23-year-old (Female) with Epilepsy

00:01 Okay, guys really high-yield but hard question here.

00:07 Let's buckle down and let's focus on this one, it gotta require all of our brain cells.

00:12 So, we have a 23-year-old woman who presents to the office for a checkup.

00:17 The patient has a 5-year history of epilepsy with focal onset motor seizures and she is currently seizure-free on 50 mg of lamotrigine taken 3 times a day.

00:31 She does not have any concurrent illnesses and does not take any other medications except for contraceptive pills.

00:39 She is considering to become pregnant and seeks advice on possible adjustments or additions to her epilepsy therapy.

00:48 Which of the following changes should be made in the patient's treatment? Answer choice A: Decrease the dose of lamotrigine to 50 mg twice a day; Answer choice B: Recommend intake of 5 mg of folic acid daily with no changes to antiepileptic therapy; Answer choice C: Recommend intake of 100 micrograms of vitamin K daily with no changes to antiepileptic therapy; Answer choice D: Switch lamotrigine to oxcarbazepine prior to conception; or Answer choice E: No changes or addition to the patient's regimen are required Take a moment to come to the answer choice yourself before we go through it together.

01:44 Okay, like I was warning you guys when we started, this is a hard question but it's important.

01:50 These kinds of questions commonly come up on the USMLE because they really like testing your ability to eliminate answer choices through thinking, as opposed to simply knowing the answer and this is that kind of question. You're not expected to know.

02:07 This is like advanced ward-level neurologist question but you can figure it out for USMLE because you can deduct with your reasoning how to come up to the answer and that's why these questions show up on the exam.

02:20 They are testing your thinking skills. So let's do it together.

02:24 Now, let's look at the question characteristics. This is an OB-GYNE question.

02:28 We have a woman coming up who wants to have pregnancy but she happens to have epilepsy, this goes to OB-GYNE.

02:35 Now it's a one-step question.

02:37 How do you manage the medication for this person who wants to become pregnant who happens to have epilepsy? Of course, the stem is required.

02:46 All the information we're going to pull is from the question stem so let's walk through it.

02:50 The first thing we have to do here is we have to figure out what is going on with her medical condition to give her recommendations.

02:58 So we have a young female patient and she's here for a pre-pregnancy consultation.

03:04 We're told that she has a history of epilepsy and we are knowing that the seizures are actually, thankfully, well-managed on taking lamotrigine three times a day.

03:16 Now, it's very, very important to understand that epileptic seizures are a significant risk during pregnancy.

03:25 When a person is seizing they can fall so that gives risk to both the embryo and fetus and the mother if she happens to have a seizure and fall.

03:33 Also, oxygen supply can be cut off during seizure and that's another risk to the pregnancy and to the mother and fetus.

03:44 Thus, we have to give anti-seizure medications to prevent epileptic seizures in pregnancy but the thing is, these medications have different teratogenic risk potentials.

03:58 So, all medications, of course, have some degree of teratogenicity but some have less than others which is how we decide what to give pregnant women when they have a history of epilepsy.

04:10 Now, they have been quite clever in this question.

04:14 They don't push you too hard because you can do that on USMLE and they actually picked lamotrigine which has the lowest teratogenicity potential for pregnancy and epilepsy.

04:26 Now, in addition to its low teratogenicity, it has been working well and the patient has been able to tolerate it.

04:35 So from simple test-taking strategy, you don't want to switch the medication or switch the dose because it has been working well for the patient.

04:44 So we could even eliminate right at this point answer choices A and D because they want to decrease the dose or switch it to another agent.

04:53 If the patient is tolerating a medication well and they are seizure-free, don't mess with it.

05:00 Leave the dose, leave the medication.

05:02 Being seizure-free is very important so that's what they're testing here right off the back.

05:07 Do you understand that concept? It if it isn't broke, don't try to fix it.

05:12 Folic acid though is recommended for all women, whether they have epilepsy or not, who want to become pregnant right and that's to prevent neural tube defects.

05:23 Taking anti-seizure medications has been shown to decrease folate levels.

05:29 So, outrageously important, we actually give higher folic acid supplementation in women who take anti-seizure medications.

05:39 So if a woman comes in and she wants to be pregnant, we put her on 0.4 mg daily of folic acid but if they want to get pregnant and they take anti-seizure medications, then we want to bump that from 0.4 mg to 5 mg daily to prevent neural tube defects because again, women should be supplemented with folic acid but in the setting of antiepileptic medications which can lower folic acid, we want to supplement even more.

06:11 With respective vitamin K, there really is limited evidence for the use of vitamin K in pre-pregnancy.

06:17 You can use vitamin K postnatally for newborns to prevent hemorrhagic disease of the newborn but it's not something you give the mom and that's put it there to try to throw you off and confuse you to mix you up about pregnancy and newborns.

06:33 So, here really, the answer choice that's correct is answer choice B, you want to actually just simply recommend the intake of 5 mg of folic acid with no change in her antiepileptic regimen.

06:46 Now, let's go through that a little bit more to explain why we don't want to change things.

06:51 This patient takes lamotrigine which is an antiepileptic drug that has a low teratogenic potential.

06:59 Now lamotrigine is a second-generation antiepileptic drug.

07:04 It works by inhibiting voltage-gated channels and also it has some blocking NMDA receptors.

07:10 Overall, this decreases neuronal firing to decrease seizure occurrence.

07:16 Now, the consensus here is that uncontrolled epilepsy poses a higher risk for the mother and the fetus so we don't want people to be having seizures.

07:27 We want to give them antiepileptic therapy to get seizure control.

07:32 Now, lamotrigine is an FDA category C medication.

07:38 Now, category C means that animal studies have shown that there is teratogenic potential but low but there's no human studies to support these findings.

07:49 When choosing a medication in a woman of childbearing age, we want to pick the one with the lowest teratogenic potential because the woman is of childbearing age.

08:01 Now, lamotrigine, thankfully, has a 2-3% teratogenic potential and this is actually less than other medications which have a 5-10% teratogenic potential such as valproic acid.

08:15 Now, when looking at guidelines for epilepsy in pregnancy, folic acid is recommended for all women who want to become pregnant, epileptic or not, because you want to decrease the rate of neural tube defects but antiepileptic drugs can decrease your folic acid even more.

08:35 So for these patients, we want to really supplement the folic acid to prevent the neural tube defect possibility.

08:41 Now, in animal studies, lamotrigine has been shown to decrease folate levels in rats.

08:47 Though we don't have human studies to collaborate here, the recommendations even more reasonable because we have some animal studies to support us. So we don't want to change the dosing and regimen because she is seizure-free on her regiment and the important learning point here, and they want you to understand is that you give folic acid for women who want to become pregnant and antiepileptic drugs lowered even more so you want to give a higher dose of folic acid.

09:14 Don't mess with the seizure medications if they're working for the patient.

09:18 Let's look at some of the other answer choices and figure out why they are wrong.

09:24 Answer choice A, decrease the dose of lamotrigine to twice a day from three times a day.

09:29 Now, what you want to do when giving seizure medications is give the lowest dose that gives you adequate seizure control.

09:37 Now, this patient is seizure-free with a 50 mg dose three times a day.

09:42 What ends up happening is that in pregnancy, you have increased blood volume and you also had increased hepatic function.

09:50 So blood concentration of many medications actually decreases so we definitely don't want to decrease seizure medication dosing cuz that will put you at an even higher risk of seizure.

10:00 So based on even that rationale, you can eliminate that answer choice.

10:05 Now, answer choice C which is the recommendation of adding vitamin K.

10:09 Well, there are some tricks to this but it's wrong and here's why: now, antiepileptic drugs that induced hepatic enzyme function such as phenobarbital and phenytoin had been associated with vitamin K deficiency- bleeding disorders in newborns but there isn't sufficient evidence to support the use of vitamin K supplementation in all women who have epilepsy to prevent this condition.

10:35 So really vitamin K administration is really postnatal for a possible condition that's called the hemorrhagic disease of the newborn and that's really there to confuse you.

10:46 We don't use it in seizure.

10:48 We don't use it in the mother.

10:50 It's for the fetus.

10:51 Now, answer choice D, where you can switch from lamotrigine to oxcarbazepine.

10:58 Oxcarbazepine is another second-generation antiepileptic drug that has a relatively low teratogenic potential but again, there is no benefit from switching an agent even if they're similar low teratogenic potential if the current medication the patient is taking is working.

11:15 That's what they expect you to know.

11:17 You don't have to be board certified neurologist to know when to switch from lamotrigine to oxcarb for USMLE but you should understand if the current regimen is working, don't change it.

11:28 Now, answer choice E, which is don't change anything. Now that's true, we don't want to change the antiepileptic drug.

11:36 However it is important to know and every doctor should know this, we give folic acid to prevent neural tube defects in women who want to become pregnant and we give the even higher dose in women who take antiepileptic drugs.

11:49 Now, let's review some high-yield facts. High-yield epilepsy in pregnancy.

11:55 Now, pregnant women with epilepsy are considered high-risk pregnancies and these are usually cared for by a high-risk obstetrician.

12:04 Now, the trade-off between seizure control and teratogenicity of medication is really what we're balancing.

12:10 We want to prevent seizures cuz that can be very dangerous to the mother and the fetus but at the same time, we don't want to give a medication that's, you know, going to cause any teratogenicity significantly to the fetus.

12:23 Now, the best antiseizure medication during pregnancy is really one that provides good seizure management to the patient and has the lowest teratogenic potential possible.

12:33 Now, if you look at our picture here where we have a high to low gradient of teratogenicity in various medications, you'll see lamotrigine is there on the very low end and valproic acid is on the very high end.

12:46 Really important to understand the top highest one and the lowest one as those are most likely to be tested on USMLE.

12:53 Those in the middle are much more advanced.

12:55 Important to know but I want you to really pay attention for the outliers because those are commonly tested.