One in 26 people will develop epilepsy in their lifetime, but many conditions – in addition to epilepsy – can trigger or look like a seizure. To help PCPs make efficient initial evaluations, neurologist Manu Hegde, MD, PhD, breaks seizures into basic classes and puts the numerous epilepsy syndromes into three useful categories. He discusses how to take better histories; what to check for during physical exams; and what to know about antiseizure drugs, including specific side effects.
Well, thank you very much. I really appreciate the invitation and uh it's an honor to speak with um primary care colleagues um who are, you know, really the backbone of medicine. So thank you for your time. Um, I, uh, I wanna try and make this talk as useful for you as possible. Um, we'll, we'll talk a little bit about what a seizure is and how it relates to the diagnosis of epilepsy. The differential diagnosis and approach to a first-time seizure, um, identifying the most common epilepsy syndromes, just so you, uh, know what the terminology means and, and, um, what those diagnoses, uh, are, are like. We'll talk a little bit about the risks and benefits of the most common anti-seizure medications. There's a myriad of medications, so we won't go through all of them, just, just the ones that I think might be most relevant to you. And uh talk a little bit about when to refer to specialty care and what we offer. So, first of all, definitions. Um, uh, a seizure, uh, is a paroxysmal stereotyped event that can include altered, uh, movement, sensation, experience, or consciousness, and it results from excessive brain electrical activity. We usually say that the hallmarks of that are, are hyper, hypersynchronous brain activity. Um, it arises from the cerebral cortex. You do not get seizures coming from deeper structures like the basal ganglia, the cerebellum or spinal cord. Um, and epilepsy is just defined as a disorder in which someone has recurrent unprovoked seizures. Usually, we diagnose epilepsy after someone has had two unprovoked seizures. Although you can be diagnosed with epilepsy after a single seizure if you have characteristic risk factors on your workup that are identified. Um, epilepsy is the 4th most common neurological disorder, um, and it affects approximately 1% of the population. 1 in 26 people will develop epilepsy in their lifetime. Um, and the etiologies, uh, you know, we could go on and on with, with the list, but all sorts of insults to the brain, um, or, uh, developmental problems with the brain can result in epilepsy, and those can sometimes cause other disabilities, um, but oftentimes, seizures are really the only manifestation of whatever that underlying cause is. Uh, epilepsy causes significant mortality, and I think this is not well appreciated. Uh, more people die from seizure-related incidents than, uh, uh, die from breast cancer. Um, and, um, those with uncontrolled seizures have an 8 times greater risk of premature death. So it is something to be taken seriously and to be aware of. Um, one problem with our field is that Every 5 years or so, a group of epilepsy specialists, which sadly never includes me, has some conference in the Mediterranean and they changed the names of all the seizures. Um, and, uh, so what used to be, uh, Petite Mall became complex partial, became, uh, focal. Um, and so now the terminology that we're using is, um, uh, is listed here, um, by the International League Against Epilepsy latest Classification. Um, the, the things that you really need to know though, I think are in yellow here. Seizures can be either focal onset or generalized onset, meaning how they appear to arise, uh, within the brain on an EEG. And within focal-onset seizures, they can be with preserved awareness or impaired awareness. We used to call this simple and complex partial, but focal-aware or focal unaware seizures. And then the process of a seizure spreading and causing a tonic-clonic seizure or a convulsion or a generalized seizure, we call those focal to bilateral tonic-clonic seizures. And then the other type of seizure or, or type of epilepsy really are generalized epilepsies in which the seizure seems to start all over the brain at once when you look at an EEG. So these are the two major categories, focal or generalized. Um, and it's important to know the difference because the medications and the treatments that we use are different. How do we make a diagnosis? Well, we take a good history as we do with, with any condition. We try to identify risk factors and get more information about the seizure semiology, meaning what did the seizure look like, what were the behaviors involved in the seizure. Um, we usually try to get an MRI, which is a structural test, and an EEG, which is a functional test. And so what's the differential diagnosis when someone has a seizure? Well, as you can imagine and as you probably know, that's a huge list of paroxysmal events, right? And um it will differ based on the characteristic of the event itself and the nature of the patient, the, the, the demographic that they're in. Um, and I think going through this entire differential is, is probably beyond our scope, but there are a few diagnoses that I think we should focus on because they are often, um, confused with seizures and, um, these are often relevant to folks in primary care. Um, we should also talk about medications because there are medications that can provoke seizures or trigger seizures. Seizure, uh, medications that can lower the seizure threshold. Um, this is not an exhaustive list by any means. The, the actual, um, exhaustive list is, is huge, but, um, if you look at Some of the most common medicines and, and those that are most strongly associated with seizures, this would be it. Analgesics, um, mainly tramadol is the, the medication that we watch out for. There are a number of, um, antimicrobials, antibiotics, um, that can potentially cause seizures as you've probably run into in your own practice. Tacrolimus is an immunosuppressant that can often result in neurotoxicity manifesting as seizures. There are psychiatric medications, um, the most, um, uh, um, concerning of which are Clozaril and bupropion, which can both, um, provoke seizures in people who have never had them before. Interferon alpha can do this. And then illicit drugs, um, cocaine, methamphetamine, alcohol withdrawal. All, these are all, um, uh, drugs of abuse that can cause seizures and in some cases, in someone with underlying epilepsy or at least a tendency um towards epilepsy, um, alcohol itself rather than the withdrawal can sometimes cause seizures. So let's talk about that differential diagnosis and, and um we'll do it with a case. I've got a few cases to talk about with you today. First case, 21 year old, previously healthy man goes to donate blood. He enters the facility, sees other people with IV lines, and reports seeing black spots and feeling nauseous. He appears kind of sweaty and pale to the, those in the room. He loses consciousness, he slumps to the floor. While on the ground though, he's noted to exhibit jerking movements of all extremities for less than 10 seconds. But then he recovers to baseline immediately after and is fully oriented with no neurological deficits. What's the likely diagnosis? And I'll let you think about that for a moment. Um, And I'll tell you that this is a good case of syncope, vasovagal syncope, which I'm sure all of you have encountered. The, the, um, the one feature of this case that I think draws it into question is that, that report of shaking or jerks. Um, and I think it's important to realize that, um, Syncope can oftentimes be associated with some myoclonic jerks, um, or even tonic-clonic appearing movements, um, but they, they usually only last a few seconds. Um, but we do see it in, you know, 10, 12% of patients who have syncope. So this is something that's been studied and reported and Just because someone has some jerking, um, due to a very transient period of, uh, cerebral hypoxia, that doesn't mean it's not syncope. It, it, it usually is still syncope. The other characteristics that help us, um, uh, distinguish between the two are the prodrome. Um, those with seizures will often have an aura that consists of a smell, a taste, an epigastric sensation, deja vu, visual symptoms, etc. For syncope, I think the prodrome is, is much more um classic and stereotyped. It usually involves the person feeling lightheaded. They may have palpitations, they'll feel hot and clammy, and they can report tunneling of vision, seeing dark spots, a graying out of vision. Um, Uh, syncope is much more likely to be positional. It often is associated with a low blood pressure and a low heart rate, whereas we often see the exact opposite in people who are having seizures. Um, asymmetric posturing and tongue lacerations are rare with syncope versus seizures. Um, and as we know, you can lose consciousness in, in both conditions, but, um, typically, those with syncope will have a much, uh, more rapid return to, to full awareness. Without any deficits. So a second case. This time, we have a, a 28-year-old woman. She presents to the ER with recurrent episodes of violent whole-body shaking. And in the ER she's witnessed have side to side thrashing movements of her head and her arms with forced eye closure. She frequently arches her back and has some pelvic thrusting quality to her movements, and the episodes last 5 to 10 minutes and have a waxing and waning quality. After the episode, the patient reports that she was fully aware throughout and she remembers a memory prompt that was presented by uh caregivers at the bedside during the episode. Her neurological exam after the episode is normal. So what's her likely diagnosis? Well, a lot of the features here are very classic for, uh, what we call psychogenic non-epileptic spells. This condition has a number of different names. Some people call them pseudo-seizures, some people call them, uh, non-epileptic seizures. In any case, this is a psychological condition, um, in which, uh, if you were to do an EEG, the brain's electrical activity is completely normal. Um, it's not something that people are doing intentionally. It's something people are doing unconsciously, um, uh, and it bears, uh, a close relation to somatiform or conversion disorder, um, as defined, uh, by psychiatry. So how do we tell the difference between these? Obviously, the gold standard uh for diagnosis would be EEG during the event. But if you're just hearing the story or seeing someone in the ER, some of the um features that will distinguish them are the duration. Seizures usually have a, a beginning, a middle, and an end, a crescendo and a decrescendo that lasts usually 2 minutes or less. Um, non-epileptic seizures can have a waxing and waning quality where people start having movements and stop and then start again. Um, those having seizures usually have their eyes open, whereas those with non-epileptic seizures have forced eye closure, as we talked about in the case, side to side head shaking, uh, or up and down head shaking, um, is much more common in non-epileptic seizures. We really just see no head movement or unilateral deviation of the head during an epileptic seizure. Um, back arching, pelvic thrusting, those are common movements. Uh, crying is much more common during a non-epileptic seizure. Um, and maybe the biggest giveaway in this case, uh, and in most cases that you'll hear about is, if you have whole body shaking and the person is retaining their awareness, it is much, much, much more likely to be a non-epileptic spell than Uh, an epileptic seizure. There are very rare epileptic seizures where people can have bilateral movements and still have retained awareness, but, you know, the vast majority of the time, you should be more suspicious of a non-epileptic event. Um, one other thing that people often tend to cling to is whether there's a history of abuse or trauma. We definitely think of these things as risk factors for psychogenic non-epileptic spells. However, um, unfortunately, um, people with epilepsy, um, are often the victims of abuse or trauma, um, sadly, and so, therefore, that history can be common in both populations and doesn't really distinguish as well as you might like. And I don't have a case for this, but seizure versus TIA is another question that comes up frequently. Transient ischemic attacks, um, the differences between them, I think are good to know. You know, with seizures, we are much more likely to see positive symptoms, meaning the presence of, uh, a sensation or a movement rather than the absence of a movement or sensation. And with TIA you're generally losing a function, so you'll have more negative symptoms and fewer positive symptoms. Maybe the most important thing distinguishing these two is the fact that seizures should be stereotyped, meaning that they're more or less the same experience for the patient each time. They may end differently depending on whether the seizure spreads to a larger part of the brain or not, but the beginning should be the same. With TIA what we're postulating is that a thrombus is traveling to some vessel in the brain, temporarily occluding it, and then, uh, uh, dissolving. And if that's the case, you know, it would take quite a unique mechanism for the same vessel to get repeatedly, um, uh, blocked off and then, uh, recantalized naturally. Um, producing the same symptoms each time. So, what I'm saying is that with TIA you don't get stereotyped events. If someone's having multiple TIAs, they're usually going to be different events each time. Um, loss of awareness is much more common with seizures than with TIA, um, and the duration is often much shorter with seizures versus TIA. So what are some of the key things that we need to think about or ask about when we're evaluating someone with a first-time seizure? Well, I think that um the points of emphasis in the history are a recent history of trauma, infection, um, or exposures um to drugs or alcohol. Um, you wanna know what the first behavioral change was because that helps us localize in the brain, the first symptom that patients experience in a seizure will often tell us where in the brain it started. Um, it's good to know if there's loss of awareness. That's important not just for, um, understanding what happened to the patient, but figuring out whether it's safe for them to drive, which we'll talk about. Um, you wanna know if there are any asymmetric features because that can sometimes help us lateralize where the seizures are coming from. Obviously, the duration, any postictal, meaning after the seizure, uh, deficits like a Todd's parsis where one side is weak contralateral to the side where the seizure started. Um, and you wanna know if they're back to their baseline. Um, the key components of the exam, I think, um, you know, a, a detailed neurological exam is always helpful but not really necessary or realistic, I think, um, for a non-neurologist. The main things you wanna know about are, does the patient have sustained nystagmus? Do the eyes keep beating in one direction only? Um, do they have pronator drift? Does one side tend to, you know, pronate or, or, um, the fingers curl, suggesting weakness on that side, or do they have slower finger taps on one side and fast finger taps on the other? Um, you can test this in kids with posting where you ask them to spin their arms and you'll find that one arm is just not moving as much as the other, suggesting weakness in that arm. And if they're ataxic, you know, if they're in off balance and, and not walking properly. Um, there are a number of labs that we typically get. I think you, you know all of these labs. I think a lumbar puncture is a good idea if you're suspicious for a CNS infection and there's no mass, uh, on imaging with a CT or MRI. And as far as imaging itself, a non-continent head CT is fine for screening, but ultimately, you need a, an MRI and we'll talk about that in a moment. It's important to file a confidential morbidity report if the patient lost awareness. We'll talk about that in a second, and I think referral to a neurologist is very reasonable after a first-time seizure. What about risk of recurrence? Well, there are certain risk factors that suggest that the first seizure won't be the last. Um, if they have a history of stroke or TBI, if the seizure happened out of sleep in the middle of the night, um, and then, of course, abnormal brain, uh, imaging or EEG, um, the odds of recurrence in the first two years range from 21 to 45% and that jumps to 45 to 65% if some element of the workup is abnormal. Um, usually, uh, that, that recurrence is gonna be within 2 years and 50% of the time it happens in the 1st 6 months. And the recurrence risk rises to 80% after someone has had two unprovoked seizures. So, um, that's why we, you know, very strongly recommend our patients start, um, receiving treatment if they have a second seizure. All right. So one of the big questions that you're always gonna get asked about and we always get asked about from patients is, can I drive? And um it's important to know the legal requirements. So, um, the California state law states that all physicians are legally required to file a confidential morbidity report, which is this form that uh you can find online, you just Google confidential morbidity report and the name of the city that you're in. Um, and you're supposed to send this to the local Department of Public Health if the patient has a condition that causes lapses of awareness. The same form, oddly is used for STDs, certain infectious diseases, so it's kind of a, a catch-all form, um, of things that the Department of Public Health wants to know about. Um, so, if you think that there's any chance that this person is gonna have another loss of consciousness or you're not sure, you should be filing this form. Oftentimes it's done in the ER, not always. Um, and then patients come to see us and then, um, you know, we're, we're the bad guy because no one else told them that they have to stop driving, but we do. Um, so anytime you can do that ahead of time, uh, that, that helps us out. Um, the Department of Public Health then forwards the, the form to the DMV and then the DMV sends the patient, um, the driver's medical evaluation, which is like a 10-page or eight-page form where they have to fill out the first page and then a physician is supposed to fill out the rest. Really, you only You have to fill out the section that's relevant for this patient. Um, so if it's a seizure or something like a seizure, there's just one small section you need to fill out and there's a, uh, an area where you can write a paragraph explaining the circumstances. Generally then, a patient will have their license suspended. And they need to be seizure-free for a minimum of 3 months according to California state law to be cleared. Um, and then, for some patients, you know, the neurologist will want to observe them for longer before clearing them to dry. Um, and we're happy to help with this process. We do this all the time. I would just say, you know, just be aware that legally, anyone, whether they're a neurologist or not, um, ER docs, primary care docs, whoever, are supposed to be filing these forms if you're Patient lost consciousness and you think it could happen again. Now, if it's something totally situational, you know, vasovagal syncope, uh, at a blood draw or something like that, I don't think it's necessary, but if it's a condition where you think it's going to happen again, um, you, you should file the form. OK. So, now turning to workup. So, um, we mentioned the EEG and uh the electroencephalogram is, you know, an ancient test by modern medical standards, but it's still super useful for us. It's good for, for understanding superficial cortical electrical activity. It's not great for Really deep structures. Um, the electrodes are placed on the scalp. This is looking top-down and these little circles represent where we put the electrodes across the head, um, and it records differences in electrical potential between electrodes or comparing the electrode to some reference electrode. The thing to know about it is that um it has a lot of limitations. First of all, it's very susceptible to artifacts. So, any sort of movement of the muscles of the face causes, you know, things like this that look really impressive but are all just muscle artifacts. We are trying to record something that is very low voltage, um, from the surface of the cortex. and that signal has to travel through uh the meninges, the skull, and the scalp to reach our electrodes. And so, as you can imagine, the muscles of the face, medical equipment around the patient, the movement of the heart and the chest, um, or bad electrode contacts or sweat, all of these things can cause artifacts that make the EEG very difficult to interpret. Secondly, it's very reader-dependent. So you may see different interpretations depending on where your patient is getting an EEG. Um, we have the benefit of, you know, doing EEGs all day every day, so we get a lot of practice and I think that, that helps the quality of our reads and then we've got, you know, a dozen other colleagues that we can turn to when we are stumped by an EEG. Um, and then it's also important to know that it's just a snapshot in time. So someone can have epilepsy and their EEG is totally normal on that day. Um, uh, there's a, there's some luck involved. The yield is, is just under 30%. Uh, sometimes if you do multiple EEGs or longer EEGs, that yield improves, but epilepsy is really a clinical diagnosis and the EEG helps us, but it doesn't make the diagnosis or if you rule it out. Um, imaging. So, the American Academy of Neurology recommends either a brain CT or an MRI for any unprovoked seizure. Um, a CT is what, you know, most patients are gonna get in the emergency room, and that's fine for gross structural lesions. So, you know, you can tell a patient, look, I'm pretty sure you didn't have a giant stroke or a big tumor, uh, or a bleed, um, and that's, you know, that's gonna be very reassuring. But there are a lot of smaller lesions that can only be picked up on MRI, you know, very small masses, tiny strokes, vascular malformations, um, an early neurodegenerative process like Alzheimer's disease, um, or scarring in the brain called mesotemporal sclerosis that sets people up for epilepsy after, usually after a febrile illness early in life. Um, and these are some examples of MRI findings in patients that I take care of. This is a cavernous malformation. Um, this is a patient here with, um, toxoplasmosis secondary to HIV which then caused mesotemporal sclerosis on the same side. This is where the hippocampus is and you can see it's very shrunken when you compare it to the other side. Uh, this is an example of a focal cortical dysplasia, um, an abnormality of neuronal migration, um, that caused, um, right frontal seizures for this patient. And then this is, uh, an example of a patient with a low-grade tumor, um, that caused their seizures. When in doubt, you know, if you have a patient, they need imaging, uh, you wanna sort of speed up the workup before they come and see a neurologist. Order a 3 Tesla epilepsy protocol MRI. If you use all of those words in the order, radiology will nail it almost every time at a, at any hospital. Um, not every hospital has a 3-Tsla scanner. I think, you know, we're, um, very lucky to have really good scanners and more importantly, really good neuroradiologists who can help us sort these things out, um, at UCSF. There are a number of different categories uh of, of seizures as we talked about before, you know, the primary categories are focal or generalized, and then you combine those different types of seizures into um uh different types of epilepsy, whether it's focal, generalized, combined, or unknown. And then those can then be um coalesced into epilepsy syndromes and the etiologies, as we said, can be, you know, um, as broad of a differential as you can imagine for almost any complaint or any disease. And as far as the syndromes go, you know, there is a huge number of epilepsy syndromes, a real laundry list, but I think there's only a few that um would be good for um those in um internal medicine or family practice or other types of primary care to, to really keep in mind. Um, really, I think there are 3 that you should, you should be aware of. One is childhood absence epilepsy, which usually happens in early childhood. Um, then there's juvenile myoclonic epilepsy, which can start in adolescence or have onset up to someone's late teens or early 20s. And then focal epilepsy, which can really strike at almost any age, but in younger people, might be due to, uh, uh, problems with uh malformations of cortical development or traumatic brain injury. And then in older people, um, traumatic brain injury, neurodegenerative diseases, malignancy, or stroke. So the etiologies may differ, but the end result is the same, and that's focal epilepsy. So we'll give you a couple of bullet points about each of these three syndromes very quickly. Childhood absence epilepsy. What's the stereotypical story or patient that you would hear about who has childhood absence. This would be a grade school child who has staring spells and inattention in school. And, um, when you, uh, uh, analyze the story further, you'll hear about 10 to 20-second episodes of unresponsive staring or blinking or eyelid fluttering. If it's an atypical absence seizure, they may go on to have a generalized tonic-clonic seizure, but that doesn't happen very often. Um, they may have a partial lapse in awareness or a complete lapse of awareness. Oftentimes, there's a genetic component. There may be a positive family history, and the EEG shows 3 Hz spike in wave. If you're ever doing any sort of board exam or recertification exam, it's highly unlikely anyone will show you an EEG, but if they do, it'll be 3 Hz spike in wave, an absence seizure, um, in which, you know, you see a spike followed by a wave, um, and it's 3 per second, meaning 3 Hz. Um, we can trigger this in the EEG lab with hyperventilation. So if you have a child blowing on a pinwheel continuously, you can see this, um, pattern and that makes the diagnosis. Um, and it can be treated with a number of drugs including ethosuccamide, valproic acid, and lamotrigine. Juvenile myoclonic epilepsy, the stereotypical story is the high school or college student who has early morning jerks or twitches followed by a tonic-clonic seizure. It usually happens during, you know, final exams week when they're sleep deprived or right after final exams when they've been drinking alcohol. And um that's the sort of stereotypical story for a presentation of JME. Um, myoclonic jerks refer to lightning-quick jerks involving one or more limbs. They're, you know, very, very fast. Um, and they may cause someone to drop an object or throw their phone across the room. Um, and that may be unexplained until they have a bigger seizure. Um, and those bigger seizures are tonic-clonic seizures. This too, um, has a genetic basis and has a similar appearance on EEG 3, but often at times up to 6 hertz spike in wave, um, and the patients may be photosensitive. So when you hear of someone having a seizure after strobe lights at a concert or a Pokemon video or something like that, that's this type of epilepsy in which we see it most commonly. It's very treatable, but unfortunately, you have to take medicines usually for life and valproic acid, lamotrigine, and levetiracetam are the most common. Case 3. So, a 31-year-old previously healthy right-handed man presents to clinic the day after a tonic-clonic seizure. He doesn't remember anything about the seizure. He was just told that it happened. His past medical history is known for a febrile seizure in early childhood, um, and no problems after that. On questioning, he reports a two-year history of monthly episodes of weird nostalgia in which everything around him seems familiar, as if he's seen the scene before. He also reports significant life stress of late as he is going through a contentious divorce. And his exam is notable for slowed finger taps and a flattened nasolabial fold on the right. EEG and MRI are pending. What's the likely diagnosis? Well, here, you know, we, the, the, you know, the cliche for writing a normal neurological exam in a chart is to say it's non-focal, right? Well, here, we've got a, uh, uh, an exam that's actually focal for a change and that's because this person has focal epilepsy. So, focal epilepsy, there really is not a stereotypical story or patient. The one I just gave you is an example, but not the example. Um, there's a huge range of ages, etiologies, and severities for focal epilepsy. Basically, it just means that the seizure is starting in one part of the brain and spreading from there. And the, the, the location of onset determines the symptoms. So for temporal lobe epilepsy, people will often have behavioral arrest, deja vu, which was the, the, um, experience that the patient in our case was, was describing, and automatisms. Um, for frontal lobe epilepsy, they often have very violent movements, hypermetoric movements out of sleep. Um, occipital, uh, lobe epilepsy often starts with visual phenomena and parietal lobe can start with somatosensory or mixed sensory modalities. And all can secondarily generalize and become tonic-clonic seizures, but they don't have to. The treatment duration is variable, but if there's a lesion on imaging, usually they're going to need longer treatment. And there are a lot of different treatments. I think lamotrigine, oxcarbazepine, and carbamazepine are the most common and kind of preferred drugs for this condition, although we're getting newer drugs every, you know, every year. Um, on the inpatient side, we may use loadable medications that you can really get a level quickly like phenytoin or levetiracetam. So the treatments I've already kind of alluded to, uh, medications are kind of the mainstay, but behavioral modification is important like avoiding alcohol or sleep deprivation. Um, surgery and neuromodulatory devices are sort of the cutting edge, uh, of the field, and diets for epilepsy, in particular, the, um, Uh, ketogenic diet or modified Atkins diet can often be helpful. Um, we don't have time to talk about all of those, but just to give you a sense of medications and how we use them, um, we have some drugs that are better for focal epilepsy. Things like phenytoin, carbamazepine, and oxcarbazepine. We have other drugs that are better for generalized epilepsy. For instance, for absence epilepsy, I mentioned ethosuximide earlier as the drug of choice. For infantile spasms, uh, a very rare type of epilepsy that affects, um, small babies, we have ACTH steroids, and vigabatrin. But there are a lot of drugs and most of the drugs that come on the market nowadays are considered broad-spectrum. They work for both types. Um, valproic acid, lamotrigine, levetiracetam, and topiramate. These ones in purple here, I think are the most popular drugs that you will see, uh, mentioned the most. But there's a long list of other drugs and that list is only growing. Most of the newer drugs have better side effect profiles. Most of them though, are not that much better in terms of efficacy. Some of the principles of medical management that we use and that I think are worth knowing. Maybe if I, if, if you only took one thing away from this talk, it might be this, treat the patient, not the drug level. So, I think it's common that we get drug levels in the outpatient setting just to see, you know, where Someone is at in terms of their Dilantin level or Keppra level or what have you. Um, and just because the level comes back high or supratherapeutic, doesn't mean that you need to change the dose. In fact, I would strongly encourage you to talk to a neurologist or epilepsy specialist before making any changes. Um, and that's because Patients outside of the normal range um may not have any signs of toxicity at all, and therefore, you don't necessarily need to make a change unless the patient has a clinical syndrome suggesting anticonvulsant toxicity. And that's usually gonna be things like diplopia, ataxia, extreme somnolence, dizziness, things of that nature. Um, a lot of anti-seizure medicines are enzyme inducers and therefore will have drug-drug interactions. Um, this is a, a chart that shows how certain anti-seizure medicines are metabolized and the take-home here is that topiramate, levetiracetam or Keppra, and gabapentin are the three that are, um, least hepatically metabolized, most renally metabolized, and therefore, least likely to have any drug-drug interactions. So, Unless your patient is on one of these drugs, be careful about um uh the interactions between anti-seizure medicines and other medicines you're prescribing. This is something we always check when we're meeting new patients. Um, if someone has had a breakthrough seizure, the things that you wanna ask about are infection, non-adherence, or medication changes, you know, where they put on something else that interacted with the seizure drugs. And then these last two are more for neurologists, but I think we try to push anti-seizure medicines to their highest tolerated dose before giving up on it and moving to another drug. So we don't like to have people on, you know, 3 low doses of medication, of different medications. We'd rather have them on 1 at a higher dose. And when we're switching anti-seizure medicines, there's usually a ramping process where we're increasing the new one before we decrease the old ones. There's usually a, uh, an overlap there that can be several weeks or even a couple of months. And we're switching medicines. OK. Case four. So, a 23-year-old previously healthy woman presents after a tonic-clonic seizure at 5:30 a.m. She recalls having twitches in her shoulders on getting out of bed, and then she lost consciousness and was found by her partner. This is her 3rd such episode in the past 2 years. Previously, an EEG showed generalized spike in wave and an MRI was normal. So this is a pretty classic story for juvenile myoclonic epilepsy, like we talked about. She's hoping to start a family in the next year and she's interested in starting an anti-seizure medicine. Which one of the following would be the worst choice? Valproic acid, levetiracetam, lamotrigine, or topiramate? And, you know, again, I don't think it's necessary for you to know about a ton of drugs, um, or a ton of facts about them, but I think it is important to know some of the adverse effects of the most popular ones. So, in this case, valproic acid would be the worst choice. And the reason why is the side effect profile for valproic acid, particularly for women of childbearing age, is pretty scary. It can cause teratogenesis, uh, in their offspring, uh, PCOS, weight gain, hair loss, osteopenia, pancreatitis, and hyperaminemia, which are admittedly, uh, relatively rare, but a long list of side effects. For phenytoin, gingival hyperplasia, peripheral neuropathy, and osteopenia. Lamotrigine rash, including Stevens-Johnson, which we'll talk about. Feroxxcarbazepine, it's hyponatremia, which can often be asymptomatic, but if it starts to get, you know, into the one-twenties, uh, it can be a problem. Levetiracetam, one of the most popular drugs, causes a very high rate of irritability, anger, and depression. Um, and for topiramate, weight loss, which some people are happy about, um, but also renal stones, cognitive slowing, and can be bad for people at risk for glaucoma. So, um, those are unique side effects for some of our most popular medicines, but almost all of our side effects can cause dizziness, diplopia, ataxia, and fatigue. And a couple more words on teratogenesis for valproic acid. The risk is thought to be about 8% based on uh pregnancy registries of having a major congenital malformation, that's things like spina bifida or cleft palate. Um, with most of our medicines, it's, it's much lower than that. And, um, the malformations happen in the first 4 weeks of gestation. So before a woman even misses a period, she, um, and, and knows she's pregnant, um, these things can happen. So, therefore, we often, um, prescribe folic acid, which mitigates this risk to any woman of childbearing age if there's any chance that they would become pregnant either intentionally or, or not. And going back to rash, so, um, you know, there are a lot of benign drug eruptions that can happen with a lot of these medicines, but the ones we're most concerned about are dress, which usually produces, you know, large areas of erythema that, um, can be pruritic or Stevens-Johnson syndrome, which can look similar but often is accompanied by blisters, joint pain, and fever. So, any of those things, it's good to involve a neurologist and a dermatologist ASAP. And to wrap up, um, I'll talk about when patients are medically refractory. What happens if all of these drugs don't work? Well, we've got lots of data that suggests that about 2/3 of patients will come, will become seizure-free on an anticonvulsant drug or some combination of anticonvulsant drugs. Once you get past the 3rd drug, the odds of becoming seizure-free are very, very low. So, if someone is on a 2nd or 3rd drug, they really should be seeing an epilepsy specialist to talk about what their options are. And getting to a comprehensive epilepsy center there is the key. Um, there's a big treatment gap. Lots of patients are never referred, unfortunately. Once they come and see us, we have the ability to localize seizures for those with focal epilepsy using a combination of EEG, high-quality MRI. PET scans, magnetoencephalography, SPECT scans, um, and with invasive intracranial electrodes. Um, these can be used to help us design, um, a resection or implantation of a neuromodulatory device that can really be life-changing for our patients. And those surgical treatments again, resection, we have laser ablation which is minimally invasive, um, and devices that are essentially neurostimulation devices that can gradually reduce the number of seizures patients experience. We have a huge team. Uh, we're very fortunate in that regard. We have epileptologists, both, um, adult and pediatric. We have a number of outstanding nurses and nurse practitioners who have been with us for a long time. We have a fantastic surgeon. Edward Chang on the adult side and Curtis August on the pediatric side who, um, I think do a phenomenal job and are really dedicated to their patients. And we have outstanding fellows. Um, we're very lucky to have really great trainees, uh, coming through every year. Um, and so with that, I think I'll stop and see if we have any questions.
