The Neurotransmitters: Clinical Neurology Education

IM Board Prep #1: Headache

January 11, 2024 Michael Kentris Episode 30
The Neurotransmitters: Clinical Neurology Education
IM Board Prep #1: Headache
Show Notes Transcript Chapter Markers

Hello and welcome to our new mini series designed to help prepare internal medicine residents get ready for the neurology section of their board exams! 

While it is aimed at IM residents it is a good review for anyone feeling a little rusty on headache. 

In our first session we talk about diagnosing different headache disorders, red flag symptoms, and some treatment considerations for the more commonly tested disorders. 

After listening to the episode give our quiz a try (link below)!
https://forms.gle/G2QQisD55wtNXEhE6

Learn more about headaches from the International Classification of Headache Disorders website: https://ichd-3.org/

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The views expressed do not necessarily represent those of any associated organizations. The information in this podcast is for educational and informational purposes only and does not represent specific medical/health advice. Please consult with an appropriate health care professional for any medical/health advice.

Michael Kentris:

Hello, dear listener, and welcome back to the Neurotransmitters. I'm very happy to announce that we are starting a new mini-series within the podcast covering the spectrum of clinical neurology, with a focus on board review and preparation aimed primarily at internal medicine residents. This means there will be a little bit more of a focus "buzzwords buzzwords that may show up on tests and question stems and a little bit less of the nitty-gritty details than what we sometimes get into on the show. I will also be including a link to a short quiz online in the show notes for those who want to get the full learning experience. So today we are starting with a very ubiquitous topic, both in neurology and in medicine at large, and that is headache. What we'll be reviewing are families of headache disorders, the essential elements in the history when evaluating a headache and treatments for various headache disorders, with a bit more of a focus on migraine-related treatments. Headache can sometimes be a challenging disorder to evaluate, and why is that? Well, if you don't take the time to ask the questions from the patient, then you're going to be missing out on a lot of essential information, because very often, especially with our primary headache disorders, which we'll get to in a moment, the physical examination may be fairly unrevealing. When thinking about headache, I think it's useful to have a framework to start with, and the International Headache Society does have just such a framework called the International Classification of Headache Disorders version 3, or the ICHD3, and they group them into three big families primary headaches, secondary headaches and cranial neuralgias. So let's start by just taking a little peek into what is in each of these big categories. Primary headaches include probably our most common headache disorders, including migraine, tension-type headaches and trigeminal autonomic cephalalgias. The most common example that people are familiar with is likely cluster headache, and we'll talk about some other things in that particular subclass as well as we go forward. Secondary headaches, as the name suggests, are headaches which are secondary to another issue, and these include a whole wide swath of problems including trauma, cranial or cervical vascular disorders, intracranial disorders, substance abuse, substance withdrawal, infections, so on and so forth. Essentially, if there is another medical issue ongoing or a precipitating event leading to the headache, it is generally considered a secondary headache. And in the third category are neuropathies and facial pains and other headaches. The quote unquote "other headache disorder, and the most common example of this would be something like trigeminal neuralgia, and we'll talk about some other neuralges that can also occur and are important to recognize in clinical practice.

Michael Kentris:

So let's talk about the history in headache. I think there are two nice ways to frame this. There is the temporal profile and then there is the symptom profile and so using these two things together, we're able to create ourselves a nice differential diagnosis. So in the temporal profile again, some of this will be a little basic. But the onset, when did it start, and how long have the headaches been going on at their present rate? Sometimes you need to dig into that a little bit.

Michael Kentris:

Just as important, you need to evaluate the frequency of the headache. So how many headache days are they having over an average the last three months? Sometimes they're not able to give you that, so you need to shorten the duration, maybe to a month, a week, and then kind of extrapolate out from there and guide the patient in the history a little bit. But that is important in terms of deciding how disabling the headaches are and whether preventive medications or other things like that are appropriate. Associated with the total frequency is the frequency of severe headache days, and these are often defined as days where the patient's ability to work, engage with social events, has had to change their plans have been affected by the severity of the headache. If someone's got to stay at home in a cold, dark room with a pillow over their head and blackout mask on that's, that is a disabling headache. Sometimes, if they're not able to tell you how many headache days they are having, you can ask them how many days did you have no headache whatsoever? And if their headaches are chronic enough and severe enough, that pain-free day will be more noticeable against the background of the chronic pain. There are some different assessment tools that people will use in their charts to document progression over time and try and be a little more objective. One of the ones that's a little more common or popular is MIDAS, the Migraine Disability Assessment Scale, and that helps kind of create a numerical value to some of these things we're just talking about.

Michael Kentris:

Another piece of information that is useful is how many days is the person needing to take medication for their headaches, and very often you'll have to ask specifically about over-the-counter things. A lot of times people don't consider over-the-counter meds to be quote unquote medication, and so they won't tell you about taking Acetaminopteracetamol for our overseas friends aspirin, etc. So you do need to be very specific about taking anything, whether that is prescription or over-the-counter, and, as an addendum to that, were those medications actually helpful? Because one thing you will find is that people with chronic headache will frequently use these medications to an excessive amount, which, in addition to liver and kidney injury, can also lead to medication overuse headache One of our secondary headache type disorders that we'll talk about more later. The final piece of our temporal profile in terms of the history is the duration of the headache day itself, anywhere from minutes, hours up to several days for some people, and this you want to find out if it is treated. Did they take something over the counter prescription? Or how long does it last if they don't take anything? And both of these pieces of information are helpful. It may tell you whether the medication is working, whether the medication is working, whether they're having side effects or if the medication is just not working at all.

Michael Kentris:

Now diving into the other half of our history for headache, the symptom profile, and there's a few things here that are going to sound very familiar to anyone who's been through medical school. So first is the pain itself, the location of it. Where on the head or neck is the pain most? How does it spread, what is the quality of it or the character I sometimes say. What is the flavor of this pain Sharp, stabbing, dull, throbbing, pounding, etc. And what is the severity? A lot of people will use the scale of 0 to 10, with 10 being the most severe pain that someone could imagine, which can be helpful for tracking people's response to treatments and other interventions over time. You also want to ask how routine physical activity, such as going up and down a flight of stairs or other things of a similar level of exertion, may affect the person's pain, as migraine specifically tends to get worse with routine physical activity.

Michael Kentris:

Next, we want to dive in a little bit to the associated features. Right, so there's the headache itself, but for many people there is often a prodrome. People may feel a little rundown, kind of flu-like, anxious, trouble concentrating, various other kind of neurocognitive types of side effects, and so those can sometimes, especially with migraine, be something to ask about in the time leading up to the headache itself. Are there any associated sensitivities to light, sound, smells? Do they have nausea or vomiting either preceding or during the events? Any other neurologic complaints, numbness, weakness, especially visual auras? Right, we'll talk about those more when we get into migraines. And then is there a presence of any cranial autonomic features, and again these kind of go with our trigeminal autonomic cephalalges primarily, and these include classically tearing of the eye, congestion or sinus congestion, rhinorrhea, ptosis, injection of the conjunctiva, usually on that same side of the face as the headache, and we'll talk about these particular symptoms more when we get into that family of headache disorders.

Michael Kentris:

Also, other factors that we really want to investigate in our history is is there a family history of headache, particularly migraine, as it does tend to run in families? We want to get a detailed medication history right. Headache is a very common side effect for a lot of medications, so you really want to dive into whether there was any temporal association between starting that medication and the onset of the headaches. And while we talk about medications as thinking prescription, but you need to ask specifically about over the counter medications as well as supplements, vitamins etc. Etc. So anything new that may have been introduced around the time of the onset of the headaches Now, something that is unlikely to show up on the exams but in real life, I think is still an important thing to ask about are the general habits of the person, and we're talking about things like quality of sleep, anxiety, depression, as well as caffeine use and things like that that may also be triggering events. So general health and wellness are very important. So lifestyle counseling and evaluation is always an essential part of any proper real world headache evaluation as well.

Michael Kentris:

The last part of our history is the part that may be the most familiar to those with a medical background, and this is the part that very often on the test will be important and it is important in real life as well. And these are the questions that suggest different provocative features or triggers that make us concerned about secondary headaches. There is a nice acronym for this, the SNOOP4, or an extended version called the SNOOP 10. And this is an acronym that kind of gives us some different signs and symptoms to watch out for that make us concerned about secondary headaches. So S systemic symptoms. This includes things like fever, elevated blood pressure, a history of cancer or metastatic disease, other things like that. N is for neurologic signs or symptoms, and also N is for neoplasm.

Michael Kentris:

O onset - sudden. This is our thunder clap headache, maximal headache intensity in less than 10 seconds. Traditionally, O is onset after age 50, right, so most of our primary headache disorders are going to be in people younger than age 50. If we have a new headache after that we have to start thinking about other causes. P is for pattern change and there's a lot of other P's under this pattern change.

Michael Kentris:

This includes progressive worsening or change in nature or the character precipitated by cough, val salva or sneezing, anything that can transiently increase the intracranial pressure so that bearing down movement, postural changes worsen, and this can be high or low CSF pressure. Right. So if you're standing up, you have a low CSF pressure. That can worsen your headache. If you have high CSF pressure, like someone with idiopathic intracranial hypertension or pseudo tumor cerebri, then the headache is often worse with lying down, having papilledema on examination, which obviously requires us to do a fundoscopic examination. So bust out those fundoscopes and make sure to look in people's eyes if you're evaluating them for headache. Very important. Another P if they have new onset headaches in the pregnancy or postpartum period. Women who are pregnant or in the postpartum period are at higher risk for a few things like cerebral venous thrombosis, pituitary apoplexy. So any new headache in this particular time period should be viewed with suspicion. Our final P is painful eye with autonomic features and this can suggest pituitary issues, ophthalmic issues, cavernous sinus thrombosis and, without the autonomic features, we can also consider things like optic neuritis.

Michael Kentris:

So now that we have our history questions down, let's move into the first of our categories, and these are the primary headache disorders, and we're going to talk about a few of these specifically. So let's start with migraine. So migraine is a great mimic of many other disorders and that's because the auras that can come along with it can be so variable. So first of all, migraine can occur with and without aura. So let's take a look at the ICHD three criteria. So I'm going to read these out for you here. So first we want at least five attacks fulfilling our subsequent criteria. These criteria include a headache attack lasting 4 to 72 hours, untreated or unsuccessfully treated.

Michael Kentris:

A headache has to have at least two of the following four characteristics" Unilateral location. Pulsating quality. Moderate or severe pain intensity. Aggravation by or causing avoidance of routine physical activity, such as walking or climbing stairs. During the headache, at least one of the following nausea and or vomiting. Photophobia and phonophobia not better accounted for by another ICHD3 diagnosis. I always get DSM vibes from this one, just because it is one of these things where, if the headache is occurring, it temporarily associated with some other thing, then it is related to that other thing. So, for instance, someone with a traumatic brain injury or concussion develops headache, then it is attributed to that injury. So those are our migraine without aura.

Michael Kentris:

But what about migraine with aura? Now we keep saying aura. What do we mean by aura? So these are fully reversible visual, sensory and or speech or language symptoms, and these specifically carve out motor, brainstem and retinal symptoms, and we'll talk about those as we go through those specific migraine disorders. So next we have this thing called a migraine with brainstem aura, and so these are called brainstem symptoms because they essentially localize traditionally to the brainstem, and these include at least two of the following fully reversible brainstem symptoms dysarthria, vertigo, tinnitus, hypoacusis, dyplopia, ataxia not attributable to a sensory deficit, decreased level of consciousness defined here as a GCS less than or equal to 13,. And no motor or retinal symptoms. Right Again, we have this carve out for these other migranous disorders.

Michael Kentris:

Next up is hemiplegic migraine, which includes fully reversible motor weakness, and it can also have fully reversible visual, sensory and or speech or language symptoms, just like migraine with aura. But the tricky part is that the motor symptoms generally last less than 72 hours. But, as per the ICHD three guidelines, motor weakness may persist in some people for weeks. And this can be very challenging, especially if there isn't a proper history of recurrent stereotyped events where you can definitively make that diagnosis. So for both brainstem aura and hemiplegic migraine, you are very often working these patients out for things like stroke or other neurologic disorders if there is not a clear cut history of these reversible types of deficits in the past where someone has said, oh, you have this type of migranous disorder.

Michael Kentris:

And the last migranous disorder I'm going to be talking about in the recording today is retinal migraine. This is characterized by fully reversible, monocular, positive and or negative visual phenomena. And so these are your classic like scintillating skatomas, blindness, like the flashing lights, dark spots, all that kind of stuff confirmed during attack by either or both of the following a clinical visual field examination or a patient's drawing of a monocular field defect. Additionally, it tends to spread gradually over five minutes or longer. Symptoms last up to an hour and it should be accompanied or followed within an hour by a headache. Now you may be asking yourself how is a retinal migraine different from a traditional migraine with visual aura? The emphasis is generally being placed on its monocular character as opposed to being binocular like the traditional visual aura in a migraine. This is not an exhaustive list of migranous disorders, but for those who are interested in digging deeper, do check out the ICHD3 website, which I will include again in the show notes.

Michael Kentris:

Next up, we have tension type headaches. This is a headache typically bilateral, with a pressing or tightening quality of mild to moderate intensity, lasting minutes to days. The pain, unlike migraine, does not worsen with routine physical activity and is not associated with nausea, although photophobia or phonophobia may be present, and this can last anywhere from about a half hour up to a week. These are generally characterized as either infrequent at least 10 episodes of headache occurring on less than one day per month, on average less than 12 days per year. Or frequent at least 10 episodes of headache occurring on one to 14 days per month, on average for more than three months. And lastly, chronic headache occurring on more than or equal to 15 days per month, on average for more than three months.

Michael Kentris:

Next up, you have the trigeminal autonomic cephalalgia. I had one attendant who told me that many of these disorders are essentially change the symptoms into Greek or Latin, and that's just what it is so trigeminal nerve autonomic symptoms, cephalalgia, that is to say, your head hurts. So the common clinical features here are a typically unilateral headache, and they often have prominent cranial, parasympathetic, autonomic features, usually lateralized and ipsilateral to the side of the headache. These include, as mentioned earlier, conjunctival injection or tearing slash, lacrimation, nasal congestion or stuffiness or runny nose slash, rhinorrhea, eyelid edema, forehead and facial sweating, and then meiosis and ortosis. So the poster child for this family is cluster headache. I think everyone learns about this one in medical school. So these are attacks of severe, strictly unilateral pain which is orbital, super orbital, temporal or in any combination of these sites. These episodes usually last anywhere from 15 to 180 minutes, occur from once every other day to eight times a day, and the pain is associated with those same autonomic symptoms that we just mentioned. As well as this restlessness or agitation, as opposed to migraine, where people usually want to lie down and go to sleep, people with cluster headaches are often very agitated and unable to sit still. A quick note the pain is often incredibly intense and this is sometimes called the quote suicide headache because it can be so severe for some people.

Michael Kentris:

I do want to spend a little bit of time talking about the other, lesser known headache disorders in this family. These include paroxysmal hemi crania, hemi crania continua and short lasting, unilateral neural deform headache attacks, with some subtypes there For paroxysmal hemi crania and hemi crania continua. These are obviously very unilateral headaches and one of their unique features in addition to all of the autonomic symptoms, as we've mentioned before is that they tend to respond very significantly to endomethacin. So that can sometimes be a differentiating feature for this particular headache disorder as opposed to other things which may look similar. Under the umbrella of short lasting, unilateral neural deform headache attacks, we have two different entities. It is sunk and suna, which are both acronyms we'll get to in a second. So these are characterized. The criteria here are at least 20 attacks fulfilling these criteria, moderate or severe unilateral head pain with orbital, super orbital, temporal and or other trigeminal distribution lasting for 1 to 600 seconds.

Michael Kentris:

Very brief and occurring as single stabs, series of stabs or in a sawtooth pattern that sounds particularly unpleasant and at least one of the following five perennial autonomic symptoms or signs. It's a lateral to the pain and these are the same ones we've been mentioning conjunctival injection or lacrimation, nasal congestion or rhinorrhea, eyelid edema, forehead and facial sweating. Forehead and facial flushing, sensation of fullness in the ear and that's a new one meiosis and or ptosis. They occur with a frequency of at least once per day and they are not better accounted for by another ICHD3 diagnosis. So we mentioned these two acronyms sunk and SUNA. SUNCT stands for short lasting, unilateral neuralgiform headache attacks with conjunctival injection and tearing. SUNA stands for short lasting, unilateral neuralgiform headache attacks with cranial autonomic symptoms. That's the A there, and it has only one or neither of conjunctival injection and lacrimation.

Michael Kentris:

Moving on, we have our next category, which are painful lesions of the cranial nerves and other facial pain. Again, we have some prototypical disorders. The first on the docket here is trigeminal neuralgia, and this is characterized by recurrent attacks of unilateral facial pain in the distribution of one or more divisions of the trigeminal nerve, with no radiation beyond, and it has the following characteristics the pain is typically lasting from a fraction of a second up to two minutes, it is severe in intensity and it has an electric shock like shooting, stabbing or sharp quality. This can sometimes be precipitated by innocuous stimulation within the affected trigeminal distribution and again, it should not be better accounted for by another diagnosis. Now you may be asking yourself how does trigeminal neurology differ from our SUNCT/SUNA and paroxysmal hemicrania, and that is a good question, because they can clinically look very similar to one another. Now, classically, trigeminal neurology usually has a refractory period after each attack, but there can be some overlap with our short lasting unilateral neuralgia form disorders. Additionally, we would expect the autonomic symptoms to be more prominent, with the trigeminal autonomic cephalalages rather than the trigeminal neuralgia, and while this is usually the case on any tests or exams that you encounter in real life, things may get a little fuzzier.

Michael Kentris:

Now for trigeminal neuralgia. They characterize it as three subtypes. There is classic, secondary and idiopathic. So classic trigeminal neuralgia is often due to neurovascular compression of the nerve root, which opens up the possibility of surgical decompression as a treatment modality for these specific patients. Secondary trigeminal neuralgia, as you may have guessed from the name, is usually secondary to another disorder, and one of the more common ones would be something like multiple sclerosis. So, for instance, you may receive a clinical vignette where someone develops bilateral trigeminal neuralgia and that is very suspicious for something like multiple sclerosis or some other kind of pathologic process in the brainstem. And, of course, lastly, is idiopathic, which usually means that your imaging is all unremarkable and there is no compression. There is no pathologic process going on in the brainstem or along any of the nerve as it travels along its way.

Michael Kentris:

Similar to trigeminal neuralgia, you can also have glasopharyngeal neuralgia, which typically causes pain in the ear, base of the tongue, tonsillar fossa or around the angle of the jaw, sometimes provoked by swallowing, talking, coughing, etc. Another common neuralgia to be on the lookout for is occipital neuralgia, typically associated with shooting or stabbing pain in the posterior part of the scalp. It can be on one side or both sides and very often it is affecting the greater, lesser and or third occipital nerves. It's important to recognize these patients as they can have pretty good response to a nerve block in the area of the affected nerves which can be pretty life changing for some people affected by this.

Michael Kentris:

There are many other headache disorders out there, too many for us to cover in this podcast, but I did want to do some quick hits on some other unusual primary headache disorders. So there is a primary cough headache, pretty self-explanatory, I would think. Similarly, primary exercise headache, primary headache associated with sexual activity. This can be what they used to call pre-orgasmic or orgasmic. There is a primary thunderclap headache which can be very concerning because it can mimic subarachnoid hemorrhage and other things in that neurovascular family. There is a cold stimulus headache, that is to say, a brain freeze, the external pressure headache if your head's being pressed on, it can cause a headache Primary stabbing headache, particularly unpleasant, a numbular headache or a coin-shaped area of pain, and then a hypnoketic. This can be a little strange, also because people will often wake up from sleep with a headache, which is a little bit unusual for many types of headaches.

Michael Kentris:

Now let's move on to talking about different treatment options. So there's two camps. There's essentially the rescue or abortive medication, and then there is the preventive medication. Most of the time, the approach is going to have to be tailored to the individual, and that's going to be looking at what are the side effects of each medication as well as what are the other coexisting medical problems that the patient has, and that's how a lot of these question stems are written to trip you up specifically and, to be honest, that does happen in real life as well. So it is good to know about the side effects and the potential complications of the medications that we are using.

Michael Kentris:

So we're going to start off with migraines specifically, just because they tend to show up most often on the exams and they are very common in real life also. So if you do have someone who has not tried any over the counter medications and they have mild to moderate symptoms, it is very reasonable to start with non-steroidal anti-inflammatory drugs, or NSAIDs, and this includes things like aspirin, diclofenac, ibuprofen, naproxen. These all have level A evidence for acute treatment of migraine and they're very reasonable to use first line treatments. Now, obviously, NSAIDs have GI risks, including ulcers and bleeding, as well as cardiovascular events, so you do need to watch to make sure these are not being overused and, as we mentioned earlier also, this can, if they're being used for more than 15 days per month, lead to a medication overuse headache. This is one of our secondary headaches related to medications, and this can occur as a sequelae of overusing these rescue medications from any of these families NSAIDs, triptans, etc. And so it is something that we have to be aware of in terms of how often is someone needing to use the rescue medication, and if they are overusing this, it can paradoxically make the headache worse.

Michael Kentris:

One of our other big families that are used for migraines are triptans. These are basically serotonergic type medications and they are indicated for acute migraine treatment. Now you do have to watch out because there is some vasoconstriction associated with these. So relative contraindications include things like a history of stroke or coronary artery disease, although this is somewhat debated. There are a plethora of triptans out there sumatriptan, rizatriptan, zolmotriptan, etc. And these have different half-lives, different modes of administration. Some of them are available subcutaneously, via nasal spray, etc. So you do need to look and see how fast those patient symptoms come on. How quickly do they need the medication? Maybe they have excessive nausea and or vomiting that would preclude them from taking an oral tablet. So those are all considerations when selecting a medication.

Michael Kentris:

As far as the triptan family, very similar to triptans are the ergots or DHE, specifically dihydroergotamine. While it is pretty similar to triptans in its effect, it has a bit broader activity and so sometimes is used in folks who don't respond to triptans. Initially. I do want to mention the gepants or the CGRP blockers. There are some options now in the rescue family, ubrogepant, specifically, which has been shown to be fairly effective. I don't know if this is showing up on tests yet, but it may in the next year or two. But it is also an option for people for rescue therapy.

Michael Kentris:

Lastly, a pet peeve and also a recommendation. Opioids and butalbital containing products think things like Fioricet are not recommended typically in migraine. They are not recommended as first line, nor are they recommended to be prescribed for long periods of time. So they all have their own problems and likely do more harm than good in the majority of cases. So for migraine specifically, try to avoid these. Lastly, if the patient does have significant nausea or vomiting, it is good to have some sort of anti-emetic therapy on board. Ondansetron typically is less effective compared to a lot of the other options like promethazine or prochlorperazine.

Michael Kentris:

Moving on to preventive migraine treatment, the first question you may ask yourself is when is the right time to discuss that with someone? When is the right time to recommend someone start preventive medication? Some of the criteria that are used are people who have too severe or disabling or for less disabling migraine attacks per month. So similar when we were talking about the history earlier in the podcast. People who can't go to work, who can't go out with friends or family, who can't do work around the home. These types of things would be considered generally more or less disabling. We would also consider preventive treatment for people for whom acute migraine treatments have not been effective or they are contraindicated for some reason. We would consider for people who have medication over use headache, for people whose migraines, though maybe rare, are highly disabling. These would be like our people with hemiplegic migraine or the migraine with brainstem aura patients. And lastly, it's fine if the patient just prefers to be on a preventive medication. There's nothing wrong with that.

Michael Kentris:

So when we're looking at the different families of medications used for preventive therapy for migraines, we kind of fall into a few buckets. We have our antidepressants, we have our antihypertensive medications and then we have our anti-seizure medications and then there's a kind of smattering of other things that don't fall nice and neat into one category together. So, starting with the antidepressants, we have two main classes. There's a tricyclic antidepressants and there are the serotonin nor epinephrine reuptake inhibitors or SNRIs. There are multiple different TCAs. However, the two most common ones that we use for headache are amitriptyline and nortriptyline. Nortriptyline tends to be a little more effective, a little more helpful with sleep because it is a little more sedating. It has a little more anti-cholinergic side effect, which can be a plus if you're using it for sleep, but can also have some negative side effects in as much as more weight gain, dry mouth, dry eyes, constipation, etc. As opposed to nortriptyline. So selection does depend a bit on tolerability and the patient whether or not they have side effects. One other key aspect to be aware of is that while TCAs and SNRIs can both be helpful for neuropathy, people with restless leg syndrome specifically may have exacerbation of those symptoms on TCAs. So if they have a prior diagnosis of RLS you may want to avoid those medications. The main two SNRIs that we talk about for migraine prevention are venlafaxine and duloxetine. Venlafaxine may have a bit more evidence behind it, but it may cause a bit more withdrawal when it is discontinued. People who might receive some extra benefit from SNRIs as their migraine prevention medication include those who already have a neuropathy from some other cause or, for duloxetine specifically, people who may have fibromyalgia also. Next up we have our antihypertensive medications for migraine prevention.

Michael Kentris:

I think everyone is fairly familiar with propranolol as an option for migraine prevention. It is a nonselective beta blocker, which means that whenever you see in a question stem someone with a history of asthma, you generally want to not pick that choice. So the history of asthma is definitely something to keep in mind, as well as whether or not they tell you about any low heart rate. In the vignette. Less frequently used, but still options to consider in real life, are metoprolol and timolol, which can both be used for migraine prevention but aren't used as often as propranolol. Verapamil, a calcium channel blocker, is also an option, and it's particularly used in folks who might have particularly bad auras, such as brainstem or hemiplegic. There is even evidence to support the use of lisinopril and candesartan, an ACE inhibitor and ARB respectively. Unsurprisingly, the main contraindication for medications from the antihypertensive class is going to be hypotension. You should also avoid them in anyone planning to become pregnant.

Michael Kentris:

Next up are anti-seizure medications. There are several potential options within this family, but the two most commonly used are topiramate and Valproate. While both of these can be quite effective for migraine control, they also have a number of potential side effects that it's important to be aware of. So topiramate may be a good selection for someone who has issues with being overweight or obese, as it does have some appetite suppression effect and is in fact, even used in some combination medications for weight loss. But it is not all sunshine and roses for topiramate. It is sometimes also called Dopamax, a riff on its brand name of Topamax, as it can cause some pretty significant cognitive issues, all the way from some mild word finding difficulties up to more significant memory issues in some people. Other potential issues to be aware of with topiramate include some paresthesias around the face and fingers, as well as an increased risk for kidney stones. So people do need to stay well hydrated, and having a history of kidney stones is a relative contraindication to using topiramate in those specific people.

Michael Kentris:

You don't see Valproate used specifically for migraine nearly as much as in years past, and this is because it just has such a laundry list of potential side effects. These include things like sedation, weight gain, hair loss, getting hair where you shouldn't, liver issues, liver toxicity, specifically thrombocytopenia, and both topiramate and Valproate are teratogenic and Valproate specifically should be avoided in any women of childbearing age. As always, constantly your patients about potential risks of medications, particularly when it relates to pregnancy, is very important. Other anti-seizure medications that are sometimes used as preventive agents for migraine include gabapentin, pregabalin, zonisamide, which zonisamide is somewhat similar to topiramate and may be an option for those people who maybe got some benefit from topiramate but really couldn't tolerate the side effects very well. The last class of medications I want to talk about for migraine specifically are the calcitonin gene-related peptide monoclonal antibodies or the CGRPs. These are usually once monthly injections, like erenumab or galcanezumab, and their side effects typically include injection site reaction, hypersensitivity and constipation, sometimes severe constipation. So those are the main things to watch out for with this family of medications. I don't know if these are showing up on questions for IM boards yet, but if they aren't yet, they probably will be in the next couple of years, I would imagine.

Michael Kentris:

Moving on from migraine, let's talk a little bit about the trigeminal autonomic cephalalgias. I think everyone knows from medical school that clustering headaches first line is oxygen therapy. However, insurance is a real bear about getting this approved, so sometimes that isn't really feasible. Triptans are another option, including subcutaneous or nasal spray. Verapamil and valproate have both been used as preventive agents and galcanezumab has been approved also as a potential option. And we'll finish up today by talking a little bit about the treatment for trigeminal neuralgia.

Michael Kentris:

So medical therapy typically begins with carbamazepine, and carbamazepine, as most people will know, is a sodium channel blocker. It is also a CYP450 inducer, a very strong inducer, so you do have to watch out for medication interactions. Carbamazepine will also auto-induce its own metabolism after you start it in the first few weeks, so you do have to be cognizant of that also. Carbamazepine belongs to the sodium channel blocker family of anti-seizure medications and the side effect profile that is pretty ubiquitous. Among sodium channel blockers, to one extent or another, are the three D's Dizzy, drowsy, drunk, so Dizziness, sedation and Ataxia. So you do have to watch out. These are usually dose dependent side effects, but they can be very common, depending on how well the person tolerates it and whether there are other medications on board that can compound that effect.

Michael Kentris:

If someone is intolerant carbamazepine, oxcarbazepine is also an option. Oxcarbazepine very closely related to carbamazepine. It has a slightly better drug interaction profile and doesn't have quite as many side effects as carbamazepine does itself. However, it may predispose slightly more towards hyponatremia, so you do need to keep an eye out for that, as that risk for hyponatremia does increase with increasing age.

Michael Kentris:

Other medication options that are often tried do fall into similar lines as far as belonging to the anti-seizure medication class, and most of them to the sodium channel anti-seizure medication, specifically things like eslicarbazepine, phenytoin, lamotrigine, and there are others that can be tried as well, like Gabapentin, baclofen, valproate topiramate, levetiracetam, etc. For an acute rescue medication, option IV fosphenytoin is sometimes used as well If medication therapy produces intolerable side effects or is otherwise ineffective. There are surgical options including, like we mentioned earlier, microvascular decompression if there is evidence of a vascular loop, or stereotactic radiosurgery, partial sensory rhizotomies other types of lesioning of the trigeminal nerve. If you've made it this far, thank you so much for listening and coming along with us on this journey through headache treatments and diagnosis, and if you want to test your metal a little further, there will be a link to a small quiz you can check your knowledge, make sure this stuff is sticking and put it into practice as soon as possible.

Michael Kentris:

For people who are listening, who are part of the internal medicine class where I'll be teaching, we'll be going through these questions live, together with in-person explanations, and for those who are listening to this later online, if that's something that you would like to see or participate in, drop us a line, send us an email contact at theneurotransmitterscom and please let us know if you're getting something out of this, if you think this is useful. If you want us to keep posting this stuff to the podcast feed, I hope it is and please let me know. I very much appreciate hearing from each and every one of you guys. If you want to find more neurology education content online. You can find us at theneurotransmitterscom. You can find me online on X, formerly known as Twitter, at DR Kentris. That's K-E-N-T-R-I-S or the Neurotransmitters account at Neuro underscore podcast. Thank you all for listening and we will see you again really soon.

Introduction to IM Board Prep series
Categories of Headache Disorders
Headache history
SNOOP 4/10 for secondary headaches
Migraine
Tension Type Headaches
Trigeminal Autonomic Cephalalgias
Treatment Options