioned how triptans act.
39:08
So the ditans also act like the triptan, except they don't cause vasoconstration.
39:13
They act on 5-HT1F, not 1B, because 1B is where it causes vasoconstriction.
39:18
So they do not, which is great.
39:20
But there's a lot of sedation associated with it. It's usually in A.
39:24
I've seen it being used in the older population, but so they can become very sedated and driving.
39:29
It's something I've not so far used DITIN for a pediatric patient yet,
39:34
because I have so many other interesting toys right now to play with.
39:37
So it's like, you know, I've got so many choices now.
39:40
So tryptans, you already know about. Dytans, we talked about.
39:44
There's just a slide going over.
39:46
You know, G-pans are the oral CGRPs.
39:49
And the monoclonal antibodies which you know about are your injections.
39:52
And of course, Botox, I am a big proponent of that.
39:55
Side effects, of course. Anybody can have side effects. I've had side effects.
39:59
Botox can cause like muscle twitching, but it can cause injection side reaction.
40:03
But the most common side effect of CGRPs is injection side reaction.
40:06
With Botox, really, ptosis sometimes, you know, asymmetric maybe,
40:10
but other than that, Botox is well-tolerated otherwise.
40:13
Propanolol, I don't use too much, and Elival and Topamax are the most commonly
40:17
used, followed by maybe Depakote.
40:20
A lot of people will ask, like, when do we image? Do we image?
40:23
So do we get brain imaging? So the AN guidelines are, you know,
40:27
the chances that you'll actually pick up on something that surgically needs
40:30
correction is less than 2% or so.
40:32
And there's a Choosing Wisely campaign that said that neuroimaging is only needed.
40:35
Of course, if there are focal neurological findings, not anybody and everybody
40:39
needs head imaging and most people with headaches don't really need an EEG unless
40:44
you're suspecting something like Penetopolis syndrome or one of those other
40:49
seizures disorders like gastro syndrome or, you know,
40:52
in which there's prolonged retching and dysautonomia. But other than that, not everybody needs it.
40:56
So this is from the ANS guidelines. I would like to thank our wonderful team
41:02
for their help with patient management, their excellent care,
41:06
and actually helping with this slide presentation, Dr. Fox, Dr. Sheldon Gross, Dr.
41:11
Linda Lary, Dr. Natasha Varghese, Dr. Daniel Lapid, Dr.
41:14
Nicole Lavin, Dr. Daniel Lanigan, Mrs.
41:18
Sandra, and our admin support clinic nurses, and most importantly,
41:21
our patients without whom there would be no presentations and really nothing to talk about.
41:28
So thank you very much. I think I'm on time or maybe even faster. So any questions?
41:35
Dr. Akbar, thank you for the wonderful presentation. From the audience,
41:40
if you have questions, you're free to place them in the chat or you can raise
41:44
your hand and unmute yourself.
41:46
I guess while we're waiting for a question, I have one that is half-related maybe.
41:53
So I get asked a lot because I see a lot of kids with hypertension,
41:56
right? And so the question always is, does hypertension cause headaches?
42:00
And, you know, I always get mixed answers and opinions when you ask around.
42:04
But curious to know your thoughts on that question.
42:07
So I would say yes to that because PFOs, for example, PFOs are directly related.
42:13
So shunting, they say if you have a PFO, the patient will have an increased
42:17
risk of migraine, especially with aura.
42:19
But PFO management surgically doesn't really do that.
42:22
So yes, basically to answer your question, if there's decrease in blood flow,
42:26
certainly people with hypertension, if you've talked to them,
42:30
and I'm sure you have, they will have a lot more migraines.
42:33
If it's disturbing your vasculature, like in the slides, and it is decreasing
42:38
or causing any form of decreased blood flow cortical spreading depression,
42:41
I think it certainly can.
42:43
Hence, propanolol will work. And the theory behind how these medications,
42:48
how does propanolol not work, is because they decrease the excitability of the neurons.
42:54
So I think it's certainly a good question.
42:59
But yes, people with hypertension. We don't see a lot of children with hypertension,
43:03
except if they're coming from the nephrology clinic, but yes,
43:06
they are at risk for having more migraines. And they're easier to treat.
43:11
Candice Sartan, I think I share a patient with you already, right?
43:15
Yes, yes, the Candice Sartan patient, yeah.
43:17
Candice Sartan, so yeah, so I would say yes to that.
43:22
Thank you. We've got a question from Dr. Manalik. You can go ahead and unmute yourself.
43:27
Hi, thank you for the wonderful presentation. I'm an outpatient pediatrician in the GenPeds group.
43:33
So I have kind of more lifestyle-related questions.
43:37
I've seen kids where I wonder about the effect of screen time on their,
43:44
like as a headache trigger, but also making kids who wouldn't otherwise be prone
43:49
to headaches or migraines be at risk because of the amount of screen time that
43:54
they get, even if it's not sleep-related, right?
43:57
And then the other related thing I've wondered about is head pain.
44:02
Like sometimes patients will come in, usually like school age or teenage,
44:06
where they are complaining of head aches, but on palpation, they actually have tenderness.
44:11
And maybe it's because I'm a DO, but I think about the muscular strain because
44:16
of positioning, maybe because they're holding their screens in front of them
44:20
and they're hunched over.
44:22
So, I wondered if there's any data or evaluation on those things. Thank you.
44:28
Yeah, absolutely. I'll start with your second question, which is very interesting
44:31
because, yes, this, what you're talking about, this thinness,
44:35
that is called, the term they use for it is called allodynia.
44:39
Allodynia. And allodynia is a term and there are actually case reports on it.
44:44
Being a migraineur myself, I also
44:46
have allodynia. I can never tie my hair because when I tie them, I can't.
44:50
It just pulls on the scalp and there will be a migraine.
44:54
A lot of patients with migraineurs hair. So we are very sensitive.
44:57
Migraineurs are sensitive because they are sensitive to noise, light, sound.
45:01
And there's a term they use for it called central sensitization,
45:04
in which they are just hypervigilant.
45:05
They are. Okay. So there. So to answer that, the palpitation,
45:10
when you do that, that's allodynia.
45:13
So I don't know how frequent their headaches are, and do they need to be on
45:17
a daily preventative medication? I'm guessing yes.
45:19
So that was central sensitization or allodynia. First question,
45:23
yes. Screen time, I think AAP guidelines are like two hours a day maximum.
45:27
And if you actually listen to the people who are Apple, and if you listen to
45:33
them, I've listened to their talk.
45:34
They say, we don't let our children near these devices.
45:37
So these devices are addictive. They activate your limbic system.
45:40
It's this reward, quick reward, quick reward.
45:43
You know, I want it, I get it right now. And this is how I'm going to be now
45:47
for the rest of my life because I need it right now.
45:49
There's no, so it's messing with the children.
45:53
I'm extremely against it. So screen time shouldn't be more than an hour or two hours a day.
45:58
I mean, it's easy for me to say because I don't have any kids, but still.
46:02
But reward, this reward system, even when we see these reels on Facebook,
46:05
I think it's this quick reward system. It's very bad for us.
46:09
All right. There are a few questions in the chat.
46:13
The first one is, for the general pediatrician, do you have a preferred sequence
46:19
or order of medications you'd like to see them use, including over-the-counter
46:22
medications, vitamins,
46:24
lifestyle recommendations before they're referred to your clinic? Great. Good question.
46:29
Usually, I give them two months because this data has shown that it takes two
46:34
months for daily preventative medications to work.
46:36
So when I start with vitamin supplementation, like I said, the one that I like to use is Migrelief.
46:42
And then there's another one, Migrelief, I don't use so much all over the counter.
46:45
I usually like to give them at least two months of that.
46:49
But I like to do everything together because I won't say, okay,
46:51
let's give you a vitamin supplement for two months. Then you start losing weight
46:54
the next two months. So, you know, doing everything together.
46:57
And I speak more so also personally as a patient myself, because I think acupuncture
47:02
and these vitamin supplementation, lifestyle modification, at least should be
47:07
tried for two months or so.
47:09
You can do it all together. It wouldn't hurt, you know, and then if it's still
47:13
not working or if they have any focal neurological sign or if they are in medication
47:17
overuse, then that's that we just don't want to go there. We just do not want to go there.
47:21
Review the order of medications you would like to see.
47:25
Vitamin lifestyle modification. I think I would do this all like I wouldn't
47:28
wait weeks between them. I would probably do them together. You know what I mean?
47:34
The next question is, how often is, Dr. Gross, how often is syncope seen in migraine patients?
47:40
Dr. Gross, we see a lot of patients with migraines and we see a lot of patients with epilepsy also.
47:45
And, you know, syncope, I won't be able to tell you exactly the percentage,
47:50
but I can tell you that a lot of migraineurs are prone to syncope vertigo.
47:55
Now, could that be a part of your aura? Could it be a brainstem aura?
47:58
Difficult to say. Of course, we have to look at the literature very closely.
48:02
And there are slides that I have on it.
48:04
Are you meeting the criteria for migraine with aura? Yes or no?
48:07
There are slides on it. If they're not, if it's just syncope,
48:10
I have not seen it very frequently.
48:12
However, there's a term called dysautonomia or POTS, right?
48:16
So in those cases, the patients are prone to having headaches and they can have
48:20
syncope quite frequently.
48:22
We, again, the workup for syncope is, like you already know,
48:25
would include like the cardiac workup and, you know, the tilt test, et cetera.
48:29
But there's no medication I would give for syncope be other than,
48:32
again, lifestyle modification, adequate hydration, et cetera.
48:36
Why are we still prescribed to FMAX and amytriptyline if they're not better than placebo?
48:40
That was one study that showed that, but there are other studies.
48:43
So the CHAMP study was supposed to be, you know, I think I was, I was still a fellow.
48:47
I was a headache fellow at that time. No, I had just graduated in 2017. Yeah.
48:51
Two years out. So I remember it was like the big study that was coming out.
48:54
Everybody was excited about it, but it's, it's sad.
48:57
It could be several other factors too, but there are several other studies that
49:02
have shown amy triptoline to be effective. Topamax, quite effective.
49:06
We had a poster recently, actually, Dr.
49:09
Fox and I and my other colleagues at the University of Illinois,
49:12
and that showed no significant change. We compared amy triptoline to Topamax.
49:18
But again, having been treating migraines since 20, I think 15,
49:23
in children, I think Topamax is overall very well tolerated.
49:26
The other thing is it can cause a lot of weight loss too.
49:29
And weight loss and headache is directly, it will be great. So if it can cause
49:34
weight loss in a healthy enough way, that's also effective.
49:37
But amitriptyline overall can also help with mood and depression and sleep.
49:41
So if it's also helping with sleep and weight loss, but there are several other
49:45
studies that have looked at these medications.
49:48
So unfortunately, yes, the CHAMP study was quite a disappointment,
49:51
but it really, we brought it up.
49:55
I talked to Dr. Fox about it too, because it's important because it highlights
49:58
the importance of placebo and also multidisciplinary, multifactorial approach.
50:04
Medication overuse headaches, chronic daily headaches, NDPH.
50:06
NDPH is very hard to manage and success rate is not going to be high unless
50:11
and until we have a multifactorial approach, which includes everything we talked
50:16
about, not just one pill,
50:17
not just Topamax. That's where we fail.
50:21
We have a question hand-raised from Dr. Herndon. You want to unmute yourself, sir? Yeah.
50:27
So in the process of discovering new cancer drugs, we have a bunch of plant
50:33
biologists who've been involved with that kind of discovery work.
50:39
And it turns out, well, I have a sister-in-law who has horrible migraines,
50:45
and they seem to be aggravated or related to exposure to mold spores.
50:51
When the cows get really high they're allergic related and somebody in the community
50:56
knew about a plant that's called something like horse clover or something like that.
51:05
And they made a tea out of it and gave it to her and her headaches which might last for days,
51:14
just disappeared all of a sudden and it's the most dramatic thing i've ever
51:18
seen in a long time So I went to the plant biologist,
51:22
and it turns out that we had samples of that, and some people were looking at
51:27
it, but not for that as a chemotherapy agent.
51:32
And it had been, in folklore times, had been used for menstrual cramps.
51:39
So that led to the discussion, well, it's a prostaglandulin.
51:43
And i mean this is kind of a convoluted story
51:47
but there are people there are plant biologists in the pharmacy department here
51:53
in san antonio who have these catalogs of all kinds of things and i don't know
51:59
you know what these things are but it seems like an area of discovery to me,
52:05
sounds sounds amazing i am personally i'm a big believer in herbal medicine
52:10
i've used it on myself Of course, I can. I mean, yeah, but I've used it on myself.
52:16
I can talk about it for a long time, using turmeric and other stuff.
52:20
I use it. Can you tell me the name of the plant again? This is very interesting.
52:23
I think it's called horse clover or something like that. It's a very unusual plant.
52:30
It has a flower, and the stalk grows through the middle of the flower to the
52:35
next level, and there's a series of flowers.
52:38
And, of course, it gained its name because horses like to eat it.
52:43
Very interesting. I think that's kind of the theory behind Ayurvedic medicine.
52:47
And that's not something we, you know, but Ayurvedic medicine,
52:50
it's worked very, very, very well.
52:52
So I wonder if that's something I look it up for school work.
52:57
Thank you so much for listening to that fascinating talk. Don't forget to click
53:03
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53:06
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53:13
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53:17
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53:22
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53:34
That's Pediatrics Now for Parents, wherever you get your podcasts,
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53:41
I'm Holly Wayment, and I'll see you soon.